Relationships between measures of neurovascular integrity and fluid transport in aging: a multi-modal neuroimaging study

Fluid transport in the neurovascular unit is essential for maintaining brain health through nutrient delivery and waste clearance. However, these systems are complex and the inter-dependencies between elements of these systems and how they may change through aging is not well understood. MRI outcomes provide insight into the underlying biological mechanisms of these systems in vivo, including water exchange rate through the neurovascular unit (BBB k_w), enlarged perivascular spaces (ePVS), cerebral blood flow (CBF), free water (FW), and white matter hyperintensities (WMH). To explore the relationships between functional elements of the neurovascular unit, this study investigated relationships between these MRI measures using Bayesian mixed models, and their variation with chronological age or atrophy-related brain age (brainageR) using linear regression. In 132 non-clinical older adults (mean age = 67 years; 68% female), BBB k_w positively associated with CBF (β^ = 0.08, 95% credible interval (CI) = [0.02, 0.15]). FW positively associated with both ePVS (β^ = 0.44, CI = [0.30, 0.63]) and WMH (β^ = 0.13, CI = [0.04, 0.21]). BBB k_w, CBF and ePVS decreased with age, while FW and WMH increased (all p < 0.05). There were no associations with atrophy-related brain age (all p > 0.05). Relationships between FW, ePVS and WMH likely reflect interconnectivity of fluid regulation within different compartments, while the relationship between BBB k_w and CBF indicates a link between neurovascular fluid flow and vessel function. While individual metrics of neurovascular integrity are associated with age, their inter-relationships appear stable, providing a baseline for future research in fluid transport and vascular health in neurodegenerative disease.