THE LINKS BETWEEN LIFESTYLE AND DEMENTIA

Professor Laurie Brown

National Dementia Congress, 20 February 2014,

Melbourne

• Provide an overview of key risk factors and understanding the difficulties in measuring and interpreting risk

• Look at impact of smoking, physical activity and BMI on risk of dementia

• Look at impact of trends in midlife BMI on dementia in latelife

• Consider the association of dementia with diabetes

AIM-OUTLINE

3

Background

• Number of Australians with dementia is expected to more than double by 2030 as is the cost of providing care.

• Population ageing is often considered the most important factor determining the occurrence of dementia in the future

• Projections of dementia cases are therefore often based solely on the projected age composition of the population.

● from under 200,000 persons in the year 2000, to over 300,000 by the early 2020s, and rising to approximately 500,000 in the 2030s

4

Background cont.

• Emerging evidence for the role of modifiable risk factors in dementia - reduce the disease burden by reducing risk, delaying onset and/or by early intervention to modify disease progression.

• As more intervention options become available, policy makers will need decision-support tools that allow them to evaluate and compare the likely health and economic outcomes of these strategies to identify the most cost effective approaches at a population level.

Development of a computer model that simulates the health and economic impacts of dementia prevention strategies.

• DCRC – Early Diagnosis & Prevention

• DYNOPTA

• Alzheimer’s Australia

• Literature – epidemiological studies

Background – The Evidence Base

Protective Factors Risk Factors Cognitively stimulating activities (across the lifespan)

Age

Regular physical activity Genetic factors e.g. Apolipoprotein E

status, Down syndrome

Higher engagement in leisure/social activities

Family history

Higher education Under & overweight, obesity

Light-moderate alcohol intake

Cardiovascular risk factors e.g. smoking, hypertension, elevated cholesterol, high intake of saturated fat

Diet e.g. Fish intake Diabetes, stroke, heart disease

Traumatic brain injury

Depressive symptoms

Background – Risk (and Protective) Factors

• Barnes et al (2013) estimated that 13% of AD cases are potentially attributable to physical inactivity

• High levels of physical activity were associated with a 38% lower risk of cognitive decline in older people and low to moderate levels of physical activity with 35% lower risk of cognitive decline, compared to those who were sedentary (Sofi et al, 2011)

• A 28% reduced risk of any dementia and 45% reduced risk of AD for those in the highest physical activity category compared to the lowest (Hamer & Chida, 2009)

• Exercising at least twice a week at midlife was associated with a 52% reduced risk of dementia at age 65-79 years (Rovio et al, 2005)

Example - Dementia & Physical Activity

• Changing list

• Modifiable

• Beneficial at a population level – not necessarily so for each individual

• All types of dementia (Alzheimer’s disease ~ 60%, vascular dementia ~

20%)

• Reduce the risk of dementia and/or delay onset

• Selection effects e.g. alcohol drinkers

• Non-linear effects e.g. U-shaped relationship for alcohol or BMI

• Mid vs late life e.g. obesity, chol

• Interactions e.g. lifestyle with APOE, joint distributions

Background – Understanding Risk (and Protective) Factors

• Build brain reserve (allowing normal cognitive function to continue for longer)

• Reduce protein accumulations

• Effects on brain health – reducing inflammation, increasing brain blood flow, growth of new neurons and synapses

• Benefits for other health factors related to cognitive functioning – vascular conditions, diabetes and depression.

