Systematically-Developed Pilot Randomized Controlled Trial of Exercise and Cognition in Persons with Multiple Sclerosis

Background: Slowed cognitive processing speed (CPS) is common, debilitating, and difficult to manage in persons with multiple sclerosis (MS). Exercise training represents a promising behavioral approach for managing slowed CPS in MS. This is based on a rigorous and systematic line of research that identified progressive (both intensity and duration) treadmill walking exercise as an optimal exercise stimulus for improving CPS in fully-ambulatory persons with MS.

Objectives: The present pilot study adopted a single-blind randomized controlled trial (RCT) design and is the first to examine the effect of a systematically-developed progressive treadmill walking exercise training intervention on measures of CPS among fully-ambulatory persons with MS.

Methods: 10 fully-ambulatory females with relapsing-remitting MS were randomly assigned into exercise training intervention or waitlist control conditions. The intervention condition involved 3-months of supervised, progressive chronic treadmill walking exercise training that was designed based on pilot work and American College of Sports Medicine guidelines. Participants underwent measures of cardiorespiratory fitness (VO_2peak) and CPS before and after the 3-month period; all baseline and follow-up assessments were performed by blinded assessors.

Results: Overall, there were large intervention effects on VO_2peak (d=1.08) such that persons who underwent the treadmill walking exercise demonstrated a 14% improvement in cardiorespiratory fitness, whereas there was minimal change for those in the control condition. There further were large effects on Symbol Digit Modalities Test (SDMT) performance (d=0.95) such that persons who underwent treadmill walking exercise training demonstrated a 3-point increase in SDMT scores, whereas those who underwent the waitlist control condition demonstrated a 3-point decrease in SDMT scores. Importantly, changes in VO_2peak were significantly associated with changes in SDMT scores (r=.60) such that improved cardiorespiratory fitness was moderately-to-strongly associated with improvements in CPS.

Conclusions: This small pilot RCT provides exciting proof-of-concept data supporting progressive treadmill walking exercise training for potentially improving cardiorespiratory fitness and CPS over time in fully-ambulatory persons with MS, and that improving cardiorespiratory fitness is seemingly a mechanism for improved CPS in this population.