Krupp L B, Christodoulou C, Melville P, Scherl W F, MacAllister W S, Elkins L E
Department of Neurology, State University of New York at Stony Brook, HSC T12-020, Stony Brook, NY 11794-8121, USA.
Neurology. 2004 Nov 9;63(9):1579-85. doi: 10.1212/01.wnl.0000142989.09633.5a.
To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS).
This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change.
Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010).
Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.
确定多奈哌齐治疗多发性硬化症（MS）记忆和认知功能障碍的效果。
这项单中心双盲安慰剂对照临床试验评估了69例有认知障碍的MS患者，他们被随机分配接受为期24周的多奈哌齐（每日10毫克）或安慰剂治疗。患者在基线和治疗24周后接受神经心理学评估。主要结局是选择性提醒测试（SRT）中言语学习和记忆的变化。次要结局包括其他认知功能测试、患者报告的记忆变化以及临床医生报告的认知变化印象。
与安慰剂相比，多奈哌齐治疗的患者在SRT上的记忆表现有显著改善（p = 0.043）。在控制了包括年龄、扩展残疾状态量表、基线SRT分数、阅读能力、MS亚型和性别等各种协变量后，多奈哌齐的益处仍然显著。多奈哌齐治疗的患者在其他认知测试中没有显示出显著改善，但报告记忆改善的可能性是安慰剂组患者的两倍多（p = 0.006）。临床医生也报告说，多奈哌齐治疗的患者认知改善的人数几乎是安慰剂组的两倍（p = 0.036）。尽管报告异常/异常梦境的多奈哌齐受试者（34.3%）比安慰剂受试者（8.8%）多（p = 0.010），但未发生与研究药物相关的严重不良事件。
在一项单中心临床试验中，多奈哌齐改善了初始认知障碍的MS患者的记忆。有必要对多奈哌齐在MS中的作用进行更大规模的多中心研究，以便更明确地评估这种干预措施的疗效。
