Overview
Definition
A progressive, irreversible neurodegenerative disease that destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks.
Epidemiology
The most common cause of dementia (60-80% of cases). Risk increases exponentially with age > 65.
Etiology & Risk Factors
- Extracellular accumulation of Beta-amyloid plaques
- Intracellular accumulation of hyperphosphorylated Tau protein (Neurofibrillary tangles)
- Loss of cholinergic neurons in the basal nucleus of Meynert
- Genetics: APOE-e4 allele increases risk
Clinical Symptoms
- Early: Short-term memory impairment (anterograde amnesia), getting lost in familiar places
- Middle: Aphasia (language deficits), Apraxia (loss of learned motor skills), Agnosia (inability to recognize objects/faces)
- Late: Loss of basic activities of daily living (ADLs), incontinence, mutism, dysphagia
Clinical Approach
Diagnosis
- Clinical diagnosis (rule out reversible causes of dementia like B12 deficiency, Hypothyroidism, Neurosyphilis, Depression)
- MRI Brain: Generalized cortical atrophy, especially prominent in the hippocampus and medial temporal lobes
- CSF/PET biomarkers (amyloid/tau) are used primarily in research/trials
Management
- Cholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine) for symptomatic benefit in mild-moderate disease
- NMDA receptor antagonist (Memantine) for moderate-severe disease
- Anti-amyloid monoclonal antibodies (Lecanemab) for early disease (controversial, requires careful monitoring for ARIA - amyloid-related imaging abnormalities)
Complications
- Complete dependence on caregivers
- Wandering and getting lost
- Malnutrition and dehydration
- Aspiration pneumonia (often the ultimate cause of death)