MECHANISMS

• To develop a cell-based cohort (dynamic-longitudinal) model to project the impact of modifying risk factors on dementia at a population level

• Process

● Collect data (often cross-sectional available)

● Create synthetic (5yr age-sex) cohorts & generate projections

● Get risk estimates for dementia

● Model trends in risk factors

● Project future risk factor profile in age-sex cohorts

● Estimate proportions of older people having a history of midlife or latelife risk factor (X)

● Model dementia numbers by risk factor categories

NATSEM (DCRC-EDP) Dementia Prevention Model

PREVALENCE OF DEMENTIA

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Ageing of Australia's Population (next 45 years)

Australia 2006

Male Female

200000 100000 0 100000 200000

0

10

20

30

40

50

60

70

80

90

100+

Australia 2051

Male Female

200000 100000 0 100000 200000

0

10

20

30

40

50

60

70

80

90

100+

13

Age-specific Prevalence Rates of Selected Risk

Factors

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

85+

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

85+

Male Female

Ever smoked

BMI>=30

Sedentary

14

Relative Risk of Dementia

• Ever smoked vs never smoked 1.140

• Obese vs non-obese 2.296

• Sedentary vs active ` 1.693

15

Projected Numbers of People Living With Dementia Considering Ageing Only

-

100,000

200,000

300,000

400,000

500,000

600,000

700,000

2006 2011 2016 2021 2026 2031 2036 2041 2046 2051

Nu

mb

er

of p

ers

on

s w

ith

de

me

ntia

Male

Female

16

Impact of Reducing Smoking

-4.0%

-3.0%

-2.0%

-1.0%

0.0%

2006

2011

2016

2021

2026

2031

2036

2041

2046

2051

Per

cent diff

ern

ce c

om

pare

d to

'agein

g o

nly

' scenario

Ageing only

Smoking drops 2.5%

every 5 years

Smoking drops 5% every

5 years

Smoking drops 10% every

5 years

17

Impact of Obesity

-7%

-6%

-5%

-4%

-3%

-2%

-1%

0%

1%

2%

3%

2006

2011

2016

2021

2026

2031

2036

2041

2046

2051

Per

cent diff

ern

ce c

om

pare

d to

'agein

g o

nly

' scenario

Ageing only

Obesity rises 2.5% every

5 years

Obesity drops 5% every 5

years

Obesity drops 10% every

5 years

18

Impact of Promoting Physical Activity

-20.0%

-15.0%

-10.0%

-5.0%

0.0%

5.0%

10.0%2006

2011

2016

2021

2026

2031

2036

2041

2046

2051

Per

cent diff

ern

ce c

om

pare

d to

'agein

g o

nly

' scenario

Ageing only

Physical inactivity rises

2.5% every 5 years

Physical inactivity drops

5% every 5 years

Physical inactivity drops

10% every 5 years

19

Impact of Midlife Obesity on Dementia Prevalence

• Risk of dementia 1.64x for midlife obesity and 1.26x for midlife overweight versus midlife normal weight (Low BMI in midlife compared with normal BMI - 1.96 risk of developing AD) (Anstey et al 2011)

• Use dynamic modelling to project future proportions and numbers of older people with a history of a given BMI status at their midlife

• Model impact of midlife BMI on dementia in older population

● Compare ageing only and BMI factored ‘what-if’ projections

Prevalence of Dementia by BMI Status

20

0%

10%

20%

30%

40%

50%

60%

70%

80%

65-69 70-74 75-79 80-84 85-89 90+ 65-69 70-74 75-79 80-84 85-89 90+

Male Female

prev_normal prev_obese prev_overwt prev_underwt prev_total

Estimated Historical and Predicted Prevalence of BMIs at 50 years of age

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Male Female

● ‘Obs’ = estimated historical data.

Male

Female

Male

Female

Percentage of Older Persons who were Obese at Midlife

Projected Prevalence of Dementia with and without factoring midlife BMI profile

In 2050, there will be 14% more people aged 65 years and over living with dementia than that estimated on the basis of demographic ageing only.

