Sobów Tomasz, Kłoszewska Iwona
Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych, Uniwersytet Medyczny, Czechosłowacka 8/10, 92-216 Łódź.
Neurol Neurochir Pol. 2007 Jan-Feb;41(1):13-21.
Despite being commonly regarded as an initial stage of dementia (particularly of Alzheimer's type, AD), mild cognitive impairment (MCI) is usually not treated and no recommendations for management have been established. Cholinesterase inhibitors have been proposed to halt the progression of MCI to AD and several randomized controlled studies (RCT) have been undertaken to prove this hypothesis. Here we have analyzed the results of RCT of ChEI in MCI.
Four long-term RCT of ChEI in MCI were identified. A meta-analysis was conducted with the Mantel-Haenszel method using a fixed model. We compared a major parameter of efficacy (the proportion of those who progressed to dementia within two years) and two parameters of safety, i.e. the total number of adverse events and the number of adverse events leading to drug discontinuation.
The use of ChEI resulted in approximately 24% reduction of risk of conversion from MCI to dementia at the cost of more than 50% increase of adverse events and more than 130% increase of adverse events leading to drug discontinuation, as compared to placebo. Moreover, in the case of galantamine a considerable increase in deaths was observed in the active treatment group; whether this outcome is a class effect of all ChEI or is limited to galantamine cannot be established due to the lack of data from donepezil and rivastigmine trials.
Because of the questionable efficacy : risk ratio, we believe that it is too early to recommend ChEI in MCI. The sine qua non condition is to establish the factors that predict the risk of conversion from MCI to AD.
尽管轻度认知障碍（MCI）通常被视为痴呆（尤其是阿尔茨海默病类型，AD）的初始阶段，但通常不对其进行治疗，且尚未制定管理建议。有人提出使用胆碱酯酶抑制剂来阻止MCI进展为AD，并已开展了多项随机对照研究（RCT）来证实这一假设。在此，我们分析了胆碱酯酶抑制剂治疗MCI的RCT结果。
确定了四项胆碱酯酶抑制剂治疗MCI的长期RCT。采用固定模型，用Mantel-Haenszel方法进行荟萃分析。我们比较了一个主要疗效参数（两年内进展为痴呆的患者比例）和两个安全性参数，即不良事件总数以及导致停药的不良事件数量。
与安慰剂相比，使用胆碱酯酶抑制剂使MCI转化为痴呆的风险降低了约24%，但代价是不良事件增加了50%以上，导致停药的不良事件增加了130%以上。此外，在加兰他敏治疗组中，观察到活性治疗组死亡人数显著增加；由于缺乏多奈哌齐和卡巴拉汀试验的数据，无法确定这一结果是所有胆碱酯酶抑制剂的类效应还是仅限于加兰他敏。
鉴于疗效与风险比存在疑问，我们认为在MCI中推荐使用胆碱酯酶抑制剂为时过早。当务之急是确定预测MCI转化为AD风险的因素。
