Efficacy of donepezil in mild cognitive impairment - A randomized placebo-controlled trial
Efficacy of donepezil in mild cognitive impairment - A randomized placebo-controlled trial
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DOI：
10.1212/01.wnl.0000134664.80320.92
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发表时间：
2004-08-24
期刊：
影响因子：
9.9
通讯作者：
Richardson, S
中科院分区：
文献类型：
--
作者：
Salloway, S;Ferris, S;Richardson, S
目的：评价乙酰胆碱酯酶抑制剂多奈哌齐在轻度认知功能障碍（MCI）患者中的疗效和安全性。方法：270例MCI患者参加了一项为期24周的多中心、随机、双盲、安慰剂对照研究。患者随机接受多奈哌齐（n=133; 5 mg/天，持续42天，随后强制剂量递增至10 mg/天）或安慰剂（n=137）。主要疗效指标为纽约大学（NYU）段落延迟回忆测试和阿尔茨海默病（AD）合作研究临床医生对MCI的总体印象变化（ADCS CGIC-MCI）。次要疗效指标包括改良AD评估量表-认知子量表（ADAS-cog）、患者总体评估（PGA）和其他神经心理学指标。在意向治疗（ITT）和完全可评价（FE）人群中进行疗效分析。结果如下：在ITT人群中，NYU段落回忆测试和ADCS CGIC-MCI的主要疗效指标未显示出显著的治疗效应。一些次要措施显示有利于多奈哌齐的效果。更多多奈哌齐治疗的患者在ADAS-cog总分、注意力和精神速度测试以及PGA评分方面表现出改善。多奈哌齐治疗的患者比安慰剂治疗的患者发生不良事件更多，其中大多数是轻度至中度和短暂的。结论：虽然在主要疗效指标中未观察到显著的治疗效果，但次要指标的结果表明，多奈哌齐治疗MCI患者的进一步评价有希望。
Objective: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). Methods: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n=133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n=137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. Results: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. Conclusion: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.