Lower total cerebral arterial flow contributes to cognitive performance in multiple sclerosis patients

Background: The cognitive performance in multiple sclerosis (MS) patients declines with aging, longer disease duration, and possibly cardiovascular comorbidities. Objectives: We investigated whether lower total cerebral arterial blood flow (CABF) measured at the level of the carotid and vertebral arteries may contribute to worse cognitive performance in 132 MS patients and 47 healthy controls. Methods: Total CABF was evaluated with extracranial Doppler, whereas structural T2-lesion volume (LV) and gray matter volume (GMV) were measured on 3T MRI. The cognitive performance was assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and California Verbal Learning Test-Second Edition (CVLT-II). Analysis of covariance, partial correlation, and regression models were used to test the differences between study groups and cognition/CABF correlations. False discovery rate (FDR)-corrected (Benjamini-Hochberg) p-values (i.e. q-values) less than 0.05 were considered significant. Results: Association between lower total CABF and the lower cognitive performance was observed only in MS patients (r = 0.318, q < 0.001 and r = 0.244, q = 0.012 for SDMT and BVMT-R, respectively). Lower GMV, higher T2-LV, and CABF were significantly associated with poorer performance on the processing speed measure of SDMT (adjusted R-2 = 0.295, t-statistics = 2.538, standardized beta = 0.203, and q = 0.020), but not with memory tests. Cognitively impaired MS patients had lower total CABF compared to cognitively preserved (884.5 vs 1020.2 mL/min, q = 0.008). Conclusion: Cognitively impaired MS patients presented with lower total CABF. Altered CABF may be a result of reduced metabolic rate and might contribute to abnormal cognitive aging in MS.