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

Sleep. 2024 May 10;47(5):zsae037. doi: 10.1093/sleep/zsae037.

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+ 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").

Keywords: Alzheimer’s; Circadian; actigraphy; biomarker; dementia; sleep.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actigraphy* / methods
  • Actigraphy* / statistics & numerical data
  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides* / metabolism
  • Aniline Compounds
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Circadian Rhythm / physiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Positron-Emission Tomography* / methods
  • Rest / physiology
  • Sleep / physiology
  • Thiazoles

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Biomarkers
  • Thiazoles
  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole