# Treadmill Walking Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial

> **NIH NIH R01** · KESSLER FOUNDATION, INC. · 2020 · $378,194

## Abstract

Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with multiple sclerosis
(MS). Exercise training is a promising approach for managing cognitive dysfunction in MS; however, results
from previous randomized controlled trials (RCTs) have been equivocal. This is inconsistent with the well-
established literature from the general population that consistently documents beneficial effects of exercise
training on cognition and brain function. Indeed, the MS RCTs suffer from significant methodological flaws
and are not on par with the rigor of exercise training studies on cognition in the general population. To that
end, we recently completed a line of research that identified progressive (i.e., both intensity and duration)
treadmill walking exercise as an optimal exercise training intervention for improving cognitive processing
speed (CPS; the most commonly impaired cognitive domain in MS) and thalamocortical resting-state
functional connectivity (RSFC), in particular, among fully-ambulatory persons with MS. To that end, the
purpose of the present proposal is to conduct an adequately-powered, single-blind, RCT, using an active
control condition for improving CPS and brain function in cognitively-impaired persons with MS at a single
research site. This study will examine the effects of 3-months of supervised, progressive chronic treadmill
walking exercise (designed based on pilot work) compared with a placebo control condition (i.e., stretching-
and-toning activities) on CPS, fMRI (i.e., thalamocortical RSFC), and functional outcomes in 88 persons with
MS who present with slowed CPS. We will collect data on CPS, thalamocortical RSFC, and functional
outcomes at baseline and follow-up (i.e., at the conclusion of the 3-month intervention period) time points.
We hypothesize that treadmill walking exercise training will result in significant improvements in CPS,
thalamocortical RSFC, and functional outcomes. We further speculate that improvements in thalamocortical
RSFC might explain exercise-related improvements in CPS. If successful, the proposed study will provide
the first Class I evidence for the effects of treadmill walking exercise training as a rehabilitative approach to
improve CPS, its neural correlate, and functional consequences in persons with MS who need such an
intervention the most. This line of research will lay the groundwork for the development of exercise training
guidelines that can be adapted by clinicians for use by MS patients for specifically improving cognition and
brain health. Such an evidence-based approach for rehabilitation, using exercise training, is paramount
considering the prevalent, disabling, and poorly-managed nature of MS-related CPS impairment. This is
consistent with the National Center for Medical Rehabilitation Research’s mission to foster development of
scientific knowledge needed to enhance the health, productivity, independence, and quality of life of persons
with physical disabil...

## Key facts

- **NIH application ID:** 10237433
- **Project number:** 7R01HD091155-03
- **Recipient organization:** KESSLER FOUNDATION, INC.
- **Principal Investigator:** Brian M Sandroff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,194
- **Award type:** 7
- **Project period:** 2018-02-08 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237433

## Citation

> US National Institutes of Health, RePORTER application 10237433, Treadmill Walking Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial (7R01HD091155-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10237433. Licensed CC0.

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