Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK.
Int J Geriatr Psychiatry. 2010 Mar;25(3):305-13. doi: 10.1002/gps.2340.
To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD).
International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.7 +/- 0.3) with a diagnosis of possible or probable VaD and without a diagnosis of Alzheimer's disease, who were medically stable and had completed one of two double-blind studies. All patients received donepezil 5 mg/day for the first 6 weeks, then 10 mg/day (clinician approval required). Assessments were performed at week 6 and every 12 weeks thereafter. The main outcome measure was the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog). Safety/tolerability measures included adverse events (AEs) and physical and laboratory evaluations.
Of 1219 eligible patients, 885 (72.6%) were enrolled, of which 707 (79.9%) completed the study; 127 (14.4%) patients discontinued due to AEs. A mean reduction (0.6-1.15 points) from double-blind study baseline score to week 54 (end of open-label study) on the ADAS-cog was observed for patients who received donepezil continuously for 54 weeks. ADAS-cog scores remained stable in the group that initiated donepezil treatment during the extension study. Most common donepezil-related AEs were nausea (occurring in 5.3%) and diarrhoea (8.8%); no unexpected AEs attributable to donepezil occurred.
These data suggest that donepezil improves cognition for up to 54 weeks in patients with VaD. Patients initiating donepezil in this extension study did not perform as well on the primary outcome measure as those initiating donepezil in the double-blind study.
确定多奈哌齐治疗血管性痴呆（VaD）患者的长期耐受性和疗效。
两项为期 24 周、随机、双盲、安慰剂对照研究的国际、多中心、开放性、30 周扩展研究。参与者为有活动能力的成年人（59%为女性；平均年龄 74.7+/-0.3），诊断为可能或很可能的 VaD，没有阿尔茨海默病的诊断，身体状况稳定，并且完成了两项双盲研究中的一项。所有患者在前 6 周接受多奈哌齐 5mg/天治疗，然后接受 10mg/天治疗（需要临床医生批准）。在第 6 周和此后每 12 周进行评估。主要观察指标是阿尔茨海默病评估量表-认知分量表（ADAS-cog）。安全性/耐受性测量包括不良事件（AE）和身体及实验室评估。
在 1219 名符合条件的患者中，885 名（72.6%）入选，其中 707 名（79.9%）完成了研究；127 名（14.4%）患者因 AE 而停药。接受多奈哌齐连续治疗 54 周的患者，从双盲研究基线评分到第 54 周（开放标签研究结束），ADAS-cog 的平均评分降低（0.6-1.15 分）。在扩展研究期间开始接受多奈哌齐治疗的患者，ADAS-cog 评分保持稳定。最常见的多奈哌齐相关 AE 是恶心（发生在 5.3%的患者中）和腹泻（8.8%）；没有发生与多奈哌齐相关的意外 AE。
这些数据表明，多奈哌齐可改善 VaD 患者的认知功能长达 54 周。在这项扩展研究中开始接受多奈哌齐治疗的患者，在主要终点上的表现不如在双盲研究中开始接受多奈哌齐治疗的患者。
