AAN 2026 | Aerobic training and its potential impact on neurogenesis in progressive multiple sclerosis

The aim of the study was to evaluate the effects of aerobic exercise on hippocampal subfield volumes and on the microstructure of the subventricular zone in patients with progressive multiple sclerosis and also to explore possible associations between changes of these MRI metrics and changes in clinical outcomes because the rationale for the study was based on the evidence suggesting that neurogenesis may occur also in the adult mammalian brain in specific regions which are the dentate gyrus of the hippocampus and in the subventricular zone. And this is clinically relevant since the atrophy of the hippocampus and the microstructural damage of the subventricular zone have been associated with depression and with cognitive deterioration. So we know also that aerobic exercise seems to exert a neuroprotective role on the brain, and this especially also by improving, by enhancing neurogenesis. So, for example, previous studies have found an association between peak oxygen consumption and hippocampal volume, not only in patients with relapsing-remitting multiple sclerosis. So we hypothesize that maybe a more detailed segmentation of the hippocampus and its subfields and inclusion of the subventricular zone into the analysis could reveal effects of aerobic exercise also on progressive multiple sclerosis patients.

So we retrospectively analyzed data from 84 patients with progressive MS who were enrolled at four sites participating through the COGX MRI sub-study. And they were randomized into one group performing aerobic training and one group performing a balance and stretching-based sham exercise intervention, both for three months. At baseline, post-intervention, and at a six-month follow-up, patients underwent clinical assessment and also MRI acquisition on a three-Tesla scanner. And then we used a FreeSurfer longitudinal processing stream to segment the hippocampus into its subfields. So we obtained the different subfields, for example, the cornu ammonis in its different parts, the subiculum and the dentate gyrus, and we obtained their volume. While regarding the subventricular zone, we extracted the values of fractional anisotropy and mean diffusivity in this area. So what we found was that the dentate gyrus volume increased between baseline and post-treatment, but only in patients in the aerobic group, as we expected. And this increase was largely maintained also at the six-month follow-up. While no significant changes were found in the other subfields and also in the subventricular zone. However, we found no significant associations between this increase in the dentate gyrus volume and changes in the clinical outcomes of cognitive function and depression. This may be due to the fact that maybe the training period was too short to detect such an association or the sample size was too low. But in any case, our findings support the integration of aerobic exercise into the clinical management of progressive MS patients, as it shows that also in this more advanced phase of the disease, it may have a neuroprotective role on the dentate gyrus. And as we know, the hippocampus is one of the major sites of atrophy in MS patients.

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