High levels of psychological stress have been reported by 90% of patients with MS experiencing disease exacerbation, and approximately 39% of those with more stable disease course. These stress levels are comparable to patients with a clinical diagnosis of major depression. Cognitive dysfunction affects approximately 40% of community surveyed MS patients, and stress may exacerbate the cognitive burden. Studies have shown that Cognitive Behavior Therapy (CBT) is effective in treating psychological stress. Studies have also shown that exercise is beneficial to mood and cognitive function. Therefore the proposed study will test the comparative benefits of combining CBT and Exercise as an intervention for stress and cognitive dysfunction in MS subjects. The 2 active treatment conditions will be compared with a waitlist control condition.

There are 4 broad aims to this study: 1) to compare the relative efficacy of CBT, Exercise, and CBT-Exercise for stress in MS, 2) to examine the extent to which neuropsychological features of stress and MS, especially working memory and executive functioning, improve following treatments, 3) to determine the extent to which neuropsychological factors are associated with successful treatment response and improved quality of life, and 4) to determine if combined CBT-Exercise confers greater benefits on measures of stress and neuropsychological functioning compared with Exercise alone.

The study hypotheses are: 1) All active treatment conditions will lead to significantly greater improvement on measures of stress at post-treatment and follow-up compared to waitlist controls, 2) Combined CBT-Exercise will lead to comparatively greater symptom reduction compared to all other conditions at post-treatment and follow-up assessments on measures of stress, 3) All active treatment conditions will lead to significant improvement in neuropsychological functioning (particularly measures of working memory and executive functioning) at post-treatment compared to controls, and 4) Combined CBT-Exercise will lead to greater improvement in neuropsychological functioning compared to all other conditions at post-treatment.

The study design allows for examination of the potential additive benefits of CBT and Exercise to usual therapy for patients, and its feasibility as a viable treatment model for MS outpatient clinics and community-based intervention programs. This study will shed light on the treatment of sub-threshold symptoms that are strikingly common in MS population, but often overlooked in favour of more concrete diagnoses (e.g. major depression disorder). This proposed study will also be the first to determine whether evidence-based non-medical treatments for stress and mood disturbances in MS reduce underlying cognitive substrates associated with the illness and known to be exacerbated by stress.

Inclusion Criteria:

• Diagnosis of relapse-remitting MS according to the McDonald criteria
• General Health Questionnaire short form (GHQ-12) score of ≥2
• Extended Disability Status Scale (EDSS) score of ≤5
• Physical Activity Readiness Questionnaire (PAR-Q) score of ≤1

Exclusion Criteria:

• Any past history of traumatic brain injury, psychotic mental illness, developmental delay, substance abuse (excluding cannabis) and systemic illness
• Current (last 6 months) participation in an exercise regimen of moderate-strenuous intensity, greater than 2 days a week
• Incapable of providing informed consent