2023 American Academy of Neurology Abstract Website

Tetsu Morozumi¹, Paolo Preziosa³, Matteo Albergoni¹, Monica Margoni², Elisabetta Pagani¹, Alessandro Meani¹, Massimo Filippi⁴, Maria Rocca³
¹Neuroimaging Research Unit, Division of Neuroscience, ²Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, IRCCS San Raffaele Scientific Institute, ³Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, ⁴Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University

Objective:

To investigate whether higher cardiorespiratory fitness (CRF) may limit the detrimental effects of neuroinflammation on hippocampal volume in the main multiple sclerosis (MS) clinical phenotypes.

Background:

The hippocampus is a clinically-relevant brain region that is characterized by neuroplasticity and neurogenesis also in adults. Neuroinflammation and CRF may specifically influence hippocampal integrity, thus modulating the processes promoting neurogenesis and neuroprotection that contribute to the preservation of functions.

Design/Methods:

Brain structural MRI scans and maximum oxygen consumption (VO₂max), a proxy of CRF, were acquired from 81 MS patients (27 relapsing-remitting [RR] and 54 progressive [P]), and 47 age- and sex-matched healthy controls (HC). White matter T2-hyperintense lesion volume (T2-LV) and choroid plexus volume (CPV) were quantified as neuroinflammatory measures. Associations of T2-LV, CPV and CRF with normalized brain (NBV), gray matter (NGMV), thalamic (NTV) and hippocampal volumes were assessed using linear regression analysis. Stepwise hierarchical regression models were used to evaluate the independent contribution of demographic, clinical, T2-LV, CPV and VO₂max in explaining the aforementioned volumes.

Results:

In MS, higher T2-LV was significantly associated with lower global and regional brain volumes (standardized-β from -0.706 to -0.356, p≤0.009), except for NGMV (p=0.105). Higher CPV was significantly associated only with lower NBV and NTV in both RRMS and PMS patients (standardized-β from -0.545 to -0.290, p≤0.045). Higher VO₂max was significantly associated only with higher normalized hippocampal volume only in RRMS patients (standardized-β=0.448, p=0.013). Using stepwise hierarchical regression models, T2-LV in both RRMS (∆R²=0.124, p=0.043) and PMS patients (∆R²=0.095, p=0.028) and VO₂max only in RRMS patients (∆R²=0.153, p=0.014) were found to explain a significant portion of hippocampal volume variance.

Conclusions:

By exerting beneficial neurotrophic effects, a higher CRF may have a specific neuroprotective role for the hippocampus, mainly in the early phases of MS.