W7L2 - AD Flashcards
Diagnosis of Alzheimer’s Disease
Definitive diagnosis of AD: Only be made on PATHOLOGY
Can only diagnose Dementia of the Alzheimer Type (DAT) i.e. symptoms of Alzheimers
Aetiology of AD. When does it rise.
- Majority arise sporadically. Age major risk factor
- Rare early onset autosomal dominant cases:
Mutations in 3 genes: 1.) amyloid precursor protein (APP) 2.) presinilin 1 (PSEN1) 3.) presenilin 2 (PSEN2) >>> Alters production of amyloid β (Aβ) peptide (principal component of senile plaques)
Aetiology for AD. What are the factors? Who are more prone?
- Down syndrome (occurs earlier 40s)
- No precipitating/cause factors known (only head injury has some evidence)
- Can have sudden decompensation
Clinical Features of DAT: Onset and Course
Onset:
Insidious (1-2 years)
Course:
Slow deterioration over years. Occasional plateaus in deterioration (M = 8.5 to death)
Clinical Features of DAT: Phases
Phase 1: 2-3 years
Phase 2: Rapid deterioration
Phase 3: Terminal Stage
Clinical Features of DAT: Phase 1
Failing memory (amnestic presentation)
Muddled inefficiency in daily activites
Spatial disorientation
Mood disturbance can occur (agitated or
apathetic)
Clinical Features of DAT: Phase 2
Intellect and personality deteriorate
Focal symptoms appear (dysphasia, dyspraxia,
agnosia and acalculia)
Disturbance of posture and gait, increased
muscle tone
Delusions/hallucinations can occur
Clinical Features of DAT: Phase 3
Profound apathy, become bed ridden
Eventually lose neurological function
Bodily wasting occurs
Probable AD
Deficits in 2 or more areas of cognition
– Amnestic presentation: most common
– Nonamnestic presentations: Language, Visuospatial
Executive dysfunction
- Progressive worsening of memory and/or other
cog. functions - No disturbance of consciousness
- Onset between 40 and 90
- In the absence of other causes
- Biomarkers
Possible AD
- Made on the basis of dementia syndrome if
have VARIATIONS IN ON SET/PRESENTATION
OR
- Made in the presence of another disorder, which is not considered to be the cause of the dementia
Definite AD
Histopathological evidence of AD obtained
from biopsy or autopsy
What is the patholoy of AD
1) Grossly atrophied brain
- Affects frontal and temporal lobes > parietooccipital
regions
2) Extensive degeneration of neurons + gilal cell proliferation
3) Extensive senile plaques and neurofibrillary tangles
Intensity of neuropathological features correlates closely with severity of dementia
Course of neuropathological changes
1) Commence in hippocampus/MTL
2) Spread posteriorly to parietal cortex
3) Spreads to involve frontal cortex
Clinical pattern of cognitive impairment in
DAT – Amnesia. What happens when MTL impairs
– Anterograde memory:
• Impaired new learning
• Impaired delayed recall
• Poor recognition memory
– Retrograde memory:
• Intact for remote memories
• Reduced for recent retrograde memories
Clinical pattern of cognitive impairment in
DAT – Amnesia. What happens when spread posteriorly to parietal cortex
1) Wernicke-type (Word salad. Fluent content-less) aphasia
2) Visuospatial deficits and topographical
disorientation
– Dyspraxia, Agnosia, Dyscalculia
