Exercise Training Effects on Cognition and Brain Function in Multiple
Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial
What it found
The main measure showed a statistically significant benefit.
| Measure | Estimate | 95% CI | p |
|---|---|---|---|
| Thalamocortical Resting-State Functional Connectivity Region 1 | .01 | ||
| Change in Thalamocortical Resting State Functional Connectivity Region 2 | .02 | ||
| Cognitive Processing Speed | .34 |
Statistical analysis as posted on ClinicalTrials.gov.
What was tested
Treatment tested
- Treadmill Walking Exercise Training
Compared with
- Stretching-and-Toning Exercise Training
Results by group
Cognitive Processing Speed
Baseline, Follow-up (up to 14 weeks)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Treadmill Walking Exercise Training | 43.5 Raw Score | 9.6 (Standard Deviation) | 13 |
| Stretching-and-Toning Exercise Training | 43.7 Raw Score | 9.2 (Standard Deviation) | 15 |
| Treadmill Walking Exercise Training | 46.5 Raw Score | 12.1 (Standard Deviation) | 13 |
| Stretching-and-Toning Exercise Training | 49.1 Raw Score | 10.7 (Standard Deviation) | 15 |
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
p = .34
Thalamocortical Resting-State Functional Connectivity Region 1
Follow-up at 12-weeks minus baseline
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Treadmill Walking Exercise Training | .0334 z-score | 0.0531 (Standard Deviation) | 11 |
| Stretching-and-Toning Exercise Training | -.0247 z-score | 0.0605 (Standard Deviation) | 14 |
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
p = .01
Change in Thalamocortical Resting State Functional Connectivity Region 2
Follow-up at 12-weeks minus baseline
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Treadmill Walking Exercise Training | .0193 z-score | 0.0595 (Standard Deviation) | 11 |
| Stretching-and-Toning Exercise Training | -.0414 z-score | 0.0783 (Standard Deviation) | 14 |
Treadmill Walking Exercise Training
Stretching-and-Toning Exercise Training
p = .02
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Treadmill Walking Exercise Training | 19 | 0 (0.0%) | 0 |
| Stretching-and-Toning Exercise Training | 20 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Cognitive Processing Speed
Baseline, Follow-up (up to 14 weeks)
Thinking and memoryThalamocortical Resting-State Functional Connectivity Region 1
Follow-up at 12-weeks minus baseline
Nerve conduction testsChange in Thalamocortical Resting State Functional Connectivity Region 2
Follow-up at 12-weeks minus baseline
Nerve conduction tests
Other measures (7)
3-second Paced Auditory Serial Addition Test (PASAT)
Baseline, Follow-up (up to 14-weeks)
Thinking and memory2-second Paced Auditory Serial Addition Test (PASAT)
Baseline, Follow-up (up to 14-weeks)
Thinking and memoryPattern Comparison Test
Baseline, Follow-up (up to 14-weeks)
Thinking and memoryCommunity Integration Questionnaire
Baseline, Follow-up (up to 14-weeks)
Quality of life (reported by participants)Lawton-Brody Instrumental Activities of Daily Living
Baseline, Follow-up (up to 14-weeks)
Quality of life (reported by participants)Multiple Sclerosis Impact Scale-29 Physical Subscale
Baseline, Follow-up (up to 14-weeks)
Quality of life (reported by participants)Timed 25-foot Walk
Baseline, Follow-up (up to 14-weeks)
Disability progressionWalking and mobility
Who could take part
MS (type not specified) · 18 to 65 · EDSS 0 to 4.0
Show the full criteria
Inclusion criteria
All participants will: * Be between the ages of 18-65 * Have a clinically definite MS diagnosis based on established criteria * Be fully-ambulatory based on Expanded Disability Status Scale (EDSS) scores between 0-4.0 * Demonstrate slowed CPS based on initial SDMT scores at least 1 SD below the regression-based normative score for healthy controls (i.e., 16th percentile) * Be relapse-free and will not have acutely taken corticosteroids for at least 30 days (i.e., relative neurologic stability) * Not have a history of major depressive disorder, schizophrenia, bipolar disorder I or II, or substance-abuse disorders. * Not be taking medications that can affect cognition (e.g., antipsychotics, benzodiazepines). * Be right-handed * Have corrected vision better than 20/80 * Not have known/diagnosed cardiovascular, metabolic, or renal disease. Individuals with known/diagnosed cardiovascular, metabolic, or renal disease who are asymptomatic will be included only with a physician's approval. * Demonstrate scores on the Mini-Mental State Examination (MMSE) of 21 or higher (no decisional impairment) * Be on a stable disease-modifying therapy regimen (i.e., at least 6 months prior to study enrollment). * Have a low risk for contraindications for MRI based on not having metal (e.g., non-MRI compatible aneurysm clips, metal shards in the body or eyes, or recently placed surgical hardware) or electronic devices (e.g., pacemaker, cochlear implant) within the body. * Not be pregnant * Not be engaging in ≥ 150 min of moderate-to-vigorous physical activity (i.e., not meeting public health guidelines for physical activity) per week * Not be actively engaging in cognitive rehabilitation, or participating in regular brain fitness activities * Demonstrate systolic blood pressure values of \< 200 mmHg or diastolic blood pressure values \< 110 mmHg at rest
Exclusion criteria
Not separately supplied in the registry.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with MS and exercise training might represent a promising approach to manage this symptom of the disease. The proposed study aims to examine the effects of 3-months of supervised, progressive (both intensity and duration) treadmill walking exercise training (designed based on pilot work and American College of Sports Medicine guidelines) compared with an active control condition (i.e., stretching-and-toning activities) on cognitive processing speed and functional MRI outcomes in 88 cognitively-impaired persons with MS. This study is critical for providing evidence supporting treadmill walking exercise training as a behavioral approach for managing slowed cognitive processing speed (i.e., the most common MS-related cognitive impairment) and improving brain health in persons with MS.
Papers
Results
Safety, adherence, and compliance in a RCT of supervised exercise training among persons with multiple sclerosis who have slowed cognitive processing speed.Mult Scler Relat Disord · 2025
Results
Aerobic walking exercise training boosts thalamic connectivity in MS patients with cognitive processing speed impairment.Brain Cogn · 2025
Loading reviews and guidelines…
History
Started
Feb 2019
Main results due
Dec 2023
Finished
Dec 2024
Results posted
Jun 2025