Thalamic nuclei volume partially mediates the effects of aerobic capacity on fatigue in people with multiple sclerosis
Description
Fatigue is a prevalent and disabling symptom in people with multiple sclerosis (pwMS), affecting both cognitive and physical domains. This study explored the relationship between aerobic capacity, thalamic nuclei volumes, and fatigue, and assessed whether thalamic integrity mediates the effect of aerobic fitness on fatigue perception. The study retrospectively enrolled 83 pwMS (36 with relapsing–remitting MS and 47 with secondary progressive MS) and 63 age- and sex-matched healthy controls (HC). All participants underwent 3T brain MRI to quantify thalamic and global brain volumes. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), and aerobic capacity was assessed via peak oxygen uptake (VO₂peak) from cardiopulmonary exercise testing (CPET), available for all pwMS and 22 HC. Compared to HC, pwMS exhibited significantly lower VO₂peak and thalamic volumes and higher global, physical, and cognitive fatigue scores. In pwMS, higher VO₂peak was associated with lower fatigue (MFIS and pMFIS) and with greater volume in the laterodorsal thalamic nuclei cluster (Dor). Furthermore, lower Dor volume was linked to greater fatigue in all MFIS domains. Mediation analyses revealed that the Dor cluster partially mediated the beneficial effects of VO₂peak on global fatigue (21% indirect effect) and cognitive fatigue (32% indirect effect), but not physical fatigue. These findings suggest that aerobic capacity influences fatigue in pwMS, partly via structural preservation of specific thalamic subregions, especially the laterodorsal nuclei. While physical fatigue may be more directly influenced by systemic or extra-thalamic factors, cognitive fatigue appears partially dependent on thalamic integrity. This underscores the potential neuroprotective role of cardiorespiratory fitness and highlights the Dor thalamic cluster as a critical neural substrate in MS-related fatigue. Targeting aerobic capacity through rehabilitation may not only alleviate fatigue but also support thalamic structural integrity in pwMS.
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Ministero della Salute
GR-2019-12369599