Alzheimer's disease Flashcards
Dementia statistics
1/11 Canadians over 65 affected by dementia
Estimated lifetime risk: 10-12%
Clinical features of Alzheimer’s disease
insidious onset slowly progressive memory loss aphasia, apraxia changes in judgment/reasoning spatial disorientation, behavioural changes
Disease duration of Alzheimer’s disease
variable
avg time between diagnosis and death: 8-9 years
Age of onset of AD
Early =65
Dementia causes
AD (66%) Vascular (10-20) LBD (10-20) Frontotemporal dementia (5-15) Others: infection, diabetes, thyroid, vitamin deficiency, etc
Pathology of Alzheimer’s disease
Accumulation of beta amyloid plaques neurofibrillary tangles of Tau protein Loss of cerebral cortex volume due to cell death Senile plaques Gliosis
Diagnosis of Alzheimer’s disease
typically a diagnosis of exclusion clinical diagnosis ~90% correct Neuropathological diagnosis certain (suspicion until then) may involve: - neurological examination - CT/MRI - SPECT - blood work - neuropsychological, neuropsychiatric evaluation - functional assessment - family history
AD genetics
Most are sporadic: 75-95% Multifactorial susceptibility genes enviornmental factors aging is greatest risk factors affected first degree relative: 15-30% recurrence risk 15-30 to
Sporatic AD genetics
ApoE gene one of 40+ susceptibility genes identified, shows strongest effect exact role unclear 3 alleles: APOE2, 3, 4 APOE4 greatest risk for sporadic AD - heterozygote: 3x popn risk - homozygote: 8x pon risk clinical genetic testing not recommended NOT causative!
Environmental factors implicated in sporadic AD
mental stimulation head injury mood disorders/stress vitamins/herbal remedies? vascular health - exercise, diet, hypertension, high cholesterol, diabetes
Familial AD
rare, 5-25% of all cases
Clinically indistinguishable from sporadic
Can be early or late onset
Hallmarks:
- multiple family members with AD
- affected parents having affected children over many generations
- multiple siblings affected
- similar age of symptom onset within family
Familial AD genetics
autosomal dominant
almost complete penetrance (50% recurrent risk in first degree relatives)
3 causative genes identified:
- Presenilin 1, 2, amyloid precursor protein
Affect processing of APP and increase in beta amyloid peptide
Only for early-onset
No genes identified for late-onset familial AD yet
Genetic testing for familial AD
UT - strict inclusion criteria, no cost, 12 mo turnaround time
Clinical testing from US, 2500$, 2-4 wks
relevant ONLY if early-onset familial AD
negative: does not R/O possibility
AD gross pathology
general brain atrophy cerebral hemispheres more involved cerebellum spared Hydrocephalus due to increase in size of ventricles cerebral cortical atrophy
AD distribution of pathology
predominantly in association cortices
no blindness/numbness in AD
loss of planning
loss of hippocampus: mood, personality, emmory