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.

STUDY OBJECTIVES: To examine in a subsample at the screening phase of a clinical trial of a ß-amyloid (Aß) 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 Aß-positive (Aß+) and 33 Aß-negative (Aß-) 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 Aß+ and Aß- participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aß+ participants had lower activity levels than Aß- 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). Aß+ 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.