One of the hypothesized causes of the breakdown in sleep/wake consolidation often occurring in individuals with Alzheimer’s disease (AD) is 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 NIA 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 (ADNI) data set.
Determination of sleep/wake state was obtained by wrist actigraphy data for seven days in Cohort 1 and by the Neuropsychiatric Inventory (NPI-Q) for Cohort 2. Both cohorts were genotyped using an Illumina Beadstation and 122 circadian-related 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 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.
Keywords: Alzheimer’s Disease, Sleep/wake Disturbances, Circadian Rhythm