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

Study Objectives To compare sleep and 24-hour rest/activity rhythms (RARs) between cognitively normal older adults who are beta-amyloid-positive (A beta+) or A beta- 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 A beta+ versus A beta- 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 A beta+ and 57 A beta- participants.Results Compared to A beta- participants, A beta+ 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, A beta+ 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 A beta-related differences in standard sleep or RAR metrics.Conclusions Findings suggest A beta+ older adults have higher, more stable day-to-day afternoon/evening activity than A beta- 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 A beta deposition and if they predict clinical dementia and agitation in the afternoon/evening (i.e. "sundowning"). Graphical Abstract