W7L2 - AD

Definitive diagnosis of AD: Only be made on PATHOLOGY Can only diagnose Dementia of the Alzheimer Type (DAT) i.e. symptoms of Alzheimers

• 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)

• Down syndrome (occurs earlier 40s) • No precipitating/cause factors known (only head injury has some evidence) • Can have sudden decompensation

Onset: Insidious (1-2 years) Course: Slow deterioration over years. Occasional plateaus in deterioration (M = 8.5 to death)

Phase 1: 2-3 years Phase 2: Rapid deterioration Phase 3: Terminal Stage

Failing memory (amnestic presentation) Muddled inefficiency in daily activites Spatial disorientation Mood disturbance can occur (agitated or apathetic)

Intellect and personality deteriorate Focal symptoms appear (dysphasia, dyspraxia, agnosia and acalculia) Disturbance of posture and gait, increased muscle tone Delusions/hallucinations can occur

Profound apathy, become bed ridden Eventually lose neurological function Bodily wasting occurs

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

• 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

Histopathological evidence of AD obtained from biopsy or autopsy

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

1) Commence in hippocampus/MTL 2) Spread posteriorly to parietal cortex 3) Spreads to involve frontal cortex

– Anterograde memory: • Impaired new learning • Impaired delayed recall • Poor recognition memory – Retrograde memory: • Intact for remote memories • Reduced for recent retrograde memories

1) Wernicke-type (Word salad. Fluent content-less) aphasia 2) Visuospatial deficits and topographical disorientation – Dyspraxia, Agnosia, Dyscalculia

Apathy (most common) Agitation

Apathy (most common) Agitation

Work by trying to re-balance the action of acetylcholine No clear evidence that anything prevents AD (Diet, Exercise, etc)

Pathological changes are considerably greater in AD Cognitive function in DAT is significantly impaired relative to same aged peers