Improving cognition in people with progressive multiple sclerosis

Study summary
Cognitive rehabilitation is designed to enhance a person’s capacity to process and interpret information and improve his/her ability to function in all aspects of family and community life. 
Given the clear and consistent documentation of cognitive deficits in persons with Multiple Sclerosis (MS), there is an obvious need for effective cognitive rehabilitation, particularly in the progressive forms of MS.

While the focus on designing and testing cognitive rehabilitation programmes for persons with MS is relatively recent, the growth in research addressing this need over the past decade has been substantial. Cognitive Rehabilitation studies in MS have focused on various aspects of cognition including attention, working memory, communication skills, and memory functioning.

One promising rehabilitation intervention that may improve cognition (as well as functional physical capacity) is exercise. Exercise training is defined as a subset of physical activity that is planned, structured, and repetitive and has, as a final or an intermediate objective, the improvement or maintenance of physical fitness. For years patients with MS were advised not to participate in physical exercise because it was thought to lead to fatigue or symptom exacerbation in general. Research over the past few decades has changed this view and physical exercise in MS has instead been shown to have a number of beneficial effects.

Primary aims:
1. To determine whether cognitive rehabilitation and exercise are effective treatments for cognitive dysfunction in people with progressive MS.
2. To assess whether cognitive rehabilitation and exercise in combination have synergistic effects in the treatment of cognitive dysfunction in people with progressive MS.

Secondary aims:
1. To assess the everyday life impact of cognitive changes after the different rehabilitation interventions. 
2. To assess brain functional and structural substrates of cognitive changes after the different rehabilitation interventions. 
3. To explore whether heat sensitivity impacts on exercise performance of people with MS.

The CogEx study recruited 311 people with progressive MS across 11 sites worldwide. Participants experienced mild to moderate cognitive difficulties and had an EDSS score between 3.0 – 6.5. There were two sites in the UK: Plymouth and London. 

Participants are screened against eligibility criteria over the phone and through an in-person assessment. Baseline data is collected and the participant then randomised into one of four treatment intervention groups. Once recruited, the cognitive rehabilitation and exercise training consists of twice weekly sessions for a total of 12 weeks

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P. Preziosa, M. A. Rocca, E. Pagani, P. Valsasina, M. P. Amato, G. Brichetto, et al. Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis. J Neurol 2023; 270 (3): 1543-1563 DOI: 10.1007/s00415-022-11486-0

A. Feinstein, M. P. Amato, G. Brichetto, J. Chataway, N. D. Chiaravalloti, G. Cutter, et al. The late onset of emotional distress in people with progressive multiple sclerosis during the Covid-19 pandemic: longitudinal findings from the CogEx study. J Neurol 2022; 269 (12): 6202-6210. DOI: 10.1007/s00415-022-11295-5

Chiravallotti N, De Luca J, Salter A, Pia Amato M, Brichetto G et al. The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis. Multiple Sclerosis Journal 2022 https://journals.sagepub.com/doi/10.1177/13524585221088190

Sandroff BM, Motl RW, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, et al. Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study. Multiple Sclerosis Journal. 2021

Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, et al. The impact of the COVID-19 pandemic on an international rehabilitation study in MS: the CogEx experience. Journal of Neurology. 2021.

Chiaravalloti ND, Amato MP, Brichetto G, Chataway J, Dalgas U, DeLuca J, et al. The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis. Journal of neurology. 2021;268(5):1598-607.

Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti N, Dalgas U, et al. Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx). BMC Neurol. 2020;20(1):204.