Evaluating a Novel 24-Hour Rest/Activity Rhythm Marker of Preclinical β-Amyloid Deposition

Abstract 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 vs. 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 (FOSR) 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 PM-3:30 PM when using less conservative pointwise confidence intervals (CIs) and from 1:30 PM-2:30 PM using more conservative, simultaneous CIs. Further, Aβ+ participants had higher day-to-day variability in activity from 9:00 AM-11:30 AM and lower variability from 1:30 PM-4:00 PM and 7:30 PM-10:30 PM according to pointwise CIs, and lower variability from 8:30 PM-10:00 PM 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 Aβdeposition and if they predict clinical dementia and agitation in the afternoon/evening (i.e., “sundowning”).