Cardiac diseases with elevated central venous pressure have higher frequency of jugular venous reflux (JVR), which is associated with decreased cerebral blood flow and white matter hyperintensities. Whether patients with severe mitral-regurgitation (SMR) have poorer cognitive functions and whether JVR is involved were determined in this pilot study. Patients with SMR and age/sex-matched controls were prospectively recruited. Neuropsychological tests such as global cognitive (Mini-Mental State Examination, MMSE), verbal memory, executive, and visuospatial domains were performed. Cardiac parameters by cardiac catheterisation and echocardiography, and the frequency of JVR by colour-coded duplex ultrasonography were obtained. Forty patients with SMR and 40 controls (71.1±12.2, 38-89 years; 75% men) were included. Compared with the controls, patients with SMR had lower scores in all neuropsychological tests but only MMSE and visuospatial test scores were statistically significant after adjusting for age, sex, and educational level. We further adjusted for cardiovascular risk factors; the significance remained in the visuospatial test but diminished in MMSE. Multivariate linear regression analyses adjusted for age, sex, and educational level showed that JVR combined with high right-atrial-pressure (RAP > 50th-percentile, 12 mmHg) was significantly associated with poorer performances in both MMSE [right JVR: B coefficient(95% confidence interval,p) = -2.83(-5.46-0.20, 0.036); left JVR: -2.77(-5.52-0.02, 0.048)] and visuospatial test [right JVR: -4.52(-8.89-0.16, 0.043); left JVR: -4.56(-8.81-0.30, 0.037)], with significances that remained after further adjusting for cardiovascular risk factors. Our pilot results suggest that retrogradely-transmitted venous pressure might be involved in the mechanisms mediating the relationship between cardiac diseases and brain functions.