Aging vs AD

1. Aging vs AD • Memory changes not disabling/severe • No effect on long-term memory • Non-memory cognitive domains unaffected • Progression less apparent

2. Why Early Diagnosis of AD is Important • Identify sources of excess disability • Differential diagnosis • Pharmacologic/non-pharmacologic interventions • Adjustment and planning for the family • Greater competency for decision-making • Address patient safety and vulnerability

3. Scope of the Problem • Annual cost to US -- $100 billion • Currently affects 4 million Americans • Number will double in 20 years

5. Estimated Prevalence of AD in America US Census Bureau, 1996; Evans, D. et al. (1990)

6. Practical Definition of Dementia "A primary and progressive decline of intellect and/or comportment due to a structural brain disease to the point that customary social, professional, and recreational activities of daily living become compromised."

7. DSM-IV CRITERIA FOR ALZHEIMER’S TYPE DEMENTIA • Development of multiple cognitive deficits manifested by both: • Memory impairment • One (or more) of the following cognitive disturbances: • Aphasia • Apraxia • Agnosia • Disturbance in executive functioning

8. DSM-IV CRITERIA FOR ALZHEIMER’S TYPE DEMENTIA • The cognitive deficits in Criteria A1 and A2 each significant impairment in social or occupational functioning and represent a decline from a previous level of functioning. • The course is characterized by gradual onset and continuingcognitive decline. • The cognitive deficits in Criteria A1 and A2 are not due to any of the following: • Other CNS conditions (CVA, PD, HD, subdural hematoma, NPH, brain tumor). • Systemic conditions (hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV) • The deficits do not occur exclusively during the course of a delirium • The disturbance is not better accounted for by a major psychiatric disorder (e.g., depression, schizophrenia).

9. Useful Classification of Dementias • Reversible vs Irreversible • Reversible: B12 deficiency • Irreversible: Alzheimer's disease • Cortical vs subcortical vs mixed • Cortical: Alzheimer's Disease • Subcortical: PD, HD, HIV-Dementia • Mixed: Dementia with Lewy bodies

10. Alzheimer's disease Pick's disease Huntington's disease Progressive supranuclear pals, Parkinson's disease (not all cases) Cerebellar degenerations Amyotrophic lateral sclerosis (ALS) Parkinson-ALS-dementia complex of Guam Hallervorden- Spatz Wilson's Disease Cortical micro-infarcts Lacunar dementia (larger infarcts) Binswanger diseas Cerebral embolic disease Cardiac arrest Cardiac failure (severe) Carbon monoxide Dementia pugilistica (boxer's dementia) Head Injuries AIDS Opportunistic infections Creutzfeldt-Jakob disease Progressive multifocal leukoencephalopathy Post-encephalitic dementia Herpes encephalitis Meningitis or encephalitis Brain abscess Neurosyphilis (general paresis) Normal pressure hydrocephalus Chronic or acute subdural hematoma Primary brain tumor Metastatic tumors (carcinoma, leukemia, lymphoma, sarcoma) Multiple sclerosis Lupus erythematosis Vasculitis Alcoholic dementia Metallic dementia (e.g., lead, mercury, arsenic, manganese) Organic poisons (e.g., solvents, some insecticides) Epilepsy (some cases) Whipple disease (some cases) Heat stroke Hyperthyroid Hypothyriod Hypernatremia Hyponatremia Respiratory diseases Kidney diseases Vitamin Deficiencies (B12, folate) Some Disorders Causing Dementia

11. Causes of Degenerative Cortical Dementias • Alzheimer's Disease • Downs Syndrome assoc. • Dementia with Lewy bodies • Pick's Disease/Fronto-temporal dementia • Focal atrophy w/out distinctive histology

12. Who am I Gradual onset Months – years Progressive course Impaired orientation Memory impairment Poor abstract thought Sleep – multiple awakenings Speech impairment Spatial impairment My memory is bad Tends to be acute Weeks – years Fluctuating course Orientation normal Memory nl (tested carefully) Intact abstract thought Sleep – early, middle, late, hypersomnia Complaints of word finding Normal spatial function Distinguishing Among Dementia and DepressionDementiaDepression

13. Alzheimer's Disease • Most common form of dementia accounting for up to 70% of irreversible cases in the elderly • Currently estimated to affect 4 million individuals • 22,000 people die from Alzheimer's every year • Age related increase in incidence with up to 40% of elderly aged 85 or older meeting diagnostic criteria • Average life expectancy after diagnosis is 8 years and individuals may live up to 20 years

14. Clinical Hallmarks: The 4 A's • Amnesia (loss of memory initially for recent events and ultimately for remote events) • Agnosia (total or partial loss of the perceptive faculty by which persons and things are recognized). For example, a person may not associate a key with its purpose or may be unable to recognize words or to decipher prosody (a form of nonverbal communication) of speech. • Apraxia (inability to carry out a motor function in the absence of any motor weakness, such as having muscle power but being unable to dress oneself) • Aphasia (may include naming difficulties of familiar objects such as parts of clothing).

15. Causes of Alzheimer's Disease • Not known • AD is associated with loss of neurons that produce acetylcholine • AD is associated with deposition of beta amyloid plaques • AD is associated with neurofibrillary tangles

16. Risk Factors • Age- prevalence doubles every 5 years over age 65. • Head trauma • Lower education • Loss of estrogen at menopause • Diabetes • Cerebrovascular disease

17. Genetics of Alzheimer's • Majority of cases are sporadic • Familial AD inherited in autosomal dominant pattern accounts for <10% of cases • For first degree relatives, total lifetime risk increases from 23% to 48%. • Early onset AD associated with mutations on chromosomes 1, 14, 21(APP) • Late onset AD associated with mutations on chromosomes 12(ApoE) and 19.

18. Diagnostic Criteria for Dementia with Lewy Bodies • Dementia may have less prominent memory impairment at onset. Cognitive deficits in attention, frontal-subcortical skills, and visuospatial abilities may be prominent. • Core features • Fluctuation of cognition; pronounced variation n attention and alertness. • Hallucinations: recurring, visual, well-formed and detailed • Spontaneous parkinsonism

19. Other Features of Dementia with Lewy Bodies • Repeated falls • Syncope • Delusions • Sensitivity to neuroleptics

20. Pathological Hallmarks of Dementia with Lewy Bodies • Cortical Lewy bodies • Beta amyloid plaques • Neurofibrillary tangles • Neuronal and synaptic loss

21. Pick's Disease/Fronto-temporal Dementia • aka "Frontal Lobe Dementia" • Heterogenous disorders with similar, but distinguishable behavioral profiles • Disease affects mainly the frontal lobes

22. Clinical Presentation of Frontal Dementias • Both present with a "Frontal syndrome" • Behavioral dyscontrol • Disinhibition or apathy • Neglect of personal hygiene • Compulsions or rituals • Poor planning and judgement • Pick's disease has language impairment, while fronto-temporal dementia does not • Pick's disease has Pick bodies and there may be a genetic component (autosomal dominant)