Journal Article

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

Law, Meng, Cribb, Lachlan, Pase, Matthew P., Vivash, Lucy, O’Brien, Terence J., Pham, William, Cavuoto, Marina, Wang, Danny J. J., Harding, Ian H., Shao, Xingfeng, Chong, Trevor T.-J., Rowsthorn, Ella, Yiallourou, Stephanie, Sinclair, Benjamin

2025

Overview

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. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Aged / Aged, 80 and over / Aging / Aging - physiology / Atrophy / Bayesian analysis / Biomedical and Life Sciences / Biomedicine / Blood flow / Blood vessels / Blood-brain barrier / Blood-Brain Barrier - diagnostic imaging / Brain - blood supply / Brain - diagnostic imaging / Brain health / Brain research / Cerebral blood flow / Cerebrovascular Circulation - physiology / Cohort analysis / Dementia / Diagnostic imaging / Disease / Female / Fluid flow / Fluid transport / Glymphatic clearance / Glymphatic System - diagnostic imaging / Hematology / Homeostasis / Humans / Labeling / Magnetic Resonance Imaging / Male / Mathematical models / Middle Aged / Money / Multi-modal MRI / Multimodal Imaging / Neurobiology / Neurodegenerative diseases / Neuroimaging / Neuroimaging - methods / Neurosciences / Neurovascular unit / Older people / Substantia alba / Vascular health / Water exchange / White Matter - diagnostic imaging