Results from the International Multicenter Clinical Trial to Improve Cognition in People with Progressive Multiple Sclerosis (CogEx)

Summary: A large multicenter international clinical trial supported by MS Canada aimed to test whether the interventions, cognitive rehabilitation or aerobic exercise, or both interventions provided together, can improve cognition in people with progressive MS. The results of the clinical trial show that cognitive rehabilitation combined with aerobic exercise was not better than either intervention alone in improving cognition. The researchers did find that two-thirds of all participants in the trial showed an improvement in information processing speed and almost half retained these improvements at 6 months after the intervention, demonstrating that cognition can be improved in people with progressive MS.  


Background: Cognitive dysfunction affects approximately 40-80% of people with MS, with the greatest rates being in those with progressive MS. Impaired cognition affects a person’s ability to work, maintain relationships, and perform daily tasks. There are currently no known treatments for improving cognition in people with progressive MS.

Details: In the CogEx clinical trial, funded by MS Canada, a group of multidisciplinary researchers led by Dr. Anthony Feinstein (University of Toronto / Sunnybrook Health Sciences Centre) aimed to determine  whether the interventions, cognitive rehabilitation or aerobic exercise, or a combination of both, can lead to improvements in cognition in people with progressive MS.

This study was an international multicenter clinical trial that took place at 11 centres across six countries (Belgium, Canada, Denmark, Italy, UK, and USA). A total of 311 participants were assigned to one of four treatment groups (listed below), where they received the following interventions twice per week over a 12-week period*: 

  1. Cognitive rehabilitation plus sham exercise
  2. Aerobic exercise plus sham cognitive task
  3. Cognitive rehabilitation and aerobic exercise (combined intervention)
  4. Sham cognitive task and sham exercise

The study assessed information processing speed as a measure of cognition using the Symbol Digit Modalities Test (SDMT). They measured SDMT at baseline (start of the study), at the end of the intervention at 12 weeks, and then at 6-months after the intervention.

Results: Researchers did not observe significant differences in the processing speed of participants between the four treatment groups. However, two-thirds of all participants, regardless of the type of intervention received, showed significant improvements in processing speed at 12 weeks of intervention compared with baseline. Almost 50% of participants retained these improvements in processing speed at the 6-month follow-up.

Impact: While the study was not able to show that cognitive rehabilitation and aerobic exercise combined were superior to either intervention alone, the findings suggest that improvements in processing speed may be achievable in people with progressive MS. The participants who showed improvements may have benefited from being more active in the trial, pointing to the potential benefits of enhancing one’s intellectual, physical, and social activities that build a resistance to damage in the brain, known as ‘cognitive reserve’.   

*Description of treatments/interventions:

  • Cognitive rehabilitation intervention was individualized, computer-based, incremental approach to improve processing speed (i.e. RehaCom program).
  • Exercise intervention was individualized aerobic training using a recumbent arm–leg stepper.
  • Sham cognitive task consisted of internet training provided individually.
  • Sham exercise consisted of stretching and balance tasks without inducing cardiovascular strain.


Article published in The Lancet Neurology on September 20, 2023 – Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive multiple sclerosis (CogEx): a multi-arm, randomised, blinded, sham-controlled trial. Link to article – here.

Additional Information:

Learn more about the CogEx study – here.

See the press release - here

See exercise guidelines for adults with MS – here.

This study was funded by MS Canada by way of a generous philanthropic investment by the FDC Foundation.