Alzheimer's Disease

What it is

A progressive neurodegenerative disease characterised by extracellular amyloid-β plaques, intracellular tau neurofibrillary tangles, synaptic loss, and brain atrophy. Clinical course progresses from amnestic mild cognitive impairment to dementia over years.

Major risk factors

• Age (single biggest).
• APOE-ε4 genotype (3× risk for one copy, ~10–15× for two).
• Vascular risk factors: hypertension, diabetes, smoking, dyslipidaemia.
• Hearing loss (untreated).
• Sleep disorders including untreated obstructive sleep apnoea.
• Traumatic brain injury history.
• Low education / cognitive engagement.
• Social isolation, depression, physical inactivity.

Current treatments

• Anti-amyloid antibodies (lecanemab, donanemab): slow cognitive decline modestly in early disease; ARIA (oedema/microhaemorrhage) is a significant safety concern, especially in APOE-ε4 carriers.
• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine): symptomatic only.
• Memantine: symptomatic in moderate-severe disease.

Prevention (the bigger lever)

The Lancet Commission estimates ~40% of dementia is attributable to modifiable risk factors. The FINGER trial showed a multimodal lifestyle intervention slowed cognitive decline. Acting on cardiovascular risk, hearing loss, exercise, sleep, and education is high-leverage.

Related entries

FINGER trial, APOE, Sleep optimization.