Cognitively stimulating activities in multiple sclerosis: Results of a randomized controlled trial

Abstract Background Cognitively stimulating activities (CSAs) are associated with cognitive reserve in people with multiple sclerosis (pwMS). Objective To investigate the effect of 12 weeks of increased CSA engagement on objective and subjective cognition. Methods Using computer-generated allocation tables, sixty non-depressed pwMS were randomized (1:1), stratified by disease course, to a 12-week CSA intervention or passive control. The main inclusion criteria were age 18–65, an Expanded Disability Status Scale score ≤ 6.5, and cognitive impairment. Co-primary endpoints were mean change scores from baseline to 12-week follow-up on the oral Symbol Digit Modalities Test (SDMT) and the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ). These were assessed using Analysis of Covariance, adjusting for group, baseline score, and education. The trial was registered at Clinicaltrials.org (NCT05691192) Results There was no significant between-group difference in SDMT change scores (β = 2.35, 95% CI [-1.14, 5.85], p = 0.18). There was a significant difference in MSNQ change scores driven by worsening in the control group (β = -4.38, 95% CI [-7.58, -1.17], p = 0.0084). Conclusion The intervention was not associated with improvements in objective cognition. Although a difference was observed for subjective cognition, this was driven by worsening in the control group.