Correlates of Processing Speed Change With Combined Cognitive Rehabilitation and Exercise in Progressive MS: Secondary Analysis of the CogEx Trial.

Massimo Filippi, Roberto S Hernandez, Gary R Cutter, John DeLuca, Robert W Motl, Brian M Sandroff, Amber Salter, Giampaolo Brichetto, Cecilia Meza, Matilde Inglese, Jennifer Freeman, Peter Feys, Rachel Farrell, Ulrik Dalgas, Nancy D Chiaravalloti, Jeremy Chataway, Maria Pia Amato, Anthony Feinstein, Maria A Rocca

Journal: Neurorehabilitation and neural repair 2025;39(7):499-514

PMID: 40319368

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Abstract

BackgroundCognitive rehabilitation and exercise training are promising approaches for improving cognition in persons with progressive multiple sclerosis (MS). Identifying heterogeneity of change and factors that influence the effects of cognitive rehabilitation and/or exercise training on cognitive outcomes at the individual level have direct relevance for developing tailored and optimized rehabilitation interventions for improving cognition in progressive MS.ObjectiveThis study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity of change in cognitive processing speed (CPS) across the intervention conditions and then identified possible adherence/compliance, baseline performance, and demographic/clinical variables as correlates of rehabilitation-related CPS changes.MethodsA total of 311 persons with progressive MS who were pre-screened for impaired CPS completed 12 weeks of combined cognitive rehabilitation (or sham) and exercise training (or sham). CPS was measured before and after the 12-week period. As potential correlates of CPS changes, we measured adherence/compliance (ie, treatment exposure), performance outcomes at baseline, as well as demographic and clinical characteristics at baseline.ResultsThere was heterogeneity of change in CPS across the 4 intervention conditions. We further identified baseline learning and memory impairment and premorbid intelligence quotient (IQ), but not adherence/compliance, other baseline performance outcomes, or demographic/clinical characteristics as significant correlates of CPS changes across the 4 intervention conditions.ConclusionsThe overall pattern of results suggests that future trials in this area might account for impaired learning and memory and/or premorbid IQ as potential covariates, or more carefully consider the role of reserve within rehabilitation interventions in progressive MS.

Address: Kessler Foundation, West Orange, NJ, USA.; Department of Physical Medicine & Rehabilitation, Rutgers NJ Medical School, Newark, NJ, USA.; Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA.; Department of Neurology, Section on Statistical Planning and Analysis, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy.; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.; Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.; AISM Rehabilitation Service, Italian Multiple Sclerosis Society, Genoa, Italy.; Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.; National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK.; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.; Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.; Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.; REVAL, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.; Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.; Faculty of Health, University of Plymouth, Plymouth, Devon, UK.; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.; IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

DOI: 10.1177/15459683251331586

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MeSH Terms: Humans, Male, Female, Exercise Therapy, Multiple Sclerosis, Chronic Progressive, Middle Aged, Cognitive Dysfunction, Adult, Patient Compliance, Outcome Assessment, Health Care, Aged, Combined Modality Therapy, Cognitive Remediation, Processing Speed, Cognitive Training