DT MRI microstructural cortical lesion damage does not explain cognitive impairment in MS

Objective: We combined double inversion recovery (DIR) and diffusion tensor (DT) magnetic resonance imaging (MRI) to quantify the severity of cortical lesion (CL) microstructural tissue abnormalities in a large cohort of relapse-onset multiple sclerosis (MS) patients and its contribution to cognitive dysfunction. Methods: DIR, DT, dual-echo, and three-dimensional (3D) T₁-weighted scans were acquired from 149 MS patients and 40 controls. Cognitively impaired (CI) patients had ⩾2 abnormal neuropsychological tests. Diffusivity values in CLs, cortex, white matter (WM) lesions, and normal-appearing (NA) WM were assessed. Predictors of cognitive impairment were identified using a random forest analysis. Results: Compared to controls, MS patients had lower normalized brain volume (NBV), gray matter volume (GMV), WM volume, lower fractional anisotropy (FA), and higher mean diffusivity in cortex and normal-appearing white matter (NAWM). A total of 44 (29.5%) patients were CI. Compared to cognitively preserved (CP), CI patients had higher T₂ WM lesion volume (LV), lower NBV and GMV, and more severe diffusivity abnormalities in WM lesions, cortex, and NAWM. CL measures did not differ between CI and CP patients. Cortex FA, age, disease duration, T₂ WM LV, and GMV best predicted MS-related cognitive impairment (C-statistic = 0.88). Conclusion: “Diffuse” GM and NAWM damage and WM lesions, rather than intrinsic CL damage, contribute to cognitive impairment in MS.