Association of stenosis and arterial remodeling with cerebral hemodynamics and cognition

Background Associations between intracranial stenosis, arterial remodeling, cerebral hemodynamics, including cerebral blood flow (CBF) and arterial transit time (ATT), white matter hyperintensities (WMH), and cognition remain unclear. Objective This study investigates the relationships between MRA-derived vascular parameters, cerebral hemodynamics, WMH burden, and cognition. We hypothesized that greater stenosis or remodeling is associated with impaired hemodynamics, increased WMH burden, and poorer cognition. Methods Cross-sectional study of 452 memory clinic patients (median age 74 [IQR 68–78], 53% female) who underwent 3T MRI with time-of-flight MRA and pseudo-continuous ASL. Automated quantification derived global stenosis and brain arterial remodeling (BAR) scores. CBF and spatial coefficient of variation (sCoV) assessed hemodynamics; WMH volume from FLAIR; cognition from a validated neuropsychological battery. Structural equation modelling (SEM) evaluated associations, adjusting for demographics and cardiovascular risk factors. Results Higher sCoV was associated with higher BAR (β = 0.14, 95% CI:0.06–0.23). WMH was associated with stenosis (β = 0.20, CI:0.12–0.28) and BAR (β = 0.07, CI:0.001–0.140). Lower CBF (β = -0.26, CI:-0.36 to −0.15) and higher sCoV (β = 0.27, CI:0.17–0.36) were associated with greater WMH burden. Higher BAR was associated with better global cognition (β = 0.07, CI:0.00–0.14). SEM indicated indirect associations with cognition via WMH and CBF. Conclusions Vascular remodeling and stenosis are associated with cerebral hemodynamics, WMH, and cognition, with CBF and WMH as potential mediators, underscoring the importance of vascular health in Alzheimer's disease. These direct and indirect associations are not mutually exclusive: higher BAR was associated with better cognition directly, while also relating to poorer cognition indirectly through greater WMH burden and perfusion heterogeneity.