Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease
Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease
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DOI：
10.1212/wnl.0b013e3181f6128c
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发表时间：
2010-10-05
期刊：
影响因子：
9.9
通讯作者：
Horak, Fay B.
中科院分区：
文献类型：
--
作者：
Chung, Kathryn A.;Lobb, Brenna M.;Horak, Fay B.
目的：研究中枢胆碱酯酶抑制剂是否会减少患有晚期姿势不稳定的帕金森病 (PD) 受试者的跌倒频率。背景：由于姿势不稳定导致的跌倒是晚期帕金森病 (PD) 的一个重要问题，并且受多巴胺能治疗的影响很小。抗胆碱能药物会增加老年人跌倒的风险。此外，PD 中会发生中枢神经系统胆碱能神经元损失。我们假设乙酰胆碱增强可能会减少 PD 受试者频繁跌倒的情况。方法：我们招募了 23 名 PD 受试者，他们报告每周跌倒或几乎跌倒超过 2 次。在随机、安慰剂对照、交叉设计中，受试者接受 6 周的多奈哌齐或安慰剂治疗，并在各阶段之间进行 3 周的清除。主要结果是明信片上报告的每日跌倒和接近跌倒的情况。次要结局包括平衡信心量表活动、伯格平衡量表、临床总体印象变化、Folstein 简易精神状态检查和统一帕金森病评定量表运动部分的分数。 结果：安慰剂组每天跌倒频率为 0.25 +/- 0.08 (SEM)，而多奈哌齐组为 0.13 +/- 0.03 (p < 0.05)。不同阶段之间险些跌倒的频率没有显着差异。次要结果没有差异；然而，受试者完成的全球变化印象量表有改善的趋势。结论：在 6 周内，服用多奈哌齐的 PD 受试者的病情下降频率大约是服用安慰剂的受试者的一半。对于经常跌倒的 PD 受试者，有必要进行更大规模的胆碱能增强试验。证据分类：本研究提供了 II 类证据，表明多奈哌齐（每天最多 10 mg）比服用安慰剂（每天 0.25 次跌倒，SEM = 0.08，p = 0.049）显着减少 PD 患者的跌倒次数（0.13 次跌倒/天，SEM = 0.03）。神经病学（R）2010；75：1263-1269
Objective: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability.Background: Falling due to postural instability is a significant problem in advancing PD, and is minimally impacted by dopaminergic therapy. Anticholinergic medications increase falling in the elderly. Further, CNS cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine augmentation may reduce frequent falling in subjects with PD.Methods: We enrolled 23 subjects with PD who reported falling or nearly falling more than 2 times per week. In a randomized, placebo-controlled, crossover design, subjects were given 6 weeks of donepezil or placebo with a 3-week washout between phases. The primary outcomes were daily falls and near falls reported on postcards. Secondary outcomes included scores on the Activities of Balance Confidence Scale, Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental State Examination, and the motor section of the Unified Parkinson's Disease Rating Scale.Results: Fall frequency per day on placebo was 0.25 +/- 0.08 (SEM) compared with 0.13 +/- 0.03 on donepezil (p < 0.05). The frequency of near falls was not significantly different between phases. The secondary outcomes did not differ; however, there was a trend to improvement on the subject-completed Global Impression of Change scale.Conclusions: Subjects with PD fell approximately half as often during the 6 weeks on donepezil than on placebo. Larger trials of cholinergic augmentation are warranted in subjects with PD with frequent falls.Classification of evidence: This study provides Class II evidence that donepezil (maximum 10 mg per day) significantly reduced the number of falls in patients with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day, SEM = 0.08, p = 0.049). Neurology (R) 2010;75:1263-1269