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Original research
Influence of cardiorespiratory fitness and MRI measures of neuroinflammation on hippocampal volume in multiple sclerosis
  1. Tetsu Morozumi1,
  2. Paolo Preziosa1,2,3,
  3. Alessandro Meani1,
  4. Matteo Albergoni1,
  5. Monica Margoni1,
  6. Elisabetta Pagani1,
  7. Massimo Filippi1,2,3,4,5,
  8. Maria A Rocca1,2,3
  1. 1 Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy
  2. 2 Vita-Salute San Raffaele University, Milano, Italy
  3. 3 Neurology Unit, IRCCS Ospedale San Raffaele, Milano, Italy
  4. 4 Neurorehabilitation Unit, IRCCS Ospedale San Raffaele, Milano, Italy
  5. 5 Neurophysiology Service, IRCCS Ospedale San Raffaele, Milano, Italy
  1. Correspondence to Professor Maria A Rocca, Neuroimaging Research Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano 20132, Italy; rocca.mara{at}hsr.it

Abstract

Background The hippocampus is a clinically relevant region where neurogenesis and neuroplasticity occur throughout the whole lifespan. Neuroinflammation and cardiorespiratory fitness (CRF) may influence hippocampal integrity by modulating the processes promoting neurogenesis and neuroprotection that contribute to the preservation of functions. This study aimed to investigate the effects of neuroinflammation and CRF on hippocampal volume in multiple sclerosis (MS) patients with relapsing-remitting (RR) and progressive (P) clinical phenotypes. The influence of neuroinflammation and CRF on brain, grey matter (GM) and thalamic volumes was also assessed to determine whether the effects were specific for the hippocampus.

Method Brain 3T structural MRI scans and maximum oxygen consumption (VO2max), a proxy of CRF, were acquired from 81 MS patients (27 RR and 54 P) and 45 age-matched and sex-matched healthy controls. T2-hyperintense white matter lesion volume (T2-LV) and choroid plexuses volume (CPV) were quantified as neuroinflammatory measures. Associations of demographic, clinical, neuroinflammatory and CRF measures with normalised brain, GM, hippocampal and thalamic volumes in relapsing-remitting MS (RRMS) and progressive MS patients were assessed using Shapley and best subset selection regression.

Results For most volumetric measures, the largest portions of variance were explained by T2-LV (variable importance (VI)=9.4–39.4) and CPV (VI=4.5–26.2). VO2max explained the largest portion of variance of normalised hippocampal volume only in RRMS patients (VI=16.9) and was retained as relevant predictor (standardised β=0.374, p=0.023) with T2-LV (standardised β=−0.330, p=0.016).

Conclusions A higher CRF may play a specific neuroprotective role on MS patients’ hippocampal integrity, but only in the RR phase of the disease.

  • multiple sclerosis
  • MRI

Data availability statement

Data are available upon reasonable request. The dataset used and analysed during the current study is available from the corresponding author on reasonable request.

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Data availability statement

Data are available upon reasonable request. The dataset used and analysed during the current study is available from the corresponding author on reasonable request.

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Footnotes

  • Twitter @paolopreziosa, @AlbergoniMatteo, @Monica Margoni

  • Contributors Concept and design: MF, MAR; acquisition of data TM, PP, MA, MM; analysis of data TM, PP, AM, EP; drafting/revising of the manuscript: all authors; Guarantor: MAR.

  • Funding This study has been supported by grant from Italian Ministry of Health (GR-2019-12369599).

  • Competing interests PP received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. MM reports grants and personal fees from Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. MF is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, and Fondazione Italiana Sclerosi Multipla. MAR received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; and speaker honoraria from AstraZeneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders.

  • Provenance and peer review Not commissioned; externally peer reviewed.