Med in Small Doses - Alzhiemer's Disease


This is part of the Med in Small Doses series, which aims to give you a snapshot of a disease or disorder.  

Most common dementia.    F>M.      65% of dementia at all ages (K&C).     Prevalence doubles every 5 years after age 65.     5-10% familial.     Insidious onset.

PATHO: ↓ cholinergic neurons in hippocampus & prefrontal cortex. Amyloid angiopathy. Widened Sulci. Hydrocephalus ex vacuo Medial temporal lobe atrophy.
The cognitive changes in AD follows a characteristic pattern, beginning with memory impairment and progressing to language (naming, comprehension and finally fluency) and visuo-spatial deficits.
Cortical atrophy with neuritic plaques (Aβ) and neurofibrillary tangles (tau). Cleavage by α & γ = normal. Β-secretase + γ → Aβ formation → neurotoxic.

Two Types:
Early Onset (<60yo & linked to genetics); Late Onset (>60yo & more common)

Dx Criteria: Dx of AD is made by clinical assessment. Memory impairment & ≥1 of; Aphasia, Apraxia, Agnosia, ↓ executive function. Ø Delirium or other CNS disturbance.

FEATURES
RONALD (Ronald Reagan, a famous victim):
R eduction of Ach
O ld age
N eurofibrillary tangles
A trophy of cerebral cortex (diffuse)
L anguage impairment
D ementia (MC in elderly)/ Down's syndrome

COMMON CHARACTERISTICS
ALZHEIMER'S:
A nterograde amnesia is usually first sign
L ife expectancy increase shows more cases in recent years
Z apped (loss of) acetylcholinergic neurons
H ereditary disease
E ntire hippocampus becomes affected
I dentified by neurofibrillary tangles
M utation in amyloid genes associated w/ disease
E ntorhinal areas degenerate first
R etrograde amnesia ultimaltely develops
S enile plaques are formed at synapse

RFs:
  1. Advancing age
  2. FHx
  3. ApoE-ε4 genotype
  4. Obesity
  5. Insulin resistance
  6. ↑Lipids
  7. HTN
  8. Inflammatory markers
  9. Down syndrome
Ix: MMSE, MRI, Screen for hypothyroidism & B12 deficiency 

Tx: AChE inhibitors (donepezil, rivastigmine, galantamine). NMDA blocker (Memantine)  to decrease glutamate excitation. Ginkgo biloba, Antioxidants (Vit E), Psychosocial interventions.

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