Impact of Changing Prevalence of Midlife Obesity

• Persons with Type 2 diabetes exhibited significantly increased risk of all dementia RR = 1.66, and risk of AD was also elevated for men, RR = 2.27 and for women, RR = 1.37 (population based cohort study in Rochester, Minnesota)(Leibson, 1997)

• A meta-analysis found diabetes was associated with a 47% increased risk of any dementia, a 39% increased risk of AD, and a 138% increased risk of VaD (Lu, 2009)

• 2% of cases of AD could be attributed to diabetes (Barnes & Yaffe, 2011)

• Prevention of diabetes could reduce the incidence of mild cognitive impairment and dementia by 5% (Ritchie et al, 2010)

Dementia and Diabetes

Decomposition of the Projected Diabetic Population – Ageing vs Lifestyle Factors

0.0

0.5

1.0

1.5

2.0

2.5

3.0

2007 2052 2052

Base Case

Number of Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

2007 2052 2052

Base Case

Prevalence of Diabetics

Prevalence

0.0

1.0

2.0

3.0

4.0

5.0

6.0

2007 2052 2052

Base Case

Number of Pre-Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

2007 2052 2052

Base Case

Prevalence of Pre-Diabetics

Prevalence

0.0

0.5

1.0

1.5

2.0

2.5

3.0

2007 2052 2052

Ageing Population

Base Case

Number of Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

2007 2052 2052

Ageing Population

Base Case

Prevalence of Diabetics

Prevalence

0.0

1.0

2.0

3.0

4.0

5.0

6.0

2007 2052 2052

Ageing Population

Base Case

Number of Pre-Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

2007 2052 2052

Ageing Population

Base Case

Prevalence of Pre-Diabetics

Prevalence

0.0

0.5

1.0

1.5

2.0

2.5

3.0

2007 2052 2052

Lifestyle Factors

Ageing Population

Base Case

Number of Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

2007 2052 2052

Lifestyle Factors

Ageing Population

Base Case

Prevalence of Diabetics

Prevalence

0.0

1.0

2.0

3.0

4.0

5.0

6.0

2007 2052 2052

Lifestyle Factors

Ageing Population

Base Case

Number of Pre-Diabetics

Millions

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

2007 2052 2052

Lifestyle Factors

Ageing Population

Base Case

Prevalence of Pre-Diabetics

Prevalence

The Comparative Contributors to the Projected Diabetic Population

2007 2052 % of Increase

Pre-Diabetes

Base 2,573.307

Ageing Population 1,592.681 63.61%

Lifestyle Factors 911.215 36.39%

Total 2,573.307 5,077.203

Diabetes

Base 1,186.434

Ageing Population 1,061.649 60.34%

Lifestyle Factors 697.767 39.66%

Total 1,186.434 2,945.851

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Conclusions

• Despite the significant health and cost burden associated with dementia, there is a major gap in our knowledge about future impacts and the role prevention strategies might play in reducing these.

• Need to better understand the role and impact of modifiable risk factors

• Dementia (and Diabetes) simulation models provide an new and different evidence base for informing health policy.

• K. J. Anstey, N. Cherbuin, M. Budge and J. Young (2011) Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. obesity reviews (2011) 12, e426–e437, doi: 10.1111/j.1467-789X.2010.00825.x

• Barnes DE, Yaffe K. (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol, 10(9):819-828.

• Hamer M, Chida Y. (2009) Physical activity and risk of neurodegenerative disease: a systematic review of prospective studies. Psychol Med, 39:3-11.

• C. L Leibson, W. A. Rocca, V. A. Hanson, R. Cha, E. Kokmen, P. C. O'Brien, and P. J. Palumbo (1997) Risk of Dementia among Persons with Diabetes Mellitus: A Population-based Cohort Study American Journal of Epidemiology, Vol. 145, No. 4

• Lu F-P, et al. Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One, 2009, 4(1): e4144. doi:10.1371/journal.pone.0004144.

• Ritchie K, et al. Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors. BMJ, 2010, 341:c3885. doi:10.1136/bmj.c3885

• Rovio S, et al. (2005) Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol, 4:705-711.

• Sofi F, et al. (2011) Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med, 269:107-117.

• Farrow, M & O’Connor, E (2012). Targeting Brain, Body and Heart For Cognitive Health and Dementia Prevention-Current Evidence and Future Directions, Paper 29, Alzheimer’s Australia.

References