Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies
Year: 2021
Type: article
Abstract: Study Objectives To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer’s disease (AD). Methods Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ−) cognitively unimpaired participants (mean age = 71.3 ± 4.6 years, 59% women) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, respectively, wore actigraphs for 5.66 ± 0.88 24-hour periods. We computed standard sleep parameters, standard RAR metrics (mean estimating statistic of rhythm, amplitude, acrophase, interdaily stability, intradaily variability, relative amplitude), and performed a novel RAR analysis (function-on-scalar regression [FOSR]). Results We were unable to detect any differences between Aβ+ and Aβ− participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aβ+ participants had lower activity levels than Aβ− participants in the late night through early morning (11:30 pm to 3:00 am), and higher levels in the early morning (4:30 am to 8:30 am) and from midday through late afternoon (12:30 pm to 5:30 pm; all p < .05). Aβ+ participants also had higher variability in activity across days from 9:30 pm to 1:00 am and 4:30 am to 8:30 am, and lower variability from 2:30 am to 3:30 am (all p < .05). Conclusions Although we found no association of preclinical AD with standard actigraphic sleep or RAR metrics, a novel data-driven analytic method identified temporally “local” RAR alterations in preclinical AD.
Source: SLEEP Advances
Institutions: Johns Hopkins University, University of Southern California, University of Wisconsin–Madison, Ralph H. Johnson VA Medical Center, Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, University of Rochester Medicine, University of Rochester, Eli Lilly (United States)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,750
Funders: U.S. Department of Defense, Alzheimer's Association, Eli Lilly and Company, Brigham and Women's Hospital, Biogen, University of Southern California, ACADIA Pharmaceuticals, GHR Foundation, Eisai, Grifols, National Institutes of Health, Genentech, Avid Radiopharmaceuticals, National Institute on Aging, National Institute of Mental Health
Awards: Decoding neural systems underlying anosognosia for memory loss in aging and Alzheimer's disease, Characterizing the evolution of Subjective Cognitive Decline in preclinical Alzheimer's disease, Novel automated performance-based ADL outcomes for early AD clinical trials, G2298519484, Actigraphic assessment of sleep quality in the A4 trial, G2378349129, G4123117676, Wisconsin Registry for Alzheimer's Prevention, Circadian rhythm disturbance and agitation in Alzheimer's disease, Longitudinal Evaluation of Amyloid Risk and Neurodegeneration, G5110839, G5515000080, ARMADA: Advancing Reliable Measurement in Alzheimer's Disease and cognitive Aging, Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study, G6115228702, The ARIC study of midlife sleep and late-life brain amyloid, G6743890111, Di-Leu-enabled multiplexed quantitation for biomarker discovery and validation in Alzheimer's disease, Investigation of silent mesial temporal lobe hyperexcitability in Alzheimer's disease, Poor Sleep Altered Circadian Rhythms and Alzheimers Disease, Stress Mental Disorders Accelerated Aging and Dementia a 35 year Cohort Study, G7855923974, Alzheimer's Disease Cooperative Study, G8241775203, G8365114119, G8596277002, G8859167876, Neural Correlates of Apathy Across the Alzheimer's Disease Continuum, The Longitudinal Course of Imaging Biomarkers in People At Risk for Alzheimer’s Disease, Alzheimer's Clinical Trials Consortium (ACTC), Impact of Amyloid and Tau on the Aging Brain: The Harvard Aging Brain Study, Johns Hopkins Alzheimer's Disease Research Center, Wisconsin Alzheimer's Disease Research Center, Wisconsin longitudinal study: Initial lifetime's impact on Alzheimer's disease and related disorders (WLS-ILIAD)
OpenAlex ID: W3199111570