Dementia amp Alzheimerrsquos Research

in Puerto Rico

Ivonne Z Jimeacutenez-Velaacutezquez MD FACP

1066 Puerto Rico Delegate

Chair Department of Medicine

School of Medicine

University of Puerto Rico

29st ADI International Conference San Juan PR May 2 2014

Puerto Rico

Agenda

Puerto Rico

Geographics amp Demographics

Genetic Influence Familial Study (2002-2014) Columbia University Sergievsky Center

LOAD

EOAD

1066 Dementia Cohort Study (2006-2014)

Institute of Psychiatry London UK

Prevalence Phase ndash N = 2000

Incidence Phase ndash N= 1265

Description

Caribbean island conquered by the Spanish - 1492

After the war - became part of USA ndash 1898

Commonwealth - 1950

Population - 37 million people

14 over 65 yo

Principal language ndash Spanish

Second language - English

Primary mortality causes - PR

1- Heart disease

2- Cancer

3- Diabetes Mellitus

4- Alzheimerrsquos disease

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Puerto Rico

Agenda

Puerto Rico

Geographics amp Demographics

Genetic Influence Familial Study (2002-2014) Columbia University Sergievsky Center

LOAD

EOAD

1066 Dementia Cohort Study (2006-2014)

Institute of Psychiatry London UK

Prevalence Phase ndash N = 2000

Incidence Phase ndash N= 1265

Description

Caribbean island conquered by the Spanish - 1492

After the war - became part of USA ndash 1898

Commonwealth - 1950

Population - 37 million people

14 over 65 yo

Principal language ndash Spanish

Second language - English

Primary mortality causes - PR

1- Heart disease

2- Cancer

3- Diabetes Mellitus

4- Alzheimerrsquos disease

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Agenda

Puerto Rico

Geographics amp Demographics

Genetic Influence Familial Study (2002-2014) Columbia University Sergievsky Center

LOAD

EOAD

1066 Dementia Cohort Study (2006-2014)

Institute of Psychiatry London UK

Prevalence Phase ndash N = 2000

Incidence Phase ndash N= 1265

Description

Caribbean island conquered by the Spanish - 1492

After the war - became part of USA ndash 1898

Commonwealth - 1950

Population - 37 million people

14 over 65 yo

Principal language ndash Spanish

Second language - English

Primary mortality causes - PR

1- Heart disease

2- Cancer

3- Diabetes Mellitus

4- Alzheimerrsquos disease

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Description

Caribbean island conquered by the Spanish - 1492

After the war - became part of USA ndash 1898

Commonwealth - 1950

Population - 37 million people

14 over 65 yo

Principal language ndash Spanish

Second language - English

Primary mortality causes - PR

1- Heart disease

2- Cancer

3- Diabetes Mellitus

4- Alzheimerrsquos disease

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Primary mortality causes - PR

1- Heart disease

2- Cancer

3- Diabetes Mellitus

4- Alzheimerrsquos disease

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

ldquoENFERMEDAD FAMILIAR INFLUENCIA GENETICA ALZHEIMERrdquo (EFIGA)

Genetic Influence Family Study

LOAD EOAD

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

History

1989 ndash Studying Latino families ndash in NY

Found double risk in Caribbean patients ndash PR DR

Islands considered geographic isolates Migration predominantly out of country

No risk factors could explain differences in disease

rates

PSEN1 PSEN2 SORL1

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Methods

Since June 2002 a cohort of Caribbean Hispanics from

PR with familial late and early-onset AD have been studied after IRB approval was obtained

Identified examined and collected blood samples from gt 1300 individuals of gt 350 families affected with the disease

Studies done at the Clinical Research Center University Hospital Puerto Rico Medical Center or at patientrsquos homes

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

EFIGA Research Study

Neuropsychological Evaluation

Physical Neurological Examination

Blood tests genetic testing and APO-E

Socio-Demographic and Risk Factor Interview

Clinical Interview

Informant Interview (if applicable)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Neuropsychological Tests

Memory

Selective Reminding Test Benton Recognition

Orientation Test

Language

Boston Naming Control Fluency Letter Category Fluency Test Sentence Repetition Comprehension

Abstract Reasoning

Similarities IdentitiesOddities

Construction

Rosen Figure Test Benton Matching Test Attention

Cancellation Test (ShapeTMX)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Early Onset

