Russ Tom C, Morling Joanne R
Alzheimer Scotland Dementia Research Centre, Edinburgh, UK.
Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD009132. doi: 10.1002/14651858.CD009132.pub2.
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.
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.
Double-blind, placebo-controlled randomised trials of any cholinesterase inhibitor in people with mild cognitive impairment.
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.
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.
轻度认知障碍被认为是痴呆的临床前期，但它是一个异质性群体，预后各不相同。
评估胆碱酯酶抑制剂对轻度认知障碍患者的安全性和疗效。
从Cochrane痴呆与认知改善小组的专业注册库中识别试验，该注册库会定期从主要医疗保健数据库（MEDLINE、EMBASE、CINAHL、PsycINFO和Lilacs）以及试验注册库和灰色文献中更新。
任何胆碱酯酶抑制剂针对轻度认知障碍患者的双盲、安慰剂对照随机试验。
从纳入研究的已发表报告中提取数据，在适当情况下通过荟萃分析进行合并，并估计治疗效果和不良事件风险。
本综述纳入了9项研究（来自8篇已发表报告），共5149例轻度认知障碍患者（无论如何定义）。由于试验时长不同，结果的合并有限。对3项报告转化为痴呆情况的研究进行荟萃分析，未发现有力证据表明胆碱酯酶抑制剂在1年、2年或3年时对痴呆进展有有益作用。两年时转化的风险比（RR）显著不同于1（0.67；95%置信区间（CI）0.55至0.83），但这仅基于同一篇文章中报告的两项研究。胆碱酯酶抑制剂对认知测试分数基本没有影响。基于4207例患者的结果，胆碱酯酶抑制剂组的不良事件明显更多（RR 1.09；95%CI 1.02至1.16），但严重不良事件或死亡情况没有更多。胃肠道副作用更为常见（腹泻：RR 2.10；95%CI 1.30至3.39；恶心：RR 2.97；95%CI 2.57至3.42；呕吐：RR 4.42；95%CI 3.23至6.05）。两组中心脏问题的发生可能性没有差异（RR 0.71；95%CI 0.25至2.02）。胆碱酯酶抑制剂组报告明显更频繁的其他副作用包括肌肉痉挛/腿部抽筋（RR 7.52；95%CI 4.34至13.02）、头痛（RR 1.34；95%CI 1.05至1.71）、晕厥或头晕（RR 1.62；95%CI 1.36至1.93）、失眠（RR 1.66；95%CI 1.36至2.02）和异常梦境（RR 4.25；95%CI 2.57至7.04）。
几乎没有证据表明胆碱酯酶抑制剂会影响轻度认知障碍向痴呆的进展或认知测试分数。这种微弱的证据被不良事件风险增加所掩盖，尤其是胃肠道不良事件。不建议将胆碱酯酶抑制剂用于轻度认知障碍。
