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Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. The authors conclude that hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS.