Higher intradaily variability in 24-hour rest-activity rhythm was associated with increased levels of pTau181 (β 0.21, p=0.03) and amyloid PET centiloids (β 0.30, p=0.04) in adults with Down syndrome.
Cross-Sectional (n=93)
Yes
Is circadian rhythm disruption associated with Alzheimer's disease biomarkers in adults with Down syndrome?
Circadian rhythm disruption, measured via 24-hour rest-activity rhythm, is associated with plasma and imaging biomarkers of Alzheimer's disease in adults with Down syndrome.
Effect estimate: β 0.21
p-value: p=0.03
Abstract Rationale Little is known about circadian rhythm disruption and Alzheimer’s disease (AD) biomarkers in adults with Down syndrome (DS). This study tested the hypothesis that there is an association of 24-hour rest-activity rhythm (RAR) with plasma Amyloid-Tau-Neurodegeneration (ATN) biomarkers and amyloid PET scan in adults with DS. Methods Cross-sectional study of adults with DS (25-61 years) enrolled in the Alzheimer Biomarker Consortium-Down syndrome (ABC-DS) who underwent wrist-worn actigraphy, plasma ATN and amyloid PET scan 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). Plasma ATN biomarkers included amyloid beta 42/40 ratio, phosphorylated-tau 181 (pTau181), and neurofilament light chain (NfL). Amyloid PET scans were harmonized using centiloids. Clinical AD status based on a case consensus process determined cognitive status of participants (stable vs mild cognitive impairment MCI vs AD). Analyses were performed using linear and ordinal logistic regressions. Covariates included age, sex, intellectual disability function, site, and obstructive sleep apnea severity. Exploratory analysis was used to evaluate pTau181 and risk of MCI and AD. Results Of 93 participants, mean (SD) age was 39.6 (8.6) years and 41.9% 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: 0.21, p = 0.03). Higher RA (indicating robust RAR) and higher SRI (indicating consistent and regular sleep patterns) were associated with lower pTau181 (β: -0.21, p = 0.02 and β: -0.20, p = 0.03, respectively). In the subsample of participants who had amyloid PET data available at the time of analysis (n = 29), higher IV was associated with increased centiloids (β = 0.30, p = 0.04). In the exploratory analysis, higher pTau181 was associated with increased odds-ratio for MCI and AD (OR: 1.021, 95% CI: 1.004 to 1.038; p = 0.02). Conclusion These findings suggest that circadian rhythm disruption as measured via 24-hour RAR is associated with plasma and imaging biomarkers of AD in DS. Further research is needed to understand whether interventions to strengthen circadian rhythms reduce AD biomarker burden. This abstract is funded by: NIH, NIHR, Windsor Research Unit
Chung et al. (Fri,) conducted a cross-sectional in Down syndrome (n=93). 24-hour rest-activity rhythm (RAR) assessment was evaluated on Association of 24-hour rest-activity rhythm (RAR) with plasma Amyloid-Tau-Neurodegeneration (ATN) biomarkers and amyloid PET scan (β 0.21, p=0.03). Higher intradaily variability in 24-hour rest-activity rhythm was associated with increased levels of pTau181 (β 0.21, p=0.03) and amyloid PET centiloids (β 0.30, p=0.04) in adults with Down syndrome.