Association of Changes in Activity Patterns With Brain Atrophy and Disability Progression in People With Multiple...

The purpose of this study was to evaluate whether accelerometry detects subtle changes in disability in people with multiple sclerosis (PwMS). Specifically, we tested how accelerometry measures change longitudinally in PwMS and assessed how these changes translate to brain atrophy and disability worsening at the individual level.

We included PwMS aged 40 years or older with approximately annual brain MRI who wore GT9X Actigraph accelerometers every 3 months over 3 years. Accelerometry-derived indices included total and 2-hour specific activity, sedentary time, and circadian rhythm parameters. Confirmed disability worsening was characterized using the composite Expanded Disability Status Scale-plus (EDSS+), and whole-brain segmentation was performed. We modeled within-person and between-person effects using Cox (for EDSS+) and linear mixed-effects (for MRI) multivariable-adjusted models adjusted for age, sex, and body mass index that included only accelerometry measures obtained before EDSS+.

Among 238 PwMS (mean age 54.8, 29% male), 120 experienced EDSS+-confirmed progression over a mean 2.9 years (SD 1.1 years). Participants wore accelerometers an average of 7.4 times over 67 days. Total activity declined an average of 43,737 activity counts (2.0% decline per year; 95% CI -59,812 to -27,663; p = 1.11 × 10^-7). Within-person decreases in daytime activity (particularly 8:00-14:00) were associated with higher risk of EDSS+. For example, a 1-SD decrease in within-person (individual-level) activity from 8:00 to 10:00, 10:00 to 12:00, and 12:00 to 14:00 was associated with a respective 1.20 (95% CI 1.04-1.40), 1.24 (95% CI 1.07-1.43), and 1.23 (95% CI 1.06-1.44) higher risk of confirmed disability progression by EDSS+. MRI models also demonstrated that within-person declines in morning activity (8:00-10:00) were associated with greater whole-brain, deep gray matter, and thalamic volume loss (for whole brain -0.18%; 95% CI -0.31 to -0.06; deep gray -0.34%; 95% CI -0.52 to -0.15; and thalamic -0.35%; 95% CI -0.58 to -0.11). Lower between-person mean moderate-to-vigorous physical activity was associated with lower brain volumes over time but was not associated with EDSS+.

Within-person reductions in daytime activity patterns precede clinical disability worsening and brain atrophy in PwMS. Although results require confirmation and thresholds of and responsiveness to change need to be established, longitudinal accelerometry may offer sensitive, noninvasive biomarkers of subclinical disease.