3 Clinical psychopharmacology3.3 Pharmacodynamics
3.3.2.5 Medicines for dementia and neurodegeneration
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Written by Resident Doctor Committee · Published
New in the 2027 syllabus
The College added this topic for exams from January 2027.
Symptomatic treatment
These medicines can improve symptoms. They do not restore neurones that have already been lost.
Cholinesterase inhibitors slow the breakdown of acetylcholine, so more of it is available to nerve cells.
Memantine limits excessive activity at N-methyl-D-aspartate (NMDA) receptors. It is used in moderate to severe Alzheimer's disease.
Medicine | Mechanism | Adverse effects or monitoring |
|---|---|---|
Donepezil | Reversibly inhibits acetylcholinesterase | Nausea, diarrhoea, bradycardia and syncope |
Galantamine | Inhibits acetylcholinesterase | Gastrointestinal effects; concerns about cardiac conduction |
Rivastigmine | Inhibits acetylcholinesterase and butyrylcholinesterase (a second enzyme that breaks down acetylcholine) | Gastrointestinal effects; skin reactions with patches |
Memantine | Uncompetitive NMDA receptor antagonist | Dizziness and constipation; review the dose in renal impairment |
The type of dementia matters. A treatment that suits Alzheimer's disease is not automatically suitable for frontotemporal dementia or purely vascular dementia.
Check the anticholinergic burden. Anticholinergic drugs can worsen cognition and work against cholinergic treatment. Review the medication list whenever you consider a cognitive enhancer.
Anti-amyloid immunotherapy
Lecanemab and donanemab are monoclonal antibodies directed against amyloid. In selected patients with early Alzheimer's disease they can slow decline.
Slower decline is not recovery. Patients may keep deteriorating even when the treatment gives a relative benefit.
Who can be treated
The patient must be at a compatible early clinical stage.
Amyloid pathology must be confirmed.
A specialist must assess the risks of treatment.
UK licences restrict treatment to people who carry no apolipoprotein E4 allele or only one copy (heterozygotes). People with two copies (homozygotes) have a less favourable balance between benefit and the risk of imaging abnormalities.
Regulatory authorisation and an NHS funding recommendation are separate decisions. Check whether treatment is actually available under current local arrangements.
Amyloid-related imaging abnormalities
These are changes on brain scans caused by anti-amyloid treatment, known as ARIA.
Abnormality | What it means | Assessment |
|---|---|---|
ARIA-E | Vasogenic oedema (fluid leaking into brain tissue) or sulcal effusion | Fluid-sensitive magnetic resonance sequences |
ARIA-H | Microhaemorrhages or superficial siderosis | Blood-sensitive magnetic resonance sequences |
Scheduled magnetic resonance imaging (MRI) can pick up abnormalities before symptoms appear.
During treatment, new headache, confusion, visual symptoms or focal neurological signs need prompt assessment. Do not assume they are just dementia progressing.
Under the UK licences, anticoagulant treatment and pre-existing cerebral amyloid angiopathy are contraindications. Previous haemorrhage and other imaging exclusions also need specialist review.
Other neurodegenerative presentations
Parkinson's disease dementia may be treated with a cholinesterase inhibitor. Rivastigmine has an established role.
Dopamine-enhancing treatments may improve movement but worsen hallucinations or impulse control. Weigh the neurological and psychiatric effects together.
Agitation or psychosis: look first for pain, delirium, distress caused by the environment and adverse drug effects. Only then consider adding a sedative or antipsychotic.