Familial Genetic Study

2007 ndash 2014 ndash largest cohort of EOAD

gt 150 families identified in PR

15 - 40 ndash 49 yrs

537 ages 50 ndash 59 yrs

40 PSEN1

100 carriers have Gly206Ala mutation

West side more clusters - common ancestor

Study ongoing

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Early Onset

Familial Genetic Study

Gly206Ala mutation

Associated with a mean age of onset of 56 years

ranging from 47 years to as late as 70 years

Presentation

Increased seizures

Increased hallucinations

Fully penetrant

Age at onset is not modified by ApoE genotype

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Identification of Novel Loci for Alzheimer Disease and Replication of CLU PICALM and BIN1

in Caribbean Hispanic Individuals Arch Neurol Nov 8 2010

Lee JH Cheng R Barral S Reitz C Medrano M Lantigua R Jimeacutenez-

Velaacutezquez IZ Rogaeva E St George-Hyslop PH Mayeux R

Cheng Barral Reitz Lantigua and Mayeux) Gertrude H Sergievsky Center (Drs Lee and Mayeux) and

Departments of Neurology (Drs Barral Reitz and Mayeux) Psychiatry (Dr Mayeux) and Medicine (Dr

Lantigua) College of Physicians and Surgeons and Department of Epidemiology School of Public Health

(Drs Lee and Mayeux) Columbia University New York New York Universidad Tecnoloacutegica de Santiago

Santiago Dominican Republic (Dr Medrano) Department of Internal Medicine University of Puerto Rico

School of Medicine San Juan Puerto Rico (Dr Jimeacutenez-Velaacutezquez) Centre for Research in

Neurodegenerative Diseases Departments of Medicine Laboratory Medicine and Pathobiology and

Medical Biophysics University of Toronto and Toronto Western Hospital Research Institute Toronto Ontario Canada (Drs Rogaeva and St George-Hyslop) and Cambridge Institute for Medical Research and

Department of Clinical Neurosciences University of Cambridge Cambridge England (Dr St George-

Hyslop)

Family

Exome Selected Individuals

230-21 Age of onset = 47

230-24 Age of onset = 70

Age at onset varies widely

Exome Selected Individuals

458-5 Age of onset = 43

458-52 Age of onset = 64

El Velorio (Baquineacute) de Francisco Oller

Early Onset AD

Descriptive profile N = 147 individuals affected

with the Early Onset Alzheimerrsquos disease in

Puerto Rico (Gly206ala mutation)

EOAD in PR

58

42

0

10

20

30

40

50

60

70

Female Male

Individualrsquos Gender

N= 147

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Age at onset varies widely

Exome Selected Individuals

458-5 Age of onset = 43

458-52 Age of onset = 64

El Velorio (Baquineacute) de Francisco Oller

Early Onset AD

Descriptive profile N = 147 individuals affected

with the Early Onset Alzheimerrsquos disease in

Puerto Rico (Gly206ala mutation)

EOAD in PR

58

42

0

10

20

30

40

50

60

70

Female Male

Individualrsquos Gender

N= 147

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

El Velorio (Baquineacute) de Francisco Oller

Early Onset AD

Descriptive profile N = 147 individuals affected

with the Early Onset Alzheimerrsquos disease in

Puerto Rico (Gly206ala mutation)

EOAD in PR

58

42

0

10

20

30

40

50

60

70

Female Male

Individualrsquos Gender

N= 147

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Early Onset AD

Descriptive profile N = 147 individuals affected

with the Early Onset Alzheimerrsquos disease in

Puerto Rico (Gly206ala mutation)

