Cognitive symptoms

Beneficial

• Donepezil

• Galantamine

Likely to be beneficial

• Ginkgo biloba

• Oestrogen (in women)

• Reality orientation

• Selegiline

Trade off between benefits and harms

• Physostigmine

• Rivastigmine

Unknown effectiveness

• Lecithin

• Music therapy

• Nicotine

• Non-steroidal anti-inflammatory drugs

• Reminiscence therapy

• Tacrine

• Vitamin E

Key messages Donepezil

One systematic review and two subsequent RCTs have found that donepezil compared with placebo improves cognitive function and global clinical state at up to 52 weeks in people with mild to moderate Alzheimer’s disease. The review found no significant difference in patient rated quality of life at 12 or 24 weeks between donepezil and placebo. One RCT in people with mild to moderate Alzheimer’s disease found no significant difference in cognitive function at 12 weeks between donepezil and rivastigmine, although significantly fewer people taking donepezil withdrew from the trial for any cause.

Galantamine

RCTs identified by a systematic review, and one additional RCT, have found that galantamine improves cognitive function compared with placebo in people with Alzheimer’s disease or vascular dementia.

Ginkgo biloba

RCTs found limited evidence that ginkgo biloba improved cognitive function compared with placebo in people with Alzheimer’s disease.

Lecithin

Small, poor RCTs identified by a systematic review provided insufficient evidence to assess lecithin in people with Alzheimer’s disease.

Music therapy

Poor studies identified by a systematic review provided insufficient evidence to assess music therapy.

Nicotine

One systematic review found no RCTs of adequate quality on the effects of nicotine.

Non-steroidal anti-inflammatory drugs

One RCT in people with Alzheimer’s disease found no significant difference in cognitive function after 25 weeks treatment with diclofenac plus misoprostol compared with placebo. Another RCT in people with Alzheimer’s disease found that indometacin improved cognitive function after 6 month treatment compared with placebo.

Oestrogen (in women)

One systematic review has found that, in women with mild to moderate Alzheimer’s disease, oestrogen improves cognition over 7–12 months treatment compared with no oestrogen.

Physostigmine

One systematic review in people with Alzheimer’s disease found limited evidence that slow release physostigmine improved cognitive function compared with placebo, but adverse effects, including nausea, vomiting, diarrhoea, dizziness, and stomach pain, were common.

Reality orientation

One systematic review of small RCTs found that reality orientation improved cognitive function compared with no treatment in people with various types of dementia.

Reminiscence therapy

One systematic review provided insufficient evidence to assess reminiscence therapy.

Rivastigmine

One systematic review and one additional RCT have found that rivastigmine improves cognitive function compared with placebo in people with Alzheimer’s disease or Lewy body dementia, but adverse effects such as nausea, vomiting, and anorexia are common. Subgroup analysis from one RCT in people with Alzheimer’s disease suggests that people with vascular risk factors may respond better to rivastigmine than those without. One RCT in people with mild to moderate Alzheimer’s disease found no significant difference in cognitive function at 12 weeks between donepezil and rivastigmine, although rivastigmine significantly increased the proportion of people who withdrew from the trial for any cause.

Selegiline

One systematic review has found that, in people with mild to moderate Alzheimer’s disease, selegiline improves cognitive function, behavioural disturbance, and mood compared with placebo, but has found no significant difference in global clinical state.

Tacrine

Systematic reviews found limited evidence that tacrine improved cognitive function and global state in Alzheimer’s disease compared with placebo, but adverse effects, including nausea and vomiting, diarrhoea, anorexia, and abdominal pain, were common.

Vitamin E

One RCT in people with moderate to severe Alzheimer’s disease found no significant difference in cognitive function after 2 years treatment with vitamin E compared with placebo. However, it found that vitamin E reduced mortality, institutionalisation, loss of ability to perform activities of daily living, and the proportion of people who developed severe dementia.

Behavioural and psychological symptoms

Likely to be beneficial

• Carbamazepine

• Olanzapine

• Reality orientation

• Risperidone

Unknown effectiveness

• Cholinesterase inhibitors

• Haloperidol

• Sodium valproate

• Trazodone

Key messagesCarbamazepine

One RCT found that carbamazepine reduced agitation and aggression compared with placebo in people with various types of dementia.

Cholinesterase inhibitors

One RCT in people with mild to moderate Alzheimer’s disease found no significant difference in psychiatric symptoms at 3 months between galantamine and placebo, but another RCT found that galantamine significantly improved psychiatric symptoms at 6 months compared with placebo. One RCT in people with moderate to severe Alzheimer’s disease found that donepezil significantly improved functional and behavioural symptoms at 24 weeks compared with placebo, but another RCT in people with mild to moderate Alzheimer’s disease found no significant difference in psychiatric symptoms at 24 weeks between donepezil and placebo.

Haloperidol

One systematic review in people with various types of dementia found no significant difference in agitation between haloperidol and placebo, but found limited evidence that haloperidol may reduce aggression.

Olanzapine

One RCT in people with Alzheimer’s disease found that olanzapine (5–10 mg daily) reduced agitation, hallucinations, and delusions compared with placebo.

Reality orientation

One systematic review of small RCTs found that reality orientation significantly improved behaviour compared with no treatment in people with various types of dementia.

Risperidone

One RCT in people with moderate to severe dementia, including Alzheimer’s disease and vascular dementia, found that risperidone significantly improved behavioural and psychological symptoms over 12 weeks compared with placebo, but another RCT in people with severe dementia and agitation found no significant difference in symptoms over 13 weeks.

Sodium valproate

One RCT found that sodium valproate reduced agitation over 6 weeks in people with dementia, but another RCT found no significant difference in aggressive behaviour over 8 weeks between sodium valproate and placebo.

Trazodone

One RCT in people with Alzheimer’s disease found no significant difference between trazodone and haloperidol in reducing agitation. Another RCT in people with dementia plus agitated behaviour found no significant difference in agitation among trazodone, haloperidol, behavioural management techniques, and placebo. The RCTs may have been too small to exclude a clinically important difference.