Download - Research on Young-Onset Dementia and Its Implications for Criminal and Civil Forensic Cases
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AAPL 2009
Young-Onset Dementias
Forensic Implications
Presented by: Ryan C.W. Hall, M.D. and Brian S. Appleby, M.D.
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Disclosures
• Co-Investigator of a multi-center trial of memantine for the treatment of frontotemporal dementia (Forest Laboratories)
• Honoraria from the CJD Foundation
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Objectives
I. Demonstrate the differential diagnosis for young-onset dementias
II. Describe the neuropsychiatric complications of young-onset dementias
III. Understand the management and legal complications of young-onset dementias
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Dementia
1. Cognitive impairment
2. Intact consciousness
3. Functional impairment
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CognitionShort-term memory
Language
Praxis
Visuospatial skills
Executive Functioning
Emotion and personality
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Definition
Cognitive and functional impairment in individuals <65 years of age
Further classification:
Early-onset: <65 years of age
Young-onset: <45 years of age
Kelley BJ, et al. Arch Neurol, 2008
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Cognitive Symptoms
Memory Clinic, <60 years of age:
-55%, no cognitive deficits
-13%, mild cognitive complaints
-17%, selective cognitive deficits
-15%, demented
Vraamark Elberling T, et al. Neurology, 2002
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No Cognitive Deficits
Vraamark Elberling T, et al. Neurology, 2002
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Epidemiology (45-64 years of age)
Incidence: 11.5 per 100,000 individuals
Prevalence: 98.1 per 100,000 individuals
Mercy L, et al. Neurology, 2009Harvey RJ, et al. J Neurol Neurosurg Psychiatry 2003
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Epidemiology
Age Range Prevalence rate (per 100,000)
Male Female Total
30-64 62.6 45.5 54.0
45-64 119.8 76.5 98.1
Harvey RJ, et al. J Neurosurg Neurol Psychiatry, 2003
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April 12, 2023 11
Causes of young-onset dementia
Alzheimer diseaseCerebrovascular diseaseFrontotemporal dementiasMetabolic disordersTraumatic brain injuryHIV/AIDS dementia
Alcohol-related dementiaHuntington diseasePrion dementiasMultiple sclerosisAutoimmune illnesses
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Fujihara S, et al. Arq Neuropsiquiatr, 2004
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Papageorgiou SG, et al., Alzheimer Dis Assoc Disord, 2009
AD
FTD
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<45 years of age
Kelley BJ, et al. Arch Neurol, 2008
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Challenges
• Diagnosis• Occupational • Financial• Social• Family-spouse and children• Behavioral issues• Better overall health and mobility• Disease specific-FTD, fAD, CJD
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ZBI=Zarit Burden Interview Johns Hopkins FTD/YOD Clinic
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17Delany N, et al. Int J Ger Psych, 1995Sperlinger D, et al. Int J Ger Psych, 1994
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Appleby BS, et al. [In Press]
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Velakoulis D, et al. BJP 2009
The solid curve shows the percentage of patients with frontotemporal dementia presenting with schizophrenia-like psychosis; the dashed curve shows the cumulative number of
patients with frontotemporal dementia
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Appleby BS, et al. J Neuropsychiatry Clin Neurosci, 2007
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Delayed Presentation
From onset to initial evaluation3 years (Fujihara S, et al. Arq Neuropsiquiatr, 2004)
3 years (Papageorgiou SG, et al. Alzheimer Dis Assoc Disord, 2009)
2 years (Kelley BJ, et al. Dement Geriatr Cogn Disord, 2009)
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Appleby, B. S. et al. Arch Neurol 2009;66:208-215.
Creutzfeldt-Jakob disease(Log-rank test, χ2= 18.35, P = 0.003)
Mean age=59.7
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Referral Patterns
Newens AJ, et al. Br J Gen Pract, 1994
Neurologist-> 63%
Psychiatrist-> 27%
Other physician->9%
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Work-up Patterns
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Why Psychiatrists?
• High prevalence of behavioral disorders
• Frequently taking psychotropic meds
– 41% on neuroleptics
• High degree of strain and psychiatric morbidity in caregivers
• Need for education
Baldwin RC. Psychiatr Bull, 1994Kelley BJ, et al. Dement Geriatr Cogn Disord, 2009
Delany N & Rosenvinge H. Int J Ger Psychiatry, 1995
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We are already seeing them!
Newens AJ, et al. Br J Gen Pract, 1994
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DiagnosisHistory
• Course of illness
• Pattern of cognitive deficit
• Family history
• Other neurological signs/symptoms
• Other systemic illness
• Social/Drug history
Ridha B & Josephs KA. The Neurologist, 2006
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Preliminary work-up
• CBC• Coagulation studies• CMP• TFT’s• Vitamin B12 & folate• Fasting lipid panel• RPR• ESR & CRP
• Urine toxicology• Brain MRI• Neuropsych testing
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Expanded work-up
• Antibody screen• Ceruloplasmin• Iron studies• Heavy metal screen• SPEP/UPEP• Homocysteine• NH4• Genetic testing
• Brain PET scan• EEG• LP• Whole body PET
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Alzheimer’s disease (AD)
• Most prevalent dementia
• Presents differently in younger patients– Posterior cortical atrophy– Driving concerns
• Familial illness (<1%)– Pre-senilin-1&2– Amyloid precursor protein
Tang-Wai DF, et al. Neurology, 2004
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Case• 57-year-old man with AD
• Initial symptoms were visuospatial impairment and acalculia
• Police contact for suspicions of driving while intoxicated
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Frontotemporal Lobar Degeneration
Frontotemporal Dementia
Progressive Non-fluent
Aphasia
SemanticDementia
Neary D, et al. Neurology, 1998
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FTD Core Diagnostic Features
A. Insidious onset, gradual progression
B. Early decline in social interpersonal conduct
C. Early impairment in regulation of personal conduct
D. Early emotional blunting
E. Early loss of insight
Neary D, et al. Neurology, 1998
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FTDSupportive diagnostic features
A. Behavioral disorder
B. Speech and language disorder
C. Physical symptoms
D. Investigational findings1. Neuropsychological testing
2. EEG
3. Brain imaging
Neary D, et al. Neurology, 1998
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@Primitive reflexes and drives
Rational thought, inhibition
Illustration from Wider Than The Sky: The Phenomenal Gift Of Consciousness by Gerald Edelman
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Phineas Gage
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Case
• 55-year-old gentleman with FTD• First presentation at airplane security• Multiple family stressors
– Social– Occupational– Financial
• Spouse displays positive coping skills in advocacy
• Solution: Travel letters
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Case
• 59-year-old women with cortical basal degeneration
• Expressive aphasia and acalculia
• Hands blank checks to clerks
• Young children, ages 9 and 14
• Solution: Pre-paid credit/debit cards and online video communication
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Traumatic Brain Injury
• Cognitive and neuropsychiatric effects
• Coup/contre-coup preferentially affect frontal lobe nerve fibers
• Often associated with alcohol use
• Chicken/Egg scenario
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N
Appleby BS, et al. Dement Geriatr Cogn Disord, 2008
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Creutzfeldt-Jakob disease
• Prion disease
• Rapidly progressive dementia
• Symptoms– Dementia– Cerebellar impairment– Vision impairment– Pyramidal/Extrapyramidal symptoms
• Mean age of onset=62
• Mean survival time=4-6 months
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Creutzfeldt-Jakob disease(CJD)
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Definite CJD
Histology Immunohistochemistry
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Probable CJD
I. Two symptoms:A. Cerebellar and/or visual impairment
B. Myoclonus
C. Akinetic mutism
D. Pyramidal and/or Extrapyramidal symptoms
II. Diagnostic InvestigationsA. Electroencephalogram (EEG)
B. Cerebrospinal 14-3-3 protein
C. Brain MRI
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EEGPeriod sharp wave complexes
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Brain MRIDWI/FLAIR
Cortical ribbon
Basal ganglia
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Case #4
• 57-year-old man with sCJD
• Social stressors– Lack of support– Curiosity– Social construction (e.g. mad-cow disease)
• Solution: Family gives vague explanation (e.g. neurodegenerative illness)
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King S. Lancet, 2008
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Huntington’s disease
• Trinucleotide repeat (CAG) disorder
• Genetic anticipation
• Atrophy of the caudate nucleus
• Movement (e.g. chorea), cognitive, and psychiatric symptoms
• Increased risk of suicide
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Case
40-year-old male with moderate dementia and psychosis from HD attacks a medical student during an examination.
•Risk assessment
•Consent for treatment
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CASE PRESENTATIONS
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Case #1
• 64 y.o. Caucasian female
• Problems remembering dates and conversations, would repeat self
• Gradual progression with some daily fluctuations
• ↑ irritability, ↑ fatigue, ↓ functioning
• Social withdrawal, suspicious at times
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Brain MRI
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Case #2
• 51 y.o. Caucasian male
• Trouble focusing, prioritizing, organizing
• Increase frequency and severity of angry outbursts
• Loss of empathy
• Rigid and resistant to change
• Mini-mental state exam=30/30
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Brain MRI
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Case #3
• 39 y.o. Jordanian male
• Painful paresthesias of his feet (Aug)
• Depression (Sept)
• Forgetful (Nov)
• Inability to dress self (Jan)
• Worsening gait, incontinence, myoclonus (Feb)
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Brain MRI
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Case #4
• 41 y.o. Caucasian female• Following birth of child in her 30’s
became anergic, depressed, and distractable
• Progressed to impulsivity and more distractability (12 car accidents/5 yrs)
• Periods of exhilaration and irritability with poor sleep
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Head CT
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Case #5
• 43 y.o. Caucasian male
• History of alcohol, benzo, opioid abuse
• Found in respiratory distress, obtunded with pinpoint pupils
• Developed depression, apathy, disinhibition, MMSE=20/30
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MRI , 8 months after inhalation
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MRI , 16 months after acute phase
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Thank you
Johns Hopkins FTD/YOD Clinic:
Chiadi Onyike
Mary Anne Wylie
Rebecca Rye
Kate Hicks
Peter Rabins
Kostas Lyketsos