Drugs for Alzheimer Disease

Drugs for Alzheimer disease modestly improve or stabilise cognition, function and behaviour for months to a few years. They do not cure the disease. Treatment is combined with control of vascular risk factors, withdrawal of anticholinergic drugs, and support for carers.

Classification. Cholinesterase inhibitors (donepezil, rivastigmine, galantamine); NMDA receptor antagonist (memantine); anti-amyloid monoclonal antibodies (lecanemab, donanemab).

• Donepezil 5 mg daily, increased to 10 mg after 4 weeks.
• Rivastigmine oral 1.5 mg twice daily, increased every 2 weeks to 3 to 6 mg twice daily; patch 4.6 mg/24 h, then 9.5 mg/24 h.
• Galantamine prolonged release 8 mg daily, increased every 4 weeks to 16 to 24 mg daily.
• Memantine 5 mg daily, increased weekly to 20 mg daily.
• Lecanemab 10 mg/kg intravenously every 2 weeks; donanemab 700 mg intravenously every 4 weeks for 3 doses, then 1,400 mg every 4 weeks.

Differences. Cholinesterase inhibitors are used in mild to moderate disease and donepezil also in severe disease. Memantine is used in moderate to severe disease. Anti-amyloid drugs apply only to early disease with confirmed amyloid pathology.

• Before treatment: exclude reversible causes: delirium, depression, vitamin B12 and thyroid disorders, syphilis, HIV-associated neurocognitive disorder, alcohol, and drug effects.
• Mild to moderate disease: start a cholinesterase inhibitor; add memantine in moderate to severe disease.
• Behavioural symptoms: non-drug measures first. Antipsychotics (risperidone 0.25 mg twice daily) only for severe distress or risk, for the shortest time, with review within 6 weeks, because they raise mortality and stroke risk.
• Dementia with Lewy bodies and Parkinson disease dementia: rivastigmine; avoid antipsychotics, which can cause severe sensitivity reactions.
• Anti-amyloid antibodies: only with confirmed amyloid, MRI before and during treatment (amyloid-related imaging abnormalities), and APOE testing; cost and MRI needs make them unavailable in most East African settings.

Selection. Reassess cognition and function every 6 months; stop when there is no benefit, intolerance, or end-stage disease.

Contraindications. Class-specific; for example cholinesterase inhibitors in heart block, and anti-amyloid drugs in anticoagulation, bleeding disorders and multiple microhaemorrhages.

Adverse effects. Nausea, vomiting, diarrhoea, anorexia and weight loss, bradycardia and syncope (cholinesterase inhibitors); dizziness, headache and constipation (memantine); amyloid-related brain oedema and haemorrhage (anti-amyloid antibodies).

Interactions. Anticholinergic drugs oppose cholinesterase inhibitors. Beta blockers, digoxin and amiodarone add bradycardia.

Special groups.

• Pregnancy and breastfeeding: not indicated.
• Older adults: baseline pulse and ECG; weigh regularly.
• Kidney impairment: adjust memantine.
• Liver impairment: reduce cholinesterase inhibitor doses.

Monitoring. Pulse, weight, gastrointestinal tolerance, falls, and cognition and function scores.

Referral and escalation. Rapidly progressive decline, early onset under 65, focal signs, seizures or severe behavioural disturbance need specialist review.