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  • Title: 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.
    Author: Spira AP, Zipunnikov V, Raman R, Choi J, Di J, Bai J, Carlsson CM, Mintzer JE, Marshall GA, Porsteinsson AP, Yaari R, Wanigatunga SK, Kim J, Wu MN, Aisen PS, Sperling RA, Rosenberg PB.
    Journal: Sleep Adv; 2021; 2(1):zpab015. PubMed ID: 34661109.
    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.
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