Rest-activity and circadian rhythm parameters relate to cognition and disability outcomes in multiple sclerosis
- 1Columbia Multiple Sclerosis Center, Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center
Abstract
OBJECTIVETo prioritize novel measures of disease progression, we examined whether actigraphy-derived rest-activity rhythm (RAR) parameters relate to cognitive performance as well as disability in a multiple sclerosis (MS) cohort enrolled in a prospective brain donation program.
METHODSRAR parameters were assessed using a wrist actigraphy device (AX3 Axivity Actiwatch, Axivity Ltd.) over two weeks. The primary outcome measure was the Symbol Digit Modalities Test (SDMT, N=222). Secondary outcomes included Brixton Spatial Anticipation Test and self-reported disability. In 76 participants, volumetric measures were derived from repurposed clinical magnetic resonance imaging (MRI) data. We applied linear and logistic regression models, adjusting for age, sex, education, time since MS diagnosis, and body mass index.
RESULTSAfter correction for multiple comparisons, higher intradaily variability (IV) of RAR and lower relative amplitude were associated with worse SDMT performance; higher IV was also associated with greater odds of disability. A broader set of RAR parameters was associated with disability measure. No MRI parameters were related to RAR in the subset of individuals with available MRI data, although we note suggestive associations with hippocampal and choroid plexus volumes warranting further investigation.
INTERPRETATIONMore robust circadian rhythms were related to better cognition. These results highlight the utility of actigraphy and its more nuanced measures beyond the simple summaries of activity levels that quantitate the extent of motor disability. Selected RAR features may be an effective non-invasive approach to capture clinically relevant quantitative measures of brain function for persons with MS.
Related
- Diet and physical activity in multiple sclerosis: associations with quality of life and disability by disease duration.
- Functional disability and cognition in relation to residential transitions in older adults: Evidence from three French cohorts, 1988-2018
- Hormone Replacement Therapy and Disability Progression in Women with Multiple Sclerosis
- Apathy-depression overlap: unmasking hidden disability profiles in multiple sclerosis
- Predicting follow-up cognition using estimated structural and functional connectivity networks and artificial intelligence in multiple sclerosis
BibTeX
@misc{wolfova2026restactivity,
title = {{Rest-activity and circadian rhythm parameters relate to cognition and disability outcomes in multiple sclerosis}},
author = {K. Wolfova and C. White and N. Montazeri Ghahjaverestan and T. Choeying and R. Arevalo and K. Onomichi and L. Davis and V. M. Leavitt and K. Buyukturkoglu and C. Riley and A. Lim and P. De Jager},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.26361636},
url = {https://www.medrxiv.org/content/10.64898/2026.08.31.26361636v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Rest-activity and circadian rhythm parameters relate to cognition and disability outcomes in multiple sclerosis
AU - K. Wolfova
AU - C. White
AU - N. Montazeri Ghahjaverestan
AU - T. Choeying
AU - R. Arevalo
AU - K. Onomichi
AU - L. Davis
AU - V. M. Leavitt
AU - K. Buyukturkoglu
AU - C. Riley
AU - A. Lim
AU - P. De Jager
PY - 2026
DA - 2026/08/31
PB - medRxiv
DO - 10.64898/2026.08.31.26361636
UR - https://www.medrxiv.org/content/10.64898/2026.08.31.26361636v1
AB - OBJECTIVETo prioritize novel measures of disease progression, we examined whether actigraphy-derived rest-activity rhythm (RAR) parameters relate to cognitive performance as well as disability in a multiple sclerosis (MS) cohort enrolled in a prospective brain donation program. METHODSRAR parameters were assessed using a wrist actigraphy device (AX3 Axivity Actiwatch, Axivity Ltd.) over two weeks. The primary outcome measure was the Symbol Digit Modalities Test (SDMT, N=222). Secondary outcomes included Brixton Spatial Anticipation Test and self-reported disability. In 76 participants, volumetric measures were derived from repurposed clinical magnetic resonance imaging (MRI) data. We applied linear and logistic regression models, adjusting for age, sex, education, time since MS diagnosis, and body mass index. RESULTSAfter correction for multiple comparisons, higher intradaily variability (IV) of RAR and lower relative amplitude were associated with worse SDMT performance; higher IV was also associated with greater odds of disability. A broader set of RAR parameters was associated with disability measure. No MRI parameters were related to RAR in the subset of individuals with available MRI data, although we note suggestive associations with hippocampal and choroid plexus volumes warranting further investigation. INTERPRETATIONMore robust circadian rhythms were related to better cognition. These results highlight the utility of actigraphy and its more nuanced measures beyond the simple summaries of activity levels that quantitate the extent of motor disability. Selected RAR features may be an effective non-invasive approach to capture clinically relevant quantitative measures of brain function for persons with MS.
ER -