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

Adam P Spira; Vadim Zipunnikov; Rema Raman; Jiyoon Choi; Junrui Di; Jiawei Bai; Cynthia M Carlsson; Jacobo E Mintzer; Gad A Marshall; Anton P Porsteinsson; Roy Yaari; Sarah K Wanigatunga; John Kim; Mark N Wu; Paul S Aisen; Reisa A Sperling; Paul B Rosenberg

doi:10.1093/sleepadvances/zpab015

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

Sleep Adv. 2021 Sep 19;2(1):zpab015. doi: 10.1093/sleepadvances/zpab015. eCollection 2021.

Authors

Adam P Spira^{1

2

3}, Vadim Zipunnikov¹, Rema Raman⁴, Jiyoon Choi⁴, Junrui Di¹, Jiawei Bai¹, Cynthia M Carlsson⁵, Jacobo E Mintzer^{6

7}, Gad A Marshall⁸, Anton P Porsteinsson⁹, Roy Yaari¹⁰, Sarah K Wanigatunga¹, John Kim², Mark N Wu², Paul S Aisen⁴, Reisa A Sperling⁸, Paul B Rosenberg²

Affiliations

¹ Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
² Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Johns Hopkins Center on Aging and Health, Baltimore, MD, USA.
⁴ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
⁵ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁶ Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
⁷ Lowcountry Center for Veterans Research, South Carolina Institute for Brain Health, Charleston, SC, USA.
⁸ Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
¹⁰ Eli Lilly and Company, Indianapolis, IN, USA.

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.

Keywords: Alzheimer’s disease; actigraphy; activity; amyloid; circadian; cognitive; rhythm; sleep; wrist.

Abstract

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