Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
J Am Geriatr Soc. 2018 Jan;66(1):170-178. doi: 10.1111/jgs.15069. Epub 2017 Sep 29.
BACKGROUND/OBJECTIVES: To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD).
Systematic review and Bayesian network metaanalysis (NMA).
MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception-March 2016).
Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies.
Any combination of donepezil, rivastigmine, galantamine, or memantine.
Two reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias.
Twenty thousand three hundred forty-three citations were screened, and 142 studies were included (110 RCTs, 21 non-RCTs, 11 cohort studies). NMA found that donepezil (Mini-Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53-2.24), donepezil+memantine (2.59, 95% CrI = 0.12-4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02-4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale-cognitive: MD = -3.29, 95% CrI = -4.57 to -1.99) and galantamine (MD = -2.13, 95% CrI = -3.91 to -0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) improved behavior more than placebo. NMA found that donepezil (MD = -0.32, 95% CrI = -0.46 to -0.19), donepezil+memantine (MD = -0.57, 95% CrI = -0.95 to -0.21), oral rivastigmine (MD = -0.38, 95% CrI = -0.56 to -0.17), and galantamine (MD = -3.79, 95% CrI = -6.98 to -0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine).
An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.
背景/目的：考察用于治疗阿尔茨海默病（AD）的认知增强剂的比较疗效和安全性。
系统评价和贝叶斯网络荟萃分析（NMA）。
MEDLINE、EMBASE、Cochrane 图书馆、CINAHL、Ageline（从建库起至 2016 年 3 月）。
在随机对照试验（RCT）、准 RCT 和非随机研究中患有 AD 的个体。
任何组合的多奈哌齐、利斯的明、加兰他敏或美金刚。
两位审查员独立筛选标题、摘要和全文；提取数据；并评估偏倚风险。
筛选了 23430 个引文，纳入了 142 项研究（110 项 RCT、21 项非 RCT、11 项队列研究）。NMA 发现多奈哌齐（简易精神状态检查：均差（MD）=1.39，95%可信区间（CrI）=0.53-2.24）、多奈哌齐+美金刚（2.59，95% CrI=0.12-4.98）和透皮利斯的明（2.02，95% CrI=0.02-4.08）改善认知的效果优于安慰剂。NMA 发现多奈哌齐（阿尔茨海默病评估量表-认知：MD=-3.29，95% CrI=-4.57 至-1.99）和加兰他敏（MD=-2.13，95% CrI=-3.91 至-0.27）改善认知的效果优于安慰剂。NMA 发现多奈哌齐+美金刚（MD=-5.23，95% CrI=-8.72 至-1.56）改善行为的效果优于安慰剂。NMA 发现多奈哌齐（MD=-0.32，95% CrI=-0.46 至-0.19）、多奈哌齐+美金刚（MD=-0.57，95% CrI=-0.95 至-0.21）、口服利斯的明（MD=-0.38，95% CrI=-0.56 至-0.17）和加兰他敏（MD=-3.79，95% CrI=-6.98 至-0.59）改善整体状况的效果优于安慰剂。NMA 发现加兰他敏降低了死亡率的几率（比值比=0.56，95% CrI=0.36-0.87）。没有药物增加严重不良事件、跌倒或心动过缓的风险。一些药物增加了头痛（口服利斯的明）、腹泻（口服利斯的明、多奈哌齐）、恶心（口服利斯的明、多奈哌齐、加兰他敏）和呕吐（口服利斯的明、多奈哌齐、加兰他敏）的风险。
对涉及 142 项研究的文献进行了全面审查，结果表明，根据最小临床重要差异和总体评价，认知增强剂对认知的影响很小。这些药物似乎是安全的，但这必须谨慎解释，因为试验参与者可能比在临床实践中接受这些药物治疗的患者具有更少的合并症和更少的不良反应。
