Evaluating a novel 24-hour rest/activity rhythm marker of preclinical β-amyloid deposition

Adam P. Spira, Fangyu Liu, Vadim Zipunnikov, Murat Bilgel, Jill A. Rabinowitz, Yang An, Junrui Di, Jiawei Bai, Sarah K. Wanigatunga, Mark N. Wu, Brendan P. Lucey, Jennifer A. Schrack, Amal A. Wanigatunga, Paul B. Rosenberg, Eleanor M. Simonsick, Keenan A. Walker, Luigi Ferrucci, Susan M. Resnick

Research output: Contribution to journalArticlepeer-review


Study Objectives: To compare sleep and 24-hour rest/activity rhythms (RARs) between cognitively normal older adults who are β-amyloid-positive (Aβ+) or Aβ- and replicate a novel time-of-day-specific difference between these groups identified in a previous exploratory study. Methods: We studied 82 cognitively normal participants from the Baltimore Longitudinal Study of Aging (aged 75.7 ± 8.5 years, 55% female, 76% white) with wrist actigraphy data and Aβ+ versus Aβ- status measured by [11C] Pittsburgh compound B positron emission tomography. RARs were calculated using epoch-level activity count data from actigraphy. We used novel, data-driven function-on-scalar regression analyses and standard RAR metrics to cross-sectionally compare RARs between 25 Aβ+ and 57 Aβ- participants. Results: Compared to Aβ- participants, Aβ+ participants had higher mean activity from 1:00 p.m. to 3:30 p.m. when using less conservative pointwise confidence intervals (CIs) and from 1:30 p.m. to 2:30 p.m. using more conservative, simultaneous CIs. Furthermore, Aβ+ participants had higher day-to-day variability in activity from 9:00 a.m. to 11:30 a.m. and lower variability from 1:30 p.m. to 4:00 p.m. and 7:30 p.m. to 10:30 p.m. according to pointwise CIs, and lower variability from 8:30 p.m. to 10:00 p.m. using simultaneous CIs. There were no Aβ-related differences in standard sleep or RAR metrics. Conclusions: Findings suggest Aβ+ older adults have higher, more stable day-to-day afternoon/evening activity than Aβ- older adults, potentially reflecting circadian dysfunction. Studies are needed to replicate our findings and determine whether these or other time-of-day-specific RAR features have utility as markers of preclinical Aβ deposition and if they predict clinical dementia and agitation in the afternoon/evening (i.e. "sundowning").

Original languageEnglish (US)
Article numberzsae037
Issue number5
StatePublished - May 1 2024


  • Alzheimer's
  • Circadian
  • actigraphy
  • biomarker
  • dementia
  • sleep

ASJC Scopus subject areas

  • General Medicine


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