Effects of Cognitive Rehabilitation on Brain Grey Matter Volume and Go-noGo Activity in Progressive Multiple Sclerosis: Results from the CogEx Study
Maria Rocca1, Paola Valsasina3, Francesco Romano3, Rob Motl4, Maria Amato5, Giampaolo Brichetto6, Daniele Vincenzo Boccia7, Jeremy Chataway8, Nancy Chiaravalloti9, Gary Cutter10, Ulrik Dalgas11, John DeLuca9, Rachel Farrell8, Peter Feys12, Jennifer Freeman13, Matilde Inglese7, Cecilia Meza14, Amber Salter15, Brian Sandroff9, Anthony Feinstein14, Massimo Filippi2
1Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 3Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 4Department of Kinesiology and Nutrition, University of Illinois Chicago, 5Department NEUROFARBA, Section Neurosciences, University of Florence, 6AISM Rehabilitation Service, Italian MS Society, 7Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, 8Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, 9Kessler Foundation, 10Department of Biostatistics, University of Alabama At Birmingham, 11Exercise Biology, Department of Public Health, Aarhus University, 12REVAL, Faculty of Rehabilitation Sciences, Hasselt University, 13Faculty of Health, School of Health Professions, University of Plymouth, 14Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, 15Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center
Objective:
To present volumetric MRI and task-related functional MRI (fMRI) findings of the CogEx study (ClinicalTrials.gov, NCT03679468).
Background:
CogEx was a randomized, sham-controlled trial aimed at determining effectiveness of cognitive rehabilitation (CR) and aerobic exercise (EX), administered alone or combined together, in progressive (P) multiple sclerosis (MS).
Design/Methods:
Participants were randomized (1:1:1:1) 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. Physical/cognitive assessments were performed at baseline, immediately after intervention (week-12) and 6 months post-intervention (month-9). MRI sub-study participants underwent volumetric MRI and fMRI during a sustained attention task (Go-NoGo) at the same time points.
Results:
104 PMS participated in the CogEx MRI sub-study (“CR plus EX”: n=25; “CR plus EX-S”: n=28; “CR-S plus EX”: n=25; “CR-S plus EX-S”: n=26). At week-12 and month-9, no differences were found among interventions for Symbol digit modalities test (SDMT) correct response number, nor for SDMT, California verbal learning test (CVLT) and Brief visuospatial memory test Z-scores (p=range 0.12-0.94). Time-by-treatment interactions for changes at week-12 vs baseline of normalized grey matter (NGMV) (p=0.10) and cortical grey matter (NcGMV) (p=0.10) volumes were not significant. However, they became significant (NGMV: p=0.04; NcGMV: p=0.02) when comparing all patients performing CR (i.e., “CR plus EX” and “CR plus EX-S”) vs all patients performing CR-S. “CR plus EX-S” patients exhibited Go-NoGo-related fMRI activity increase (p<0.05, corrected) at week-12 vs baseline in bilateral insular regions. The same trend (p<0.001, uncorrected) was seen in all patients performing CR. In the same patients, increased NGMV (r=0.42, p=0.004) and NcGMV (r=0.36, p=0.01) at week-12 vs baseline correlated with increased CVLT Z-score. No differences were found for the remaining week-12 and month-9 changes of volumetric and functional MRI metrics.
Conclusions:
CR modulated GM volumes and insular fMRI activity in PMS.