Exercise Therapy in Early Multiple Sclerosis Improves Physical Function But Not Cognition: Secondary Analyses From a Randomized Controlled Trial

Background: Exercise positively affects multiple sclerosis (MS) symptoms, physiological systems, and potentially cognition. However, an uninvestigated “window of opportunity” exists for exercise therapy early in the disease. Objective: This study presents secondary analyses from the Early Multiple Sclerosis Exercise Study, and aims to investigate the efficacy of exercise on physical function, cognition, and patient-reported measures of disease and fatigue impact early in the disease course of MS. Methods: This randomized controlled trial (n = 84, time since diagnosis <2 years) included 48 weeks of aerobic exercise or an active control condition (health education) and between-group changes are based on repeated measurement mixed regression models. Physical function tests included measures of aerobic fitness, walking (6-minute walk, Timed 25-foot walk, Six-spot step test), and upper-limb dexterity. Tests of processing speed and memory evaluated cognition. The questionnaires Multiple Sclerosis Impact Scale and Modified Fatigue Impact Scale assessed perception of disease and fatigue impact. Results: Following early exercise aerobic fitness showed superior between-group physiological adaptations (4.0 [1.7; 6.3] ml O₂/min/kg; large effect size [ES = 0.90]). No other outcomes showed significant between-group differences, yet all measures of walking and upper-limb function showed small-to-medium effect sizes in favor of exercise (ES = 0.19−0.58). Overall disability status as well as cognition were unaffected by exercise, whereas perception of disease and fatigue impact were reduced in both groups. Conclusion: In early MS, 48 weeks of supervised aerobic exercise seem to positively modify physical function, but not cognitive function. Perception of disease and fatigue impact may be modifiable by exercise in early MS. Trial registration: Clinicaltrials.gov (identifier: NCT03322761).