RESUMEN
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.
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Relojes Circadianos/genética , Trastornos del Sueño del Ritmo Circadiano/genética , Trastornos de la Transición Sueño-Vigilia/fisiopatología , Actigrafía , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Trastornos de la Transición Sueño-Vigilia/genéticaRESUMEN
Veterans who have been deployed to combat often have complex medical histories including some combination of traumatic brain injury (TBI); mental health problems; and other chronic, medically unexplained symptoms (i.e., chronic multisymptom illness [CMI] clusters). How these multiple pathologies relate to functional health is unclear. In the current study, 120 Veterans (across multiple combat cohorts) underwent comprehensive clinical evaluations and completed self-report assessments of mental health symptoms (Patient Health Questionnaire-2 [PHQ-2], PTSD Checklist-Civilian Version [PCL-C]) and functional health (Veterans Rand 36-Item Health Survey). Canonical correlation and regression modeling using split-sample permutation tests revealed that the PHQ-2/PCL-C composite variable (among TBI severity and number of problematic CMI clusters) was the primary predictor of multiple functional health domains. Two subscales, Bodily Pain and General Health, were associated with multiple predictors (TBI, PHQ-2/PCL-C, and CMI; and PHQ-2/PCL-C and CMI, respectively), demonstrating the multifaceted nature of how distinct medical problems might uniquely and collectively impair aspects of functional health. Apart from these findings, however, TBI and CMI were not predictors of any other aspects of functional health. Taken together, our findings suggest that mental health problems might exert ubiquitous influence over multiple domains of functional health. Thus, screening of mental health problems and education and promotion of mental health resources can be important to the treatment and care of Veterans.