Cooke Jana R, Loredo Jose S, Liu Lianqi, Marler Matthew, Corey-Bloom Jody, Fiorentino Lavinia, Harrison Tamara, Ancoli-Israel Sonia
Department of Medicine, University of California, San Diego, California, USA.
Drugs Aging. 2006;23(6):503-11. doi: 10.2165/00002512-200623060-00005.
Studies suggest that some acetylcholinesterase inhibitors (AChEIs) increase rapid eye movement (REM) sleep and nightmares in patients with Alzheimer's disease (AD) but few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs.
76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed.
AChEI therapy had a significant effect on the percentage of stage 1 (p = 0.01) and stage 2 (p = 0.03) sleep. Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters.
Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest that sleep architecture may be affected by the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD.
研究表明，某些乙酰胆碱酯酶抑制剂（AChEIs）会增加阿尔茨海默病（AD）患者的快速眼动（REM）睡眠和噩梦发生率，但很少有研究探讨其对其他睡眠参数的影响。本研究的目的是检验服用不同AChEIs的AD患者的睡眠结构差异。
76名轻度至中度AD患者（51名男性，25名女性）[平均年龄 = 78.2岁；标准差 = 7.7]接受了用药史筛查以及多导睡眠图检查，以确定每个睡眠阶段的百分比。参与者根据所使用的AChEI分为以下几组：多奈哌齐组（n = 41）、加兰他敏组（n = 15）、卡巴拉汀组（n = 8）或未使用AChEI组（n = 12）。进行了一般单变量线性模型分析。
AChEI治疗对1期（p = 0.01）和2期（p = 0.03）睡眠的百分比有显著影响。多奈哌齐组患者的1期睡眠百分比显著低于加兰他敏组患者（分别为平均 = 17.3%，标准差 = 11.7与29.2%，标准差 = 15.0；p = 0.01），但在这方面，多奈哌齐组与卡巴拉汀组（平均 = 25.0%，标准差 = 12.3）或未使用AChEI组（平均 = 27.6%，标准差 = 17.7）之间无显著差异。其他组之间1期睡眠百分比无显著差异。多奈哌齐组患者的2期睡眠百分比也显著高于未使用AChEI组患者（分别为平均 = 63.6%，标准差 = 14.4与51.4%，标准差 = 16.9；p = 0.04），但多奈哌齐组与加兰他敏组（平均 = 56.5%，标准差 = 8.7）或卡巴拉汀组（平均 = 59.9%，标准差 = 8.4）之间无显著差异。各组在REM睡眠百分比或其他睡眠参数方面无显著差异。
本研究中（根据AChEI治疗分类）的AD患者亚组在1期和2期睡眠量方面存在差异，多奈哌齐治疗组的1期睡眠百分比最低，2期睡眠百分比最高。各组之间REM睡眠量无显著差异。我们的数据表明，多奈哌齐的使用可能会影响AD患者的睡眠结构。由于样本量小，本研究未得出此结论，但AChEIs对睡眠结构可能存在类效应。需要进行双盲、安慰剂对照研究，以更好地理解因果关系以及每种AChEI对AD患者睡眠结构的影响。
