Mild cognitive decline in people with relapsing-remitting multiple sclerosis: a major role of structural over functional brain alterations. (2216)

Objective: This study investigated the differences in the relationship between performance decline in different cognitive domains in patients with relapsing-remitting multiple sclerosis (RRMS) and measures of structural and functional brain damage. Background: 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. Design/Methods: Cognitive performance across different domains, brain volume, fractional anisotropy (FA) and resting-state fMRI functional connectivity (FC) were compared between forty patients with RRMS (EDSS = 3.5 ± 1.5) and twenty-five healthy controls (HC). The relationship between cognitive performance of patients with RRMS and various MS-related symptoms and different indices of structural and functional alterations was also investigated. Results: 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. Conclusions: This study shows that mild cognitive decline in attention abilities of patients with RRMS appears to be associated prominently with WM damage, while no relationship was detected between alterations in resting-state FC and cognitive performance. Further studies are needed to clarify the differential impact of both structural and functional brain damage in patients with more severe impairment in different cognitive domains. Disclosure: Dr. Manca has nothing to disclose. Dr. Sharrack has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Sharrack has received research support from Biogen, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Venneri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck a Co.