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).
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