Contemporary Clinical Trials

Available online 5 September 2021, 106563
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Effects of walking exercise training on learning and memory and hippocampal neuroimaging outcomes in MS: A targeted, pilot randomized controlled trial

Author links open overlay panelBrianM.SandroffaGlenn R.WylieaJessica F.BairdbC. DanielleJonesbM. DavidDiggscHelenGenovaaMarcas M.BammandGary R.CuttereJohnDeLucaaRobert W.Motlb


The current pilot study involved a single-blind, randomized controlled trial (RCT) on the effects of treadmill walking exercise training compared with an active control condition on learning and memory (L/M) and hippocampal neuroimaging outcomes in 11 fully-ambulatory persons with multiple sclerosis (MS) who demonstrated impairments in new learning.

The study protocol is registered at NCT03319771 (February 2018). Eleven fully-ambulatory persons with MS-related impairments in new learning were randomly assigned into either 12-weeks of supervised, treadmill walking exercise training or 12-weeks of low-intensity resistive exercise (active control condition). Participants underwent neuropsychological tests of L/M and hippocampal neuroimaging before and after the 12-week study period; outcomes were administered by treatment-blinded assessors.

There were moderate-to-large intervention effects on measures of verbal L/M (ηp2 = 0.11, d = 0.63, 95% CI: −0.61, 1.83), whereby those in the intervention condition demonstrated improvement in California Verbal Learning Test-II (CVLT-II) scores compared with the control condition. There were smaller effects on a composite L/M measure (ηp2 = 0.02, d = 0.28, 95% CI: −0.93, 1.46). There were large intervention effects on normalized hippocampal volume (ηp2 = 0.36, d = 1.13, 95% CI: 0.09, 2.82), whereby hippocampal volume was preserved in the intervention condition, compared with hippocampal atrophy in the control condition. By comparison, there were no intervention effects on hippocampal resting-state functional connectivity.

Collectively, this study provides initial proof-of-concept data for further examining treadmill walking exercise training as a possible behavioral approach for managing L/M impairment and preserving hippocampal volume as common and debilitating manifestations of MS.