中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (5): 805-816.doi: 10.4103/1673-5374.249228

• 原著:退行性病与再生 • 上一篇    下一篇

认知增强剂治疗血管性认知障碍的疗效和安全性：系统评价和贝叶斯网络荟萃分析

  

  • 出版日期:2019-05-15 发布日期:2019-05-15
  • 基金资助:

    辽宁省自然科学基金项目（20170541036）

Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis

Bo-Ru Jin, Hua-Yan Liu   

  1. Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, China
  • Online:2019-05-15 Published:2019-05-15
  • Contact: Hua-Yan Liu, PhD, liuhuayancmu@163.com.
  • Supported by:

    The study was supported by the Natural Science Foundation of Liaoning Province of China, No. 20170541036 (to HYL).

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摘要：

目的：评估和比较认知增强剂（多奈哌齐、加兰他敏、利凡斯的明和美金刚）对血管性认知障碍患者认知、行为、神经功能和整体状态的疗效和安全性。
资料来源：检索Pubmed，EMBASE，Cochrane Methodology Register，Cochrane Central Control of Controlled Trials和CINAHL从建库到2018年1月收录多奈哌齐、加兰他敏、利凡斯的明和美金刚治疗血管性认知障碍的临床研究。
资料选择：选择将多奈哌齐、加兰他敏、利凡斯的明和美金刚中的一种作为血管性认知障碍治疗的单一方法进行的安慰剂随机对照试验，使用随机效应模型进行传统的成对荟萃分析，使用R 3.0.3版中的GeMTC和JAGS软件包进行贝叶斯网络荟萃分析。
结局评价指标：通过阿尔茨海默病评价量表——认知分表、简易智力状态检查量表、神经精神问卷评估治疗的疗效。以医师面谈印象变化加监护人提供信息量表、日常生活能力量表、临床痴呆评定量表、死亡率、不良事件评估治疗的安全性。
结果：从1717项研究中纳入了12项随机对照试验。在疗效方面：多奈哌齐和利凡斯的明的简易智力状态检查量表评分高于安慰剂(MD=0.77, 95%CrI=0.25—1.32；MD=1.05，95%CrI=0.18—1.79)。多奈哌齐、加兰他敏和美金刚的阿尔茨海默病评价量表——认知分表评分高于安慰剂(MD=-1.30, 95%Crl=-2.27—-0.42；MD=-1.67, 95%Crl=-3.36—-0.06；MD=-2.27，95%Crl=-3.91—-0.53)。美金刚医师面谈印象变化加监护人提供信息量表评分高于安慰剂(MD=2.71, 95%CrI=1.05-7.29)。安全性方面：多奈哌齐10mg可增加不良事件的总风险(OR=3.04, 95%CrI=1.86-5.41)，加兰他敏增加恶心的风险（OR = 5.64,95％Crl = 1.31-26.71），利凡斯的明增加呕吐的风险（OR = 16.80,95％Crl = 1.78-319.26）。4种药物对严重不良反应发生率、死亡率、脑血管疾病发生率和腹泻发生率没有明显增加。
结论：多奈哌齐、加兰他敏和美金刚、可明显改善血管性认知障碍患者的认知功能，其中美金刚还可改善患者整体状态，且这种药物均是安全的且耐受性良好。

orcid: 0000-0001-9806-9003 (Hua-Yan Liu)

关键词: 血管性认知障碍, 血管性痴呆, 药物治疗, 胆碱酯酶抑制剂, 多奈哌齐, 加兰他敏, 利凡斯的明, 美金刚, 系统评价, 贝叶斯网络荟萃分析

Abstract:

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers (donepezil, galan¬tamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.
Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Meth¬odology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health (CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.
Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network me¬ta-analysis was conducted.
Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer’s Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician’s In¬terview-Based Impression of Change Scale Plus Caregiver’s Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events (TAEs), serious adverse events (SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents (CVAs).
Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine (mean difference (e) = –0.77, 95% confidence interval (CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine (MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer’s Disease Assessment Scale–cognitive scores compared with placebo. Memantine (MD = 2.71, 95% CI: 1.05–7.29) improved global status (Clinician’s Interview-Based Impression of Change Scale Plus Caregiver’s Input) more than the place¬bo. Safety results revealed that donepezil 10 mg (odds ratio (OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine (OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine (OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.
Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Me¬mantine can provide significant efficacy in global status. They are all safe and well tolerated.

Key words: nerve regeneration, vascular cognitive impairment, vascular dementia, pharmacotherapy, cholinesterase inhibitors, donepezil, galantamine, rivastigmine, memantine, systematic review, Bayesian network meta-analysis, neural regeneration