Cognitive deficits across a range of domains and degrees of severity are commonly observed in patients with RRMS and can significantly impact their quality of life. The heterogeneity reflects the complex underlying neuropathology of this disease. For this reason, it is still unclear which MS-related brain pathology predominantly affect cognition and whether different cognitive domains are preferentially affected.

Significant decline in attention, memory and executive function abilities was observed in patients with RRMS compared to HC. Moreover, patients showed volumetric reductions in white matter (WM), thalamus and parahippocampal gyrus, decreased brain stem FA, increased FC in the anterior default-mode network (DMN) and decreased FC in the posterior DMN and both fronto-parietal networks. Attention performance was associated with both macro- and micro-structural WM damage and mainly driven by disease duration. No significant associations were found between alterations in FC across brain networks and either cognitive or non-cognitive symptoms.