Alzheimer's Dementia Flashcards
What blood work to do for a presentation consistent with AD?
- CBC
- Lytes
- Calcium
- Glucose
- TSH
- B12
What are the recommendations regarding genetic testing/screening for AD?
Not recommended, PPV and NPV are low
What is the amyloid hypothesis in AD?
Normal conditions = amyloid precursor protein is cleaved by alpha secretase
In AD = APP mutations inc beta secretase and PSEN1/2 inc gamma secretes activity = abnormal cleavage of amyloid precursor protein = excess amyloid accumulation = neuronal toxicity in CNS
What are the 2 biggest risk factors for AD?
- Age
- Family history
What percentage of AD cases are due to familial?
1%
Early AD
Autosomal dominant inheritance
PSEN1/2, APP
What gene is associated with late AD?
APOE4
APOE2 = protective
APOE3 = neutral
What are the DSM-V diagnostic criteria for AD?
A. Evidence of significant cognitive decline in 1+ cognitive domains (executive function, language, social cognition, attention, learning and memory, perceptual motor)
B. Deficits interfere with ADLs (assist with IADLs)
C. Not exclusively in context of delirium
D. Not better explained by another mental disorder
E. Insidious onset and gradual progression in at least 2 domains
F. Either of the following:
1. AD mutation
2. All 3 of: evidence of decline in mem/learning plus another domain, steadily progressive gradual decline no extended plateaus, no evidence mixed etiology
List three proteins found in neurofibrillary tangles
Hyperphosphorylated tau
Ubiquitin
Amyloid beta
Name 6 Alzheimer’s biomarkers being investigated/used in research
- CSF amyloid beta 42
- Amyloid PET
- CSF phosphorylated tau
- Tau PET
- Anatomic MRI
- FDG PET
- CSF total tau
What are 5 characteristics of a good biomarker for the dx of AD?
- High Sn and Sp
- Inexpensive
- Noninvasive
- Reflects physiologic aging process
- React upon pharmacologic intervention
What is the risk of developing AD in a first degree relative of patient?
2-4x increased risk
What is the evidence for donepezil?
- Over 6 months
- Better outcomes for cognition: ADAS-Cog, MMSE, Severe impairment battery
- Better outcomes for function: ADL
- Improved global impression
- No QOL changes
10 mg vs 5 mg
- Slightly worse on ADAS-Cog
- Slightly better QOL, fewer AEs and withdrawals
What is the evidence for galantamine?
Dose>8 mg
ER 16-24 mg just as good as BID
Improved
Cognition - ADAS-Cog
Global rating scale
ADCS-ADL, DAD
What is the evidence for rivastigmine?
Improved
Cognition - ADAS-Cog, MMSE
Function - ADLs
Global impression
No change
Behavioural
Caregiver burden
What is the evidence for memantine?
Only in mod-severe AD
Improved
- Global rating
- Cognitive function severe impairment battery
- ADL
- Behaviour and mood
