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Evidence summaries

Cholinesterase Inhibitors for Mild Cognitive Impairment

Cholinesterase inhibitors do probably not have an effect on progression to dementia or cognitive test scores in mild cognitive impairment but may increase the risk of particularly gastrointestinal adverse events. Level of evidence: "C"

Summary

A Cochrane review [Abstract] 1 included 9 RCTs with a total of 5149 patients with mild cognitive impairment (MCI). Few studies used a standard definition for MCI. Donepezil (3 studies), galantamine (4 studies) and rivastigmine (2 studies) were used. The follow-up time varied between 16 weeks and 4 years. Meta-analysis of the 3 studies (based on between 1530 and 2650 patients) 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 RR for conversion at two years was significantly different from unity (0.67; 95% CI 0.55 to 0.83), but this is based on only two studies reported in the same article (n=2048). There was essentially no effect of cholinesterase inhibitors on cognitive test scores. There were significantly more adverse events in the cholinesterase inhibitor groups (RR 1.09; 95% CI 1.02 to 1.16; n=4207), 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).

Comment: The quality of the evidence is downgraded by inconsistency (heterogeneity in patients, interventions and outcomes) and indirectness (short follow-up time).

Clinical comments

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    References

    • Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev 2012;9():CD009132. [PubMed]

Primary/Secondary Keywords