Cardiorespiratory fitness does not predict longitudinal changes in manual dexterity, cognition or corticospinal excitability in multiple sclerosis.

Introduction: Neurodegeneration in multiple sclerosis leads to progressive cognitive and motor impairments. Cardiorespiratory fitness (CRF) is thought to protect against such decline, but its longitudinal effects remain unclear. This study examined whether CRF predicts changes in behavioral (i.e., hand dexterity and cognition) and neurophysiological (i.e., corticospinal excitability, an indicator of corticospinal tract function) outcomes in multiple sclerosis over 2 years, with a focus on participants who experienced no relapses between visits and were, therefore, classified as progression independent of relapse activity (PIRA). We hypothesized that higher baseline CRF would be associated with better follow-up outcomes. Methods: Participants underwent assessments at two time points (∼2 years apart). CRF was measured using a graded maximal exercise test ( Results: Among 38 participants (71% female), CRF at baseline did not significantly predict changes in behavioral or physiological outcomes ( Discussion: CRF did not predict longitudinal changes in manual dexterity, cognition or corticospinal excitability in individuals living with multiple sclerosis. Instead, initial performance was the primary determinant of follow-up outcomes, suggesting that achieving better function at baseline (earlier in the disease) is an important rehabilitation target. Variability in longitudinal change underscores the heterogeneous nature of disease progression/improvement and the need for specific, targeted interventions and personalized strategies to disease management.