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Am J Geriatr Psychiatry. 2011 Jul;19(7):635-43. doi: 10.1097/JGP.0b013e31820d92b2.

Circadian clock gene polymorphisms and sleep-wake disturbance in Alzheimer disease.

Author information

  • 1Department of Veterans Affairs Health Care System, Stanford University School of Medicine, Palo Alto, California. yesavage@stanford.edu

Abstract

OBJECTIVES:

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.

DESIGN:

One week of ad libitum ambulatory sleep data collection.

SETTING:

At-home collection of sleep data and in-laboratory questionnaire.

PARTICIPANTS:

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.

MEASUREMENTS:

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.

RESULTS:

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.

CONCLUSIONS:

It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

PMID:
21709609
[PubMed - indexed for MEDLINE]
PMCID:
PMC3128424
Free PMC Article
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