Physical activity, vascular function, and brain health in multiple sclerosis

The National Institute of Child Health and Human Development awarded the University of Illinois $141,585 on January 29, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct a research study examining associations among physical activity, brain vascular function, cognitive processing speed, and central nervous system neuronal integrity in persons with multiple sclerosis compared with age-, sex-, and body mass index-matched controls.

The study measures physical activity via body-worn accelerometry, brain vascular function via cerebral pulsatility index in the middle cerebral artery, cognitive processing speed via standardized testing, and central nervous system neuronal integrity via serum neurofilament light levels. The research tests the hypothesis that higher physical activity correlates with lower cerebral pulsatility index, lower serum neurofilament light levels, and higher cognitive processing speed in multiple sclerosis populations, and examines cerebral pulsatility index as a mediator of associations among physical activity, neuronal integrity markers, and cognition.

The award is classified as a Project Grant, an assistance type. Performance occurs in Chicago, Illinois, with a period of performance through August 16, 2027.

Abstract

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.