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

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

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.

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