Abstract
Cognitive impairment is a core non-motor symptom of Parkinson's disease (PD), yet its biological substrates remain poorly defined. Emerging evidence implies cerebrovascular involvement, although direct investigations of the cerebrovasculature are scarce. This study used 4D flow MRI and Bayesian multi-level modelling to explore the health of the circle of Willis (CoW) in PD, and to examine whether anatomical or haemodynamic changes within this network relate to cognitive and motor symptoms. Arterial anatomy (cross sectional area) and haemodynamics (mean flow, total cerebral blood flow, mean and maximum velocity, pulsatility, and resistance) were assessed in 80 individuals with PD with varying levels of cognitive and motor impairment, and 34 controls. Compared to controls, PD was associated with lower mean flow, total cerebral blood flow, and mean velocity across the CoW network. Altered haemodynamics (lower mean flow and mean velocity) were associated with both cognitive and motor impairment, while vascular stiffening (increased pulsatility and resistance) exclusively co-occurred with cognitive decline. Our results identify CoW dysfunction as a pathophysiological feature of PD and implicate compromised haemodynamics in symptom severity. Findings position the cerebrovasculature as a potential target for therapeutic focus.