Association of 24-hour activity patterns with risk of Alzheimer's disease, Parkinson's disease, and cognitive decline

Sleep-wake regulating circuits are affected during prodromal stages in the pathological progression of both Alzheimers disease (AD) and Parkinsons disease (PD). Assessment of 24-hour rhythm impairment may serve as an early indicator of disease and cognitive decline. Our objective was to determine whether objective markers of 24-hour activity are associated with subsequent development of AD, PD, and cognitive decline. This longitudinal study obtained UK Biobank data from 82,829 individuals with valid accelerometer data (collected from June 2013 to January 2016) out of 103,671 eligible adults aged 40 to 79 years with a mean ({+/-}SD) follow-up of 6.8 ({+/-}0.9) years. AD and PD diagnoses were ascertained through September 2021, with data analysis conducted March to November 2022. The outcomes were accelerometer-derived measures of 24-hour activity (derived by cosinor, nonparametric, and functional principal component methods), incident AD and PD diagnosis (obtained through hospitalization or primary care records), longitudinal tests of cognitive function, and demographic characteristics. 82,829 participants consisted of 46,683 women (56%) and 36,146 men (44%) with a mean ({+/-}SD) age of 62.0 ({+/-}7.8) years at the time of actigraphy data collection. During the follow-up period, 191 individuals converted to AD (0.2%) and 266 to PD (0.3%). After adjusting for covariates, interdaily stability, a measure of regularity, (hazard ratio [HR] per SD increase 1.24, 95% confidence interval [CI] 1.04-1.47), diurnal amplitude (HR 0.77, CI 0.64-0.93), mesor (mean activity; HR 0.73, CI 0.56-0.95), and activity during most active 10 hours (HR 0.73, CI 0.59-0.91), were each associated with an increased risk of AD. Diurnal amplitude (HR 0.28, CI 0.23-0.34), mesor (HR 0.12, CI 0.10-0.16), activity during least active 5 hours (HR 0.24, CI 0.08-0.68), and activity during most active 10 hours (HR 0.20, CI 0.16-0.25), were associated with an increased risk of PD. Several measures were additionally predictive of longitudinal cognitive test performance. In this community-based longitudinal study, objective measures of 24-hour activity were associated with elevated risk of AD, PD, and accelerated cognitive decline, suggesting actigraphy-estimated 24-hour rhythm integrity may serve as a scalable early marker of neurodegenerative disease.