BACKGROUND AND PURPOSECerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricular CSF and subarachnoid space (sulcal CSF). Changes in CSF volumetry are seen in many neurological conditions including multiple sclerosis (MS) and found to correlate with clinical outcomes. We aimed to test the relation between the volumetry of sulcal and ventricular CSF and cognitive impairment (CI) based on the minimal assessment of cognitive function in MS (MACFIMS) in patients with MS. MATERIAL AND METHODSForty-six patients with MS underwent the MACFIMS battery and classified as nonimpaired (MSNI) (n = 10) and cognitively impaired (MSCI) (n = 30) and borderline (MSBD) MS patients (n = 6). Volumes of sulcal and ventricular CSF along with global gray and white matter volumes and cortical thickness were obtained by diffusion tensor imaging (DTI) and T1-weighted (T1w)-based segmentation. These measures were statistically analyzed for associations with CI after adjusting for the age, education in years, lesion load, and disease duration. RESULTSSulcal CSF showed the strongest correlation with CI (r = .51, P = .001) in our cohort, whereas ventricular CSF (P = .28, P = .19) along with cortical thickness and gray matter volume failed to show a significant correlation. Group analyses unadjusted for multiple comparisons showed significant difference in volumes of sulcal CSF and ventricular CSF between MSNI and MSCI groups (P < .05). CONCLUSIONSulcal CSF correlates with CI in patients with MS, possibly explained by cortical atrophy. DTI/T1w-based sulcal CSF segmentation method might be used as an indirect and simple neuroimaging marker to monitor CI in MS patients.