Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: Project EXACT

Kessler Foundation43 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Multiple Sclerosis Cognitive Impairment

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Cognitive Processing Speed

Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed)

Time frame: Baseline, Follow-up (up to 14 weeks)

Thalamocortical Resting-State Functional Connectivity Region 1

Change in functional connectivity between the thalamus and left superior medial gyrus based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity.

Time frame: Follow-up at 12-weeks minus baseline

Change in Thalamocortical Resting State Functional Connectivity Region 2

Resting-state functional connectivity between the thalamus and left putamen based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity.

Time frame: Follow-up at 12-weeks minus baseline

Secondary Outcomes

3-second Paced Auditory Serial Addition Test (PASAT)

The 3-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The total score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition