0779 24-Hour Rest-Activity Rhythm and Alzheimer’s Disease Biomarkers in Adults with Down Syndrome

Abstract Introduction Little is known about circadian rhythm disruption and Alzheimer’s disease (AD) biomarkers in adults with Down syndrome (DS). The study aim was to examine the association of 24-hour rest-activity rhythm (RAR) with plasma Amyloid-Tau-Neurodegeneration (ATN) biomarkers and amyloid PET in adults with DS. Methods Cross-sectional study of adults with DS (25–61 years) enrolled in the Alzheimer Biomarker Consortium-Down syndrome who underwent wrist-worn actigraphy, plasma ATN and amyloid PET assessment. Primary variables were measures of 24-hour RAR: interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), L5 (least active 5-hour period) and M10 (most active 10-hour period). Secondary measures included: coefficient of variation of total sleep time, sleep midpoint, and sleep efficiency; and the sleep regularity index (SRI). ATN biomarkers included amyloid beta 42/40 ratio, phosphorylated-tau 181 (pTau181), and neurofilament light chain. Amyloid PET were harmonized using centiloids. Analyses were performed using linear regressions. Covariates included age, sex, intellectual disability level, site, and obstructive sleep apnea severity. Results Of 91 participants, mean (SD) age was 39.5 (8.6) years and 43% were female. After adjustment, higher IV (indicating fragmentation of RAR in a 24-hour period) was associated with increased levels of pTau181 [standardized beta (β)=0.22, p=0.02]. Higher RA (indicating robust RAR) and higher SRI (indicating consistent and regular sleep patterns) were associated with lower pTau181 (β = -0.21, p=0.03 and β = -0.21, p=0.03, respectively). In the subsample of participants who had amyloid PET data available at the time of analysis (n = 50), higher IV was associated with increased centiloids (β=0.22, p=0.04). Conclusion These findings suggest that circadian rhythm disruption (RAR) is associated with plasma and imaging biomarkers of AD. Further research is needed to understand whether interventions to strengthen circadian rhythms reduce AD biomarker burden. Support (if any) This manuscript was supported by NIH grant #T32HL007909 and #F31AG085730. Data was collected as part of the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) and a related Lifestyle R01 study that are funded by the National Institute on Aging and the National Institute for Child Health and Human Development (U01AG051406, U01AG051412, U19AG068054; R01AG070028) and the Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (NIH INCLUDE Project).