Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMR-S975, France.
Mov Disord. 2012 Sep 1;27(10):1230-8. doi: 10.1002/mds.25098. Epub 2012 Aug 22.
Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society.
帕金森病痴呆（PDD）与胆碱能缺陷有关。本报告介绍了乙酰胆碱酯酶抑制剂盐酸多奈哌齐在 PDD 中的疗效和安全性研究。将 550 例 PDD 患者随机分为多奈哌齐（5 或 10mg）或安慰剂组，治疗 24 周。主要终点为阿尔茨海默病评估量表认知分量表（ADAS-cog）和临床医生基于访谈的变化印象加照料者输入（CIBIC+；整体功能）。次要终点为评估执行功能、注意力、日常生活活动（ADL）和行为症状。评估安全性和耐受性。根据预先设定的统计学模型，在意向治疗人群中，多奈哌齐治疗 24 周（终点）后与基线相比，ADAS-cog 平均值变化无显著差异（与安慰剂相比：5mg 组为-1.45，P=0.050；10mg 组为-1.45，P=0.076）。替代 ADAS-cog 分析，从模型中去除治疗-国家交互项，显示多奈哌齐具有显著的、剂量依赖性的获益（与安慰剂相比：5mg 组为-2.08，P=0.002；10mg 组为-3.31，P＜0.001）。与安慰剂相比，仅 10mg 组的 CIBIC+评分有显著改善（3.7 对 3.9，P=0.113；5mg 组；3.6 对 3.9，P=0.040；10mg 组）。次要终点-简易精神状态检查；Delis-Kaplan 执行功能系统；简短注意力测验，代表与 PDD 特别相关的认知功能-均显示多奈哌齐两个剂量均有显著获益（P≤0.007）。ADL 或行为无显著差异。多奈哌齐的不良事件更为常见，但大多为轻度/中度。尽管该研究未达到其预先设定的主要终点，但它提供了证据表明，多奈哌齐可改善 PDD 患者的认知、执行功能和整体状况。耐受性与多奈哌齐已知的安全性特征一致。© 2012 运动障碍学会。
