Schmidt R, Hofer E, Bouwman F H, Buerger K, Cordonnier C, Fladby T, Galimberti D, Georges J, Heneka M T, Hort J, Laczó J, Molinuevo J L, O'Brien J T, Religa D, Scheltens P, Schott J M, Sorbi S
Department of Neurology, Medical University of Graz, Graz, Austria.
Eur J Neurol. 2015 Jun;22(6):889-98. doi: 10.1111/ene.12707. Epub 2015 Mar 25.
Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (ChEI) and memantine over ChEI monotherapy in Alzheimer's disease (AD). Our objective was the development of guidelines on the question of whether combined ChEI/memantine treatment rather than ChEI alone should be used in patients with moderate to severe AD to improve global clinical impression (GCI), cognition, behaviour and activities of daily living (ADL).
A systematic review and meta-analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to ChEI monotherapy for GCI [standardized mean difference (SMD) -0.20; 95% confidence interval (CI) -0.31; -0.09], cognitive functioning (SMD -0.27, 95% CI -0.37; -0.17) and behaviour (SMD -0.19; 95% CI -0.31; -0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined ChEI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak.
We suggest the use of a combination of ChEI plus memantine rather than ChEI alone in patients with moderate to severe AD. The strength of this recommendation is weak.
既往研究表明，在阿尔茨海默病（AD）中，胆碱酯酶抑制剂（ChEI）与美金刚联合使用相较于ChEI单药治疗具有临床益处。我们的目标是制定指南，以解决在中度至重度AD患者中，应使用ChEI与美金刚联合治疗还是仅使用ChEI来改善整体临床印象（GCI）、认知、行为及日常生活活动（ADL）的问题。
基于对Cochrane痴呆与认知改善小组登记册ALOIS中的文献检索，进行了随机对照试验的系统评价和荟萃分析，随后根据推荐分级评估、制定与评价（GRADE）系统制定指南。
四项试验的汇总数据包括1549例中度至重度疾病阶段的AD患者，结果表明，与ChEI单药治疗相比，联合治疗对GCI[标准化均数差（SMD）-0.20；95%置信区间（CI）-0.31；-0.09]、认知功能（SMD -0.27，95% CI -0.37；-0.17）和行为（SMD -0.19；95% CI -0.31；-0.07）具有显著益处。行为方面的证据质量高，认知功能和GCI方面为中等，ADL方面为低。在第二轮共识达成程序后，专家小组成员达成了一致意见。ChEI与美金刚联合治疗的有益效果被认为超过不良效果。认知、GCI和ADL方面的证据较弱，因此使用联合治疗的总体推荐力度较弱。
我们建议在中度至重度AD患者中使用ChEI加美金刚的联合治疗而非仅使用ChEI。该推荐的力度较弱。
