Cholinesterase inhibitors for mild cognitive impairment

  • Review
  • Intervention




Mild cognitive impairment is hypothesised to represent a pre-clinical stage of dementia but forms a heterogeneous group with variable prognosis.


To assess the safety and efficacy of cholinesterase inhibitors in people with mild cognitive impairment.

Search methods

Trials were identified from the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, which is frequently updated from the major healthcare databases (MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs) as well as trial registers and grey literature.

Selection criteria

Double-blind, placebo-controlled randomised trials of any cholinesterase inhibitor in people with mild cognitive impairment.

Data collection and analysis

Data were extracted from the published reports of the included studies, combined by meta-analysis where appropriate, and treatment efficacy and risk of adverse events were estimated.

Main results

Nine studies (from eight published reports) of 5149 individuals with mild cognitive impairment (however defined) were included in the review. Limited pooling of results was possible owing to different lengths of trials. Meta-analysis of the three studies reporting conversion to dementia gives no strong evidence of a beneficial effect of cholinesterase inhibitors on the progression to dementia at one, two or three years. The risk ratio (RR) for conversion at two years was significantly different from unity (0.67; 95% confidence interval (CI) 0.55 to 0.83), but this is based on only two studies reported in the same article. There was essentially no effect of cholinesterase inhibitors on cognitive test scores.

Based on the results from 4207 individuals, there were significantly more adverse events in the cholinesterase inhibitor groups (RR 1.09; 95% CI 1.02 to 1.16), but no more serious adverse events or deaths. Gastrointestinal side effects were much more common (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). Other side effects reported significantly more often in the cholinesterase inhibitor group were 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) and abnormal dreams (RR 4.25; 95% CI 2.57 to 7.04).

Authors' conclusions

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.








主要な医療データベース(MEDLINE、EMBASE、CINAHL、PsycINFO及びLilacs)により頻繁に更新されるCochrane Dementia and Cognitive Improvement Group's Specialised Register並びに試験登録、灰色文献から試験を同定した。






軽度認知障害(但し確定した例)患者5,149名を含む9件の試験 (8件の発表済み報告書から得る)をレビューに含めた。試験の実施期間が各々異なるため、結果の統合は限られていた。認知症への移行を報告している3件の試験のメタアナリシスでは、1年目、2年目又は3年目に認知症へ進展することに対して、コリンエステラーゼ阻害薬が有益な効果を持つという強力なエビデンスは得られなかった。2年目に認知症へ移行するリスク比(RR)は全体として有意差を示したが[0.67、95%信頼区間(CI)0.55~0.83)]、この結果は同一の論文に報告された2件の試験のみに基づいたものである。 認知機能検査のスコアへのコリンエステラーゼ阻害薬の効果は基本的にまったく認められなかった。 4,207名の患者からの結果によれば、コリンエステラーゼ阻害薬投与群では有意に有害事象が多かったが(RR 1.09、95%CI 1.02~1.16)、重篤な有害事象又は死亡例はなかった。胃腸系の副作用はそれよりはるかに頻度が高かった(下痢:RR 2.10、95%CI 1.30~3.39;悪心:RR 2.97、95%CI 2.57~3.42;嘔吐:RR 4.42、95%CI 3.23~6.05)。 いずれの群も心合併症はそれほど多くないようであった(RR 0.71、 95%CI 0.25~2.02)。コリンエステラーゼ阻害薬投与群に有意に高頻度であると報告されたその他の副作用は、筋けいれん/こむらがえり(RR 7.52、95%CI 4.34~13.02)、頭痛(RR 1.34、95%CI 1.05~1.71)、失神又はめまい(RR 1.62、95%CI 1.36~1.93)、不眠症(RR 1.66、95%CI 1.36~2.02)及び異常な夢(RR 4.25、95%CI 2.57~7.04)であった。




Translated by: MINDS

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Plain language summary

Anti-dementia drugs for people with memory problems but without dementia

Dementia is a very common condition and, with ageing populations, will only increase in importance in the coming years. Early diagnosis and treatment help people with dementia stay independent and living at home for longer. Cholinesterase inhibitor ('anti-dementia') drugs are used to treat people with Alzheimer's disease (the most common cause of dementia) and can be started as soon as dementia is diagnosed. However, it is not clear whether they are helpful, or indeed safe, in people who have some memory problems but who do not have dementia. It is extremely difficult to predict who will go on to develop dementia from this group of people and some will even get better and their memory return to normal. There is very little evidence that these drugs prevent the development of dementia over three years and people taking them experience a number of side effects including nausea, vomiting and diarrhoea, as well as muscle spasms/leg cramps and abnormal dreams.





Translated by: MINDS

Translation supported by: