AbstractBackgroundIntracranial stenosis (ICS) may contribute to cognitive dysfunction by decreased cerebral blood flow (CBF) which can be measured quantitatively by Arterial Spin Labelling (ASL). Interpretation of CBF measurements with ASL, however, becomes difficult in patients with vascular disease due to prolonged arterial transit time (ATT). Recently, spatial coefficient of variation (sCoV) of ASL signal has been proposed that approximates ATT and utilized as a proxy marker for assessment of hemodynamic status of cerebral circulation. We investigate the association of ICS with CBF and sCoV parameters and its eventual effects on cognition in a memory clinic population.MethodWe included 381 patients (mean age = 72.3 ± 7.9 years, women = 53.7%) who underwent 3T MRI and detailed neuropsychological assessment. ICS was defined as ≥ 50% stenosis in any intracranial vessel on 3D Time‐of‐Flight MR Angiography. Gray matter sCoV and CBF were obtained from 2D EPI pseudo‐continuous ASL images. We used regression models to determine the effects of ICS on CBF and sCoV and eventually on cognition. Mediation analysis was further constructed to determine whether perfusion is the key link between ICS and cognitive performance. All analyses were adjusted for age, sex, hypertension, hyperlipidemia and diabetes.ResultICS was present in 58 (15.2%) patients. Patients with ICS had higher gray matter sCoV and lower CBF. The association with sCoV remained statistically significant after correction for cardiovascular risk factors. Moreover, ICS was associated with worse performance on visuoconstruction, which attenuated with higher sCoV. Mediation analysis showed that there was an indirect effect of ICS on visuoconstruction via sCoV.ConclusionThese findings suggest that compromised CBF as detected by higher sCoV is related to cognitive impairment among individuals diagnosed with ICS. We also showed that sCoV partially mediates the link between ICS and cognition. Therefore, sCoV may provide valuable hemodynamic information in patients with vascular disease.