Cholinesterase inhibitors explained

What cholinesterase inhibitors are

Cholinesterase inhibitors are medicines that increase the level of acetylcholine, one of the brain's main signalling chemicals, by blocking the enzyme that breaks it down. Acetylcholine is closely involved in attention and memory, and is reduced in Alzheimer's Disease. By raising its level in the brain, these medicines can partially compensate for the loss.

Three cholinesterase inhibitors are licensed in the UK for Alzheimer's Disease:

• Donepezil (often known by its brand name Aricept), as a tablet or orodispersible tablet.
• Galantamine, as a modified-release capsule or oral solution.
• Rivastigmine, as a capsule, oral solution, or transdermal patch.

A fourth medicine, Memantine, is also licensed for moderate to severe Alzheimer's but works through a different mechanism (NMDA-receptor antagonism). It is often combined with a cholinesterase inhibitor when symptoms progress.

Who can be prescribed these medicines in the UK

NICE Technology Appraisal TA217 recommends cholinesterase inhibitors as options for managing mild to moderate Alzheimer's Disease, including the Alzheimer's component of Mixed Alzheimer's and Vascular Dementia. Severity is typically defined by Mini Mental State Examination (MMSE) score: mild Alzheimer's MMSE 21 to 26, moderate MMSE 10 to 20. Some clinicians use ACE-III as an equivalent measure, and the threshold is interpreted in clinical context, not by score alone.

These medicines are not recommended for Mild Cognitive Impairment, for pure Vascular Dementia without an Alzheimer's component, or for Behavioural Variant Frontotemporal Dementia. They can be used in Lewy Body Dementia with appropriate caution.

How much benefit can be expected

About six in ten people who tolerate a cholinesterase inhibitor experience a measurable improvement in attention, memory and the ability to carry on day-to-day activities. The most consistent gains are in alertness, fluency in conversation, and engagement with familiar activities. Benefit is generally modest, typically a four to six month "shift back" in the disease trajectory, but for many people that improvement is meaningful and durable.

What these medicines do not do is cure or stop the underlying disease. Progression continues, but from a slightly better starting point.

Before starting: the work-up

UK practice is to confirm the diagnosis through structured assessment (including a cognitive test such as the ACE-III and a structural scan such as MRI), and to take a baseline Electrocardiogram (ECG). The ECG is used to check for pre-existing bradycardia or heart block, which would make cholinesterase inhibitors unsuitable or require cardiology input.

Other pre-prescribing considerations include current medications (some interactions exist), a history of asthma or peptic ulcer, and any history of seizures.

How treatment is started and titrated

Treatment is usually started at a low dose and increased after about four weeks if it is well tolerated. The example below is illustrative; your prescriber will adjust to your situation:

• Donepezil: 5 mg once daily for four weeks, then 10 mg once daily.
• Galantamine (modified-release): 8 mg once daily for four weeks, then 16 mg, with a possible further increase to 24 mg.
• Rivastigmine patch: 4.6 mg per 24 hours for at least four weeks, then 9.5 mg per 24 hours.

After three months on the target dose, a clinician usually reviews whether the medicine is helping, by comparing the cognitive and functional picture with the pre-treatment baseline.

Side effects

Most side effects are mild and transient. The commonest are:

• Nausea, occasionally vomiting, in the first one to two weeks;
• Loose stools or diarrhoea;
• Reduced appetite and a small amount of weight loss;
• Vivid dreams or sleep disturbance, sometimes helped by taking the dose earlier in the day;
• Mild dizziness and slight slowing of the heart rate;
• Muscle cramps and occasional restless legs.

Rare but important side effects include bradycardia and falls, peptic ulceration (more often with Rivastigmine), and (very rarely) seizures. Anyone experiencing severe symptoms should contact their prescriber or NHS 111.

Practical points families ask about

Switching between cholinesterase inhibitors

If one cholinesterase inhibitor is not tolerated, another may be. Switching from Donepezil to a Rivastigmine patch can sometimes avoid gastrointestinal side effects, since the patch produces steadier blood levels.

Combining with Memantine

For people who progress from mild to moderate-severe Alzheimer's Disease, Memantine may be added or substituted, often in combination.

Stopping the medicine

People often ask "when should I stop?". There is no universal answer. Most clinicians continue treatment as long as there is evidence of benefit and tolerability, even into more advanced stages, and review every six to twelve months. Sudden discontinuation can sometimes produce a measurable step-down in function.

Cost and access

All four medicines are now generic and inexpensive. NHS prescriptions are free for most people aged 60 and over, and for people on income-related benefits. The Dementia Service can initiate treatment privately and write to your GP for ongoing prescription under shared-care arrangements.

What about the new antibody therapies?

Lecanemab and Donanemab are intravenous monoclonal antibodies that remove amyloid plaques from the brain in early Alzheimer's Disease. Both are licensed by regulators in some countries. NICE's most recent appraisals (June 2025) recommended against routine NHS use of both medicines, citing cost-effectiveness and risk-benefit at the population level. The position may change, and dementia.co.uk will update when it does. See our Lecanemab and Donanemab page.