Physical Activity, Vascular Function, and Brain Health in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS) that is associated with impairments in cognitive processing speed (CPS). The impairments in CPS are poorly managed through medication or rehabilitation in MS, yet present considerable burden for persons with MS. There is recent evidence of vascular dysfunction in MS, and this have been associated with worse CPS in MS. Physical activity is associated with better vascular function and CPS in MS, but the possible mechanism has been incompletely described and characterized. Cerebral pulsatility index measured in the middle cerebral artery may reflect consequences of vascular dysfunction in large arterial and cerebral microvascular segments, however in closer proximity to the brain than previously measured metrics of vascular dysfunction in MS such as aortic stiffness. There are further data of elevated serum neurofilament light (sNfL) levels in MS, and sNfL has been associated with cognitive and cerebrovascular endpoints in MS. Collectively, this study compares and examines hypothesized associations among physical activity, measured by body-worn accelerometry, brain vascular function, as measured by cerebral pulsatility index, cognitive function, measured by CPS, and CNS neuronal integrity, measured with sNfL, in persons with MS compared with controls matched for age, sex, and body mass index. The study will further examine cerebral pulsatility index as a mediator of the associations among physical activity, sNfL, and cognition in MS. We hypothesize that people with MS will have lower levels of physical activity, higher levels of sNfL, and lower CPS compared with controls. Additionally, we hypothesize that higher physical activity will be associated with lower cerebral pulsatility index, lower levels of sNfL, and higher CPS. We further hypothesize that the relationships between physical activity and both sNfL and CPS will be indirect and accounted for by cerebral pulsatility index, and this indirect, mediation association may be stronger in MS. This study will provide the groundwork for developing a randomized controlled trial that changes PA behavior for preserving brain vascular function, neuronal integrity, and cognition in people with MS. Project Number: 1F31HD117697-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Noah Dubose | Institution: UNIVERSITY OF ILLINOIS AT CHICAGO, Chicago, IL | Award Amount: $47,003 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F01A-S (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1F31HD11769701A1