Department of Veterans Affairs Health Care System, Stanford University School of Medicine, Palo Alto, California.
Am J Geriatr Psychiatry. 2011 Jul;19(7):635-43. doi: 10.1097/JGP.0b013e31820d92b2.
One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.
One week of ad libitum ambulatory sleep data collection.
At-home collection of sleep data and in-laboratory questionnaire.
Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set.
Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined.
Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance.
It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.
阿尔茨海默病（AD）患者睡眠-觉醒巩固经常出现障碍，其假设原因之一是昼夜节律钟功能障碍。本研究的目的是报告与昼夜节律钟相关基因的相关多态性相关的 AD 患者的睡眠-觉醒功能指标。
1 周的自由活动睡眠数据采集。
在家中进行睡眠数据采集和实验室问卷调查。
两个 AD 参与者队列。队列 1（N=124）：斯坦福大学/退伍军人事务部、国家老龄化研究所阿尔茨海默病核心中心（N=81）和尼斯大学医学院记忆障碍诊所（N=43）招募的可能 AD 个体。队列 2（N=176）：来自阿尔茨海默病神经影像倡议数据集的可能 AD 个体。
通过腕部动作计在队列 1 中连续 7 天获得睡眠-觉醒状态的确定，通过神经精神病学问卷获得队列 2 的确定。两个队列均通过 Illumina Beadstation（加利福尼亚州圣地亚哥的 Illumina）进行基因分型，并检查了 122 个与昼夜节律相关的单核苷酸多态性（SNP）。在队列 1 中，还确定了另一个多态性（per3 中的可变数串联重复）。
调整多重检验后，候选基因 SNP 均与睡眠起始后清醒时间（WASO）无显著相关性，WASO 是睡眠巩固的标志。尽管该研究有足够的能力来确定中等大小的相关性，但我们没有发现可能具有临床相关性的关系。
AD 患者昼夜节律相关 SNP 与 WASO 之间不太可能存在与临床有意义的相关性。
