title: Circadian clock gene polymorphisms and sleep-wake disturbance in Alzheimer disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  One week of ad libitum ambulatory sleep data collection.
  
  
  METHODS
  At-home collection of sleep data and in-laboratory questionnaire.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Veterans Affairs Health Care System, Stanford University School of Medicine, Palo Alto, California. yesavage@stanford.edu
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Yesavage
authors.forename: Art
authors.initials: A
authors.lastname: Noda
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernandez
authors.forename: Leah
authors.initials: L
authors.lastname: Friedman
authors.forename: Jauhtai J
authors.initials: JJ
authors.lastname: Cheng
authors.forename: Jared R
authors.initials: JR
authors.lastname: Tinklenberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Hallmayer
authors.forename: Ruth
authors.initials: R
authors.lastname: O'hara
authors.forename: Renaud
authors.initials: R
authors.lastname: David
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Landsverk
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Zeitzer
mesh_terms: D056044:Actigraphy; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D057906:Circadian Clocks / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D020922:Sleep-Wake Transition Disorders / Q000235:genetics / Q000503:physiopathology*