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; Cogex Research Team

doi:10.1136/jnnp-2024-333460

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

J Neurol Neurosurg Psychiatry. 2024 May 16:jnnp-2024-333460. doi: 10.1136/jnnp-2024-333460. Online ahead of print.

Authors

Maria A Rocca^{1

2

3}, Paola Valsasina⁴, Francesco Romanò⁴, Nicolò Tedone⁴, Maria Pia Amato^{5

6}, Giampaolo Brichetto^{7

8}, Vincenzo Daniele Boccia⁹, Jeremy Chataway^{10

11}, Nancy D Chiaravalloti^{12

13}, Gary Cutter¹⁴, Ulrik Dalgas¹⁵, John DeLuca^{12

13}, Rachel A Farrell¹⁰, Peter Feys^{16

17}, Jennifer Freeman¹⁸, Matilde Inglese^{9

19}, Cecilia Meza²⁰, Robert W Motl²¹, Amber Salter²², Brian M Sandroff^{12

13}, Anthony Feinstein²⁰, Massimo Filippi^{4

2

3

23

24}; Cogex Research Team

Collaborators

Cogex Research Team:
Anne Sophie Michelsen, Laurits EmilTaul Madsen, Marie-LouiseKjeldgaard Jørgensen, Mette Dahl Diedmann, Charly Keytsman, Ellen Vanzeir, Leen Knevels, Mieke D'Hooge, Renee Veldkamp, Rudi Donnee, Séline Vandecasteele, Veerle Vandael, Claudio Cordani, Mauro Sibilia, Carmen Vizzino, Gianna Carla Riccitelli, Paolo Preziosa, Jessica Podda, Ludovico Pedullà, Andrea Tacchino, Angela Smith, Blake Bichler, Jimmy Morecraft, Michael DiBenedetto, Nancy Moore, Catherine Holme, Chris Cole, Kimberley Algie, Sara Chatfield, Juliana Puopolo, Laura Kenton, Laura Toll, Ashlie Kristin Ithurburn, Brendon Truax, Catherine Danielle Jones, Jessica Baird, Petra Silic, Michelle Koch, Patrizia Pajak, Alexsandra Pietrusz, Catherine Smith, Holly Wilkinson, James Braisher, Marie Braisher, Rebecca Bex Walters, Claudia Niccolai, Guido Pasquini, Irene Mosca, Sara Della Bella, Fedrica Vannetti, Filippo Gerli, Chiara Pollio, Eleonora Colombo, Elisa Pelosin, Maria Cellerino, Matteo Pardini, Roberto Hernandez, Joke Lenaerts, Natasja De Weerdt, Michele Curran

Affiliations

¹ Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy rocca.mara@hsr.it.
² Neurology Unit, IRCCS Ospedale San Raffaele, Milan, Italy.
³ Vita-Salute San Raffaele University, Milan, Italy.
⁴ Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy.
⁵ Department NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy.
⁶ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
⁷ Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
⁸ AISM Rehabilitation Service, Italian Multiple Sclerosis Society, Genoa, Italy.
⁹ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
¹⁰ Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
¹¹ National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK.
¹² Kessler Foundation, West Orange, NJ, USA.
¹³ Department of Physical Medicine & Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
¹⁴ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁵ Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.
¹⁶ REVAL, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.
¹⁷ University MS Center, Hasselt University, Pelt, Belgium.
¹⁸ Faculty of Health, School of Health Professions, University of Plymouth, Plymouth, Devon, UK.
¹⁹ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
²⁰ Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
²¹ Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, Illinois, USA.
²² Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, Texas, USA.
²³ Neurorehabilitation Unit, IRCCS Ospedale San Raffaele, Milan, Italy.
²⁴ Neurophysiology Service, IRCCS Ospedale San Raffaele, Milan, Italy.

PMID: 38754979
DOI: 10.1136/jnnp-2024-333460

Abstract

Background: Research 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.

Methods: Participants 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).

Results: 104 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.

Conclusions: In 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 number: NCT03679468.

Keywords: COGNITION; MRI; MULTIPLE SCLEROSIS; REHABILITATION.

Associated data

ClinicalTrials.gov/NCT03679468