Accelerometry-derived activity fragmentation as a predictor of brain atrophy and disability progression in multiple sclerosis

Abstract

Background:

Accelerometry-derived activity fragmentation reflects how frequently active periods are interrupted by sedentary periods. It has been associated with frailty, mortality, and fatigability in the general population; however, its prognostic significance in multiple sclerosis (MS) remains unknown.

Objectives:

To examine whether activity fragmentation is associated with disability progression and brain atrophy in MS.

Methods:

People with MS (PwMS) wore wrist tri-axial accelerometers at 3-month intervals, underwent disability assessments biannually, and underwent magnetic resonance imaging (MRI) brain approximately annually. We evaluated whether active-to-sedentary transition probability (ASTP) during the 10 most active hours of each 24-hour period (M10) was associated with outcomes, by modeling between- and within-person effects.

Results:

Among 238 PwMS, 120 had confirmed Expanded Disability Status Scale (EDSS)-plus progression over a mean of 2.9 ± 1.1 years. Within-person increase in ASTP slope during M10 (indicating increasing activity fragmentation throughout M10) was associated with higher risk of subsequent EDSS-plus progression (per 1 standard deviation (SD) increase: hazard ratio (HR) = 1.21 [95% confidence interval (CI):1.00, 1.45], p = 0.05) and lower deep gray matter and thalamic volumes over time (per 1 SD increase: −0.34 [95% CI: −0.56, −0.12], p = 0.003; −0.40 [95% CI: −0.67, −0.13], p = 0.004, respectively).

Conclusion:

Within-person worsening in activity fragmentation was associated with higher risk of neurologic decline. Activity fragmentation may represent an early compensatory strategy for reduced physiologic reserve and serve as an early indicator of MS progression.