improving cognition in people with progressive multiple sclerosis using aerobic exercise and cognitive rehabilitation

Conditions: Multiple Sclerosis, Primary Progressive; Cognitive Impairment

Summary: given that up to 70% of people with secondary progressive ms are cognitively impaired, the search for effective treatments is considered a priority by people living with the disease. this proposal will address the effectiveness of cognitive rehabilitation (cr) and exercise, either alone, or in combination in this regard. a team of ms researchers has been assembled from the usa, canada, the united kingdom, italy, denmark, germany and belgium for this. a total of 360 people with progressive ms will make up the sample. brain mris will be undertaken in a third of the sample before and after the 12 weeks of treatment to document the functional changes that are expected to occur with symptom improvement.

aim: the broad aim of this proposal is to evaluate a multidisciplinary and multi-modal approach to rehabilitation in people with progressive ms. cognitive rehabilitation and aerobic exercise will be evaluated individually and in combinations to address cognitive dysfunction as the primary outcome variable. over 20 years have passed since the introduction of the first disease modifying treatment, interferon beta-1betaseron (b), for multiple sclerosis (ms).since then 13 treatments have been approved and made it onto the market. all are for relapsing-remitting disease (rrms), apart from mitoxantrone which is limited to progressive disease with relapses, interferon-beta-1b, which is for secondary progressive disease (spms), but does not delay disability progression and ocrelizumab for primary progressive ms only. thus, for a sizeable proportion of people with ms there is no therapeutic option to slow progression. this raises the question, how are patients with primary and secondary progressive ms (ppms and spms) to be helped? while research is underway to find a medication that holds promise of halting further deterioration in a disease that has already entered a progressive stage, patients and their clinicians are left with basically symptomatic treatments. hypothesis: the investigators hypothesize that cr and aerobic exercise are effective treatments for cognitive impairment (processing speed deficits) in people with progressive ms. in particular a combination of these two treatment given twice weekly over 12 weeks is more effective than each individual treatment given alone or as sham. the investigators further hypothesize that improvements in processing speed will be matched on functional mri (fmri) by enhanced neural activity in networks associated with information processing speed.

Eligibility criteria:
inclusion criteria: * have a confirmed diagnosis of progressive multiple sclerosis * visual acuity of 20/70 * language comprehension, to ensure subjects have the ability to understand instructions exclusion criteria: * wheelchair dependent (edss \> 7.0) * history of central nervous system disease other than progressive ms * steroids use within the past 3 months * regular aerobic training (eg. bi-cycling, running, swimming or rowing) * unwilling to travel to study sites for rehabilitation 2 times a week for 3 months