Perivascular space volumes relate to arterial stiffness and cognition

Abstract

AbstractBackgroundEnlarged perivascular spaces (PVS) are a marker of small vessel disease (SVD). PVS in the basal ganglia are associated with hypertensive damage to arteries and arterioles; however, prior work relating arterial stiffness to changes in PVS have been inconclusive. Additionally, clinical consequences of PVS are poorly understood, possibly due to reliance on manual rating systems that lack precision. This study used an automated process to measure basal ganglia PVS count and volume and cross‐sectionally assess their associations with central arterial stiffness and cognition.MethodVanderbilt Memory and Aging Project participants free of clinical stroke and