High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial

Mult Scler. 2018 Oct;24(12):1635-1644. doi: 10.1177/1352458517728342. Epub 2017 Aug 21.


Background: Aerobic exercise can improve cognitive performance in healthy elderly people.

Objective: The aim of this study was to investigate the influence of a 3-week high-intensity aerobic exercise programme (high-intensity training group (HIT)) on cognitive performance in persons with multiple sclerosis (MS) compared with a standard exercise programme (control training (CT)).

Methods: A total of 60 persons with MS (Expanded Disability Status Scale (EDSS): 1.0-6.5) were randomized to a HIT group (3×/week for 20 minutes, including five 3-minute exercise intervals at 80% of peak oxygen uptake (VO2-peak)) or a CT group (continuously 5×/week for 30 minutes/session at 65% of VO2-peak). Cognitive performance was assessed using the Brief International Cognitive Assessment for MS at entry ( t0) and discharge ( t1). Furthermore, VO2-peak, brain-derived neurotrophic factor, serotonin and matrix metalloproteinases (MMP)-2 and -9 were measured.

Results: Compared to CT, HIT significantly improved verbal memory. Significant improvements over time in executive functions were found in both groups. Secondary outcomes indicated significant improvements in VO2-peak and a significant reduction in MMP-2 in the HIT group only.

Conclusion: HIT represents a promising strategy to improve verbal memory and physical fitness in persons with MS. Further research is needed to determine the impact of exercise on biomarkers in MS.

Trial registration: ClinicalTrials.gov NCT02571335.

Keywords: Exercise; cognition; multiple sclerosis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain-Derived Neurotrophic Factor / blood
  • Cognition*
  • Exercise Therapy / methods*
  • Female
  • High-Intensity Interval Training / methods*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / rehabilitation*


  • Brain-Derived Neurotrophic Factor
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Associated data

  • ClinicalTrials.gov/NCT02571335