Cholinesterase inhibitors should not be recommended for mild cognitive impairment, says Cochrane review


Early diagnosis and effective treatment of dementia will help large numbers of the population remain independent for longer.

Cholinesterase inhibitors are one of the anti-dementia drugs that are used to treat Alzheimer’s disease, and they are often used immediately after diagnosis.

This new systematic review from the Cochrane Dementia and Cognitive Improvement Group, looks at the safety and efficacy of cholinesterase inhibitors in people with mild cognitive impairment. The question here is whether these drugs can help to prevent the development of dementia in this group of patients.

The reviewers searched systematically for double-blind, placebo-controlled randomised trials of any cholinesterase inhibitor in people with mild cognitive impairment. They found 9 studies (including 5,149 patients), but could not pool them all in a single meta-analysis because they were quite different (particularly in terms of length of the study period).

Here’s what they found:

  • Cholinesterase inhibitors had no effect on cognitive test scores
  • There was no strong evidence that cholinesterase inhibitors prevented dementia
  • As you would expect, people taking cholinesterase inhibitors experienced more side effects than the placebo group:
    • Diarrhoea (RR 2.10; 95% CI 1.30 to 3.39)
    • Nausea (RR 2.97; 95% CI 2.57 to 3.42)
    • Vomiting (RR 4.42; 95% CI 3.23 to 6.05)
    • Cardiac problems were no more likely in either group (RR 0.71; 95% CI 0.25 to 2.02)
    • Muscle spasms/leg cramps (RR 7.52; 95% CI 4.34 to 13.02)
    • Headache (RR 1.34; 95% CI 1.05 to 1.71)
    • Syncope or dizziness (RR 1.62; 95% CI 1.36 to 1.93)
    • Insomnia (RR 1.66; 95% CI 1.36 to 2.02)
    • Abnormal dreams (RR 4.25; 95% CI 2.57 to 7.04)
  • Serious side-effects and deaths were no more common in the patients taking cholinesterase inhibitors

The reviewers concluded:

There is very little evidence that cholinesterase inhibitors affect progression to dementia or cognitive test scores in mild cognitive impairment. This weak evidence is overwhelmed by the increased risk of adverse events, particularly gastrointestinal. Cholinesterase inhibitors should not be recommended for mild cognitive impairment.


Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD009132. DOI: 10.1002/14651858.CD009132.pub2.

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