Abstract Details

Title Effects of Cognitive Rehabilitation on Brain Grey Matter Volume and Go-noGo Activity in Progressive Multiple Sclerosis: Results from the CogEx Study

Topic Multiple Sclerosis

Presentation(s) S42 - Multiple Sclerosis: Biomarkers/Neuroimaging (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

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).

Objective To present volumetric MRI and task-related functional MRI (fMRI) findings of the CogEx study (ClinicalTrials.gov, NCT03679468).

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.

Authors/Disclosures
Maria A. Rocca (Neuroimaging Research Unit) PRESENTER	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Paola Valsasina	No disclosure on file
Francesco Romano (San Raffaele Hospital)	No disclosure on file
Rob Motl (UIC)	No disclosure on file
Maria P. Amato, PhD (Ospedale Di Careggi)	Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOU Careggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene BMS. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche.
Giampaolo Brichetto, MD, PhD (Italian MS Society)	Giampaolo Brichetto, MD, PhD has received personal compensation for serving as an employee of Italian MS Society.
Vincenzo Daniele Boccia	No disclosure on file
Jeremy S. Chataway, MD	Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janseen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NerveGen. Dr. Chataway has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis.
Nancy Chiaravalloti	No disclosure on file
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, Medimmune/Viela Bio, Medday, Merck/Serono, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, TG Therapeutics.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics,Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc.. Dr. Cutter has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Ulrik Dalgas	Ulrik Dalgas has received personal compensation for serving as an employee of Roche. Ulrik Dalgas has received personal compensation for serving as an employee of Bristol Meyers Squibb.
John DeLuca, PhD, ABPP (Kessler Foundation)	Dr. DeLuca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. DeLuca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. DeLuca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. DeLuca has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. DeLuca has received research support from Biogen.
Rachel A. Farrell, MD (National Hospital for Neurology and Neurosurgery)	The institution of Dr. Farrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma / Jazz. The institution of Dr. Farrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz.
Peter Feys	No disclosure on file
Jennifer Freeman	No disclosure on file
Matilde Inglese, MD, PhD (University of Genoa)	Dr. Inglese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI GENZYME. Dr. Inglese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOGEN. Dr. Inglese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NOVARTIS. Dr. Inglese has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for MERCK-SERONO. Dr. Inglese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE. Dr. Inglese has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MS Journal.
Cecilia Meza (Sunnybrook Research Institute)	No disclosure on file
Amber Salter, PhD (UT Southwestern Medical Center)	Dr. Salter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gryphon Bio. Dr. Salter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abata Therapeutics. Dr. Salter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sora Neuroscience. Dr. Salter has stock in Owl Therapeutics. The institution of Dr. Salter has received research support from National Multiple Sclerosis Society. The institution of Dr. Salter has received research support from Department of Defense Congressionally Directed Medical Research Program. The institution of Dr. Salter has received research support from Consortium of Multiple Sclerosis Centers. The institution of Dr. Salter has received research support from Multiple Sclerosis Society of Canada.
Brian Sandroff	No disclosure on file
Anthony Feinstein, MD (Sunnybrook Health Sciences Centre)	Anthony Feinstein, MD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis, Biogen, Roche and Sanofi-Genzyme. The institution of Anthony Feinstein, MD has received research support from Multiple Sclerosis Society of Canada. Anthony Feinstein, MD has received publishing royalties from a publication relating to health care.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi;. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi- Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.