EOAD in PR

58

42

0

10

20

30

40

50

60

70

Female Male

Individualrsquos Gender

N= 147

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

58

42

0

10

20

30

40

50

60

70

Female Male

Individualrsquos Gender

N= 147

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

15

54

31

0

10

20

30

40

50

60

40-49 50-59 60-65

Age Group

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

673

136

27

143

2 0

10

20

30

40

50

60

70

80

Married Widowed Never Married Divorced Separated

Marital Status

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

171

62

137

275

186

76

0

5

10

15

20

25

30

Some Primary Middle Secondary College gt College

Education Level

Some

Primary

Middle

Secondary

College

gt College

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

151

34

185 144

96 96

281

14 0

5

10

15

20

25

30

Occupation

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

EOAD in PR

748

07 07 5 58 65

29 36

0

10

20

30

40

50

60

70

80

First Symptom

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

1 5

6 5

7

10

4 15

5 4

22

4 9

3

Related Diseases Liver Disease

Peptic Ulcer

PVD

Stroke

Head Injury

Seizure

Cancer

Arthritis

Myocardial Infraction

Other Heart Disease

Hipertension

Thyroid disease

Diabetes

Pulmonary Disease

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Toxic Habits

19

27

3

0 5 10 15 20 25 30

Alcohol Use

Smoking

Illicit Drug

N

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

APOE4 in Puerto Rico

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

APOE4 in Dominican Republic

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Western Region

Individuals

Mayaguez 41 Aguadilla 27 Isabela 17

Southern Region

Individuals

Coamo 15 Ponce 11 Yauco 10

Northern Region

Individuals

Carolina 30 Camuy 26 Vega Baja 13

Eastern Region

Individuals

Caguas 60 Barranquitas 23 San Lorenzo 19

N=396

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Acknowledgments

Genetic Study

Funding Columbia University-NIH

Fidelity Foundation

Health Innovation Award

Best Clinical Investigation

Merck Co Sept 2009

EFIGAEOAD members Richard Mayeux MD - PI-NY

Rafael Lantigua MD

Martin Medrano MD

Joe Lee PhD

Vincent Santana MS

Maribella Gonzalez PhD

Lydia Robles MS

Aleyda Maldonado PhD

Ivonne Z Jimeacutenez MD-PI-PR

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

The Next Steps ndash DIAN Study - 2014

bull The Dominantly Inherited Alzheimer Network

(DIAN) ndash Prevention Trial

bull International research partnership of leading

scientists determined to understand a rare

form of Alzheimerrsquos disease that is caused by a gene mutation

bull Understanding of this form of Alzheimers

disease may provide clues to decoding other

dementias and developing dementia

treatments

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

More and more studies suggest that lifestyle

changes may be able to silence the

expression of risk genes a phenomenon

called epigenetics

ICAD Epigenetics

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

The 1066 Puerto Rico

Dementia Prevalence Study

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Prevalence studies worldwide

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Bayamoacuten Puerto Rico

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

The 1066 research studies

Doorknocking at catchment area

Cognitive test

Clinical interview

Socio-demographic and risk factor interview

Physical neurological examination

Blood tests

Informant interview

1066 research studies

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

1066 Puerto Pico Prevalence Study-Data December 2006 ndash June 2009

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Gender N=2000

321

679

0

10

20

30

40

50

60

70

80

Male Female

Percent

Percent

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Age Group

21 23 24

32

0

5

10

15

20

25

30

35

65-69 70-74 75-79 80+

Age Group

Percent

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Marital Status

0

10

20

30

40

50

62

486

334

119

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Occupation

650

319

17 11 02 00

100

200

300

400

500

600

700

800

900

1000

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Level of Education

2

13

19

39

27

None

Some (did not complete primary)

Completed Primary

Completed Secondary

College

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Daily Habits

0

5

10

15

20

25

30

35

40

45

PhysicalActive

Fairly Not Very Not at all

18

426

267

127

827

173

no

yes

Smoking

Physical Activity

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Have you ever been a heavy drinker

54

46

40

42

44

46

48

50

52

54

56

Yes No

Percent

Percent

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos NutritionDietary Findings

0

10

20

30

40

50

60

70

80

Never SomeDays

MostDays

EveryDay

49

546

224 181

221

764

15 0

Meat

Fish

Frequency of Eating Meat and Fish Servings of Fruit and Vegetables in the last 3 days

89

149

344 329

32 48 08

02

0

5

10

15

20

25

30

35

40

0 1 a 2 3 a 4 5 a 6 7 a 8 9 10 a 12 15-22

Never 99

Some Days 1

Frequency of Hunger Through Shortage of Food

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Household Characteristics

01

999

0

20

40

60

80

100

no yes

Water in household

03

997

0

20

40

60

80

100

no yes

Plumbed bathroom in

household

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

0

10

20

30

40

50

60

70

High Blood Pressure Diabetes Heart Problem Stroke

692

433

253

85

Participantrsquos Health Findings

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Frequency of Participants with Private Insurance

9580

420

no yes

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos Need for Care

0

10

20

30

40

50

60

70

80

90

Needs CareSome of the

Time Needs CareMuch of the Time

Does Not NeedCare

49

99

853

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Participantrsquos social network typology

1670

54

11 10 9

0

10

20

30

40

50

60

family

dependent

locally

integrated

locally self-

contained

wider

community

focused

private

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Prevalence of Dementia Case Identification N=19262000

DSM IV Dementia Diagnosis

Education Adjusted 1066 Lancet

Dementia Diagnosis

Non-Case 954 883

Case 46 117

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Prevalence of 1066 and DSM IV

Dementia

DSMIV0

2

4

6

8

10

12

DSMIV

1066

Rodriguez et al Lancet 2008

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Prevalence of Depression Case Identification

ICD 10 Depressive

Diagnosis

DSM IV

Depression

Diagnosis

GMSAGECAT

Depression

Diagnosis

Case 18 8 221

PR data from December 2006 through July 2008

Past History of Depression

Yes 215

No 785

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Prevalence of Dementia Case Identification 08 CSIrsquoD cog itive

Score

CSIrsquoD Discri i a t

Function Score

Non - Case 643 863

Possible Case 122 22

Probable Case 234 116

PR data from December 2006 through July 2008

Lancet

1066 Dementia

Diagnosis

Education

Adjusted Lancet

1066 Dementia

Diagnosis

DSM IV

Dementia

Diagnosis

Non-Case 889 884 942

Case 111 116 58

PR data from December 2006 through July 2008

Family History of Dementia

Yes 202

No 788

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 Incidence Study (2011-2013)

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 Cohort Study

bull Baseline cohort (N=2000) interviewed 2006-2009 - revisited

bull Follow-up (2011-2013)

ndash Re-interviewed 1268 (631)

ndash Deceased 299 (149)

ndash Refused not traced 442 (220)

ndash 6327 person years of follow-up

bull Dementia free cohort (n=1765)

ndash 1388 (887) follow-up to death or re-interview

ndash 5509 person years of follow-up

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

0

10

20

30

40

50Incid

en

ce 1

000 P

YR

DSMIV

1066

Incidence of 1066 Dementia and DSM-IV dementia (per 1000 person years)

Prince et al Lancet 2011

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico - Incidence of 1066 Dementia (per 1000 person years) by age and gender

0

10

20

30

40

50

60

65- 70- 75- 80+ All ages

Female

Male

Combined

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Sociodemographic factors and 1066 dementia risk

1066 (meta-analysis) Puerto Rico

Age (per 5 year band) 167 (156-179) 190 (155-234)

Gender (M vs F) 072 (061-084) 081 (055-120)

Education (per level) 089 (081-087) 090 (076-109)

Assets (per asset) 093 (088-100) 125 (069-227)

Cognitive reserve

Animal naming 093 (091-094) 088 (083-092)

Literacy 068 (055-084) 055 (030-102)

Prince et al Lancet 2011

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 cohort study Factors independently associated with

mortality

Hazard ratios

Age (per 5 year band) 148 (130-168)

Gender (M vs F) 138 (109-173)

Education (per level) 087 (079-096)

1066 dementia 297 (227-387)

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 cohort study Anaemia and 1066 dementia risk

Prevalence Proportional sub-

hazard ratio

Anaemia 322 132 (088-197)

Hb 091 (071-104)

No anaemia 1 (ref)

Microcytic

anaemia

24 198 (066-594)

Normocytic 291 130 (086-197)

Macrocytic

anaemia

08 Too few cases

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 cohort study Thyroid function and 1066 dementia risk

Exposure Prevalence Proportional sub-

hazard ratio

Thyroid stimulating

hormone (TSH)

Per SD 084 (074-097)

Normal TSH 817 1

Sub-clinical elevation 51 069 (025-195)

Clinical elevation 133 052 (026-105)

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 cohort study Micronutrients and 1066 dementia risk

Exposure Prevalence Proportional sub-hazard ratio

Vitamin B12

Per SD 105 (088-127)

Low B12 89 084 (041-174)

Folate

Per SD 101 (083-123)

Low folate 53 066 (020-212)

Homocysteine

Per SD 099 (081-121)

Normal homocysteine 642 1

Mild elevation 332 102 (065-158)

Moderate elevation 26 076 (019-304)

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Puerto Rico 1066 cohort study Diabetes and 1066 dementia risk

Exposure Prevalence Puerto Rico

Diabetes 412 097 (066-143)

By diabetes control

No diabetes 588 1 (ref)

Detected controlled 103 087 (045-170)

Detected not controlled 213 125 (081-193)

Not detected not controlled 96 049 (020-122)

Glucose

per SD 117 (098-140)

Haemoglobin A1c

per SD 123 (103-147)

Normal 248 1 (ref)

At risk for diabetes 455 108 (066-176)

Elevated 297 117 (070-197)

Metabolic syndrome 681 082 (055-122)

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

The Next Steps

bull 10 66 Third wave

bull Dissemination Dissemination Dissemination

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Donrsquot forget

Sunday morning

1066 Satellite Symposium

on Risk Factors

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

Acknowledgments 1066 Study

Support

Bayamon Major Ramon Luis Rivera and Staff

Funding Puerto Rico Government

Grant ndash Legislature (2006-2014)

Pfizer Company

Welcome Trust ndash Third phase

PR 1066 Team Members

Maribella Gonzalez PhD Gilberto Ramos PhD Jose Carrion-Baralt PhD Josefina Groennau MS Iris Violeta Lugo BS Maria Lugo BS Rosalina Maldonado BS Lydia Robles MS Juan Gonzalez MD Cristina Ramos MD Emmanuel Cruz MD Frankie del Olmo MD Gilberto Perez MD Wendy Matos PhD Ivonne Z Jimeacutenez MD - PI

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull

ldquoY y

rsquo w y

if your work

i rdquo

Emil Kraepelin

bull