• J. Neurol. Neurosurg. Psychiatr. · Nov 2024

    Randomized Controlled Trial Multicenter Study

    Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

    • Maria A Rocca, Paola Valsasina, Francesco Romanò, Nicolò Tedone, Maria Pia Amato, Giampaolo Brichetto, Vincenzo Daniele Boccia, Jeremy Chataway, Nancy D Chiaravalloti, Gary Cutter, Ulrik Dalgas, John DeLuca, Rachel A Farrell, Peter Feys, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Robert W Motl, Amber Salter, Brian M Sandroff, Anthony Feinstein, Massimo Filippi, and Cogex Research Team.
    • Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy rocca.mara@hsr.it.
    • J. Neurol. Neurosurg. Psychiatr. 2024 Nov 18; 95 (12): 113911491139-1149.

    BackgroundResearch on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.MethodsParticipants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task).Results104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula.ConclusionsIn PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements.Trial Registration NumberNCT03679468.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

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