Evidence map›Paper›PMID 40986118›Full record

Trial reportJournal of neurology2025

Effects of cognitive rehabilitation and exercise on brain structure in progressive multiple sclerosis: results from the CogEx trial.

Francesco Romanò, Maria A Rocca, Elisabetta Pagani, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D Chiaravalloti, Gary Cutter, Ulrik Dalgas, John DeLuca and 12 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03679468 (Improving Cognition in People With Progressive Multiple Sclerosis), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03679468 nacompletednot on this map

Improving Cognition in People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial of Cognitive Rehabilitation and Aerobic Exercise.

TypeinterventionalSponsorSunnybrook Health Sciences CentreRan2019 to 2023Enrolled309ConditionsMultiple Sclerosis, Primary Progressive, Cognitive ImpairmentArmsCognitive Rehabilitation, Sham Exercise, Sham Cognitive Rehabilitation, Aerobic Exercise
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Francesco RomanòNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.ORCID http://orcid.org/0009-0009-1637-0501
Maria A RoccaNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.ORCID http://orcid.org/0000-0003-2358-4320
Elisabetta PaganiNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Maria Pia AmatoDepartment NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy.
Giampaolo BrichettoScientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
Jeremy ChatawayFaculty of Brain Sciences, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, WC1B 5EH, UK.
Nancy D ChiaravallotiKessler Foundation, West Orange, NJ, USA.
Gary CutterDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Ulrik DalgasExercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.
John DeLucaKessler Foundation, West Orange, NJ, USA.ORCID http://orcid.org/0000-0002-2767-3382
Rachel FarrellFaculty of Brain Sciences, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, WC1B 5EH, UK.
Peter FeysFaculty of Rehabilitation Sciences, REVAL, Hasselt University, Diepenbeek, Belgium.ORCID http://orcid.org/0000-0002-5680-5495
Jennifer FreemanFaculty of Health, School of Health Professions, University of Plymouth, Devon, UK.ORCID http://orcid.org/0000-0002-4072-9758
Matilde IngleseDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Emilio CiprianoDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Cecilia MezaDepartment of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Canada.
Robert W MotlDepartment of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA.
Amber SalterDepartment of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, TX, USA.
Brian M SandroffKessler Foundation, West Orange, NJ, USA.
Anthony FeinsteinDepartment of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Canada.
Massimo FilippiNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it.ORCID http://orcid.org/0000-0002-5485-0479
CogEx Research Team

Funding

Multiple Sclerosis Society of Canada EGID 3185)
6 · The paper itself

Abstract

backgroundWe previously showed increased cortical grey matter (GM) volume in CogEx trial participants who performed cognitive rehabilitation (CR). Here, we explore combined CR and aerobic exercise (EX) effects on regional changes in brain volumes and white matter (WM) integrity.

methodsSeventy-three patients were randomized into four groups receiving a combination of CR and EX or their sham versions: CR + EX, CR + EX-sham, EX + CR-sham, and CR-sham + EX-sham. A diagnosis of progressive multiple sclerosis (PMS) and impaired information processing speed were required for inclusion. Participants attended a 12-week intervention twice/week. Assessments were performed at baseline, week-12 (W12), and nine months post-baseline (M9). Structural MRI scans were acquired with a standardized protocol, and voxelwise variations of brain volumes and WM fractional anisotropy (FA) were analyzed.

resultsBaseline regional brain volumes and WM FA were comparable between groups. Voxelwise analyses at W12 and M9 revealed generalized volume reductions in all groups. We found different patterns of volumetric changes in the left inferior temporal gyrus between CR + EX and CR-sham + EX-sham, and in the right cerebellum crus II between EX + CR-sham and CR + EX-sham. WM FA values remained stable throughout the trial and no longitudinal between-group differences were found.

conclusionsOur analysis showed a decrease in brain volumes and limited effects of the combined CR + EX intervention, indicating that the previously found cortical GM increase was not superimposable at voxel level. Methodological and sampling differences between the studies could explain these discrepancies. In few cognitively relevant areas, the combined CR interventions might have affected patterns of volume changes, while EX modified cerebellar motor regions. CLINICAL

trial registrationThe main trial was registered on ClinicalTrials.gov (NCT03679468; registration date: 20 Sep 2018).

Indexed as

BrainExercise TherapyMultiple Sclerosis, Chronic ProgressiveAdultCognitive TrainingDiffusion Tensor ImagingFemaleGray MatterHumansMagnetic Resonance ImagingMaleMiddle AgedWhite MatterCognitive RehabilitationExercise TherapyMagnetic Resonance ImagingMultiple SclerosisNeuroplasticityVoxelwise

Identifiers

PMID40986118
PMCPMC12457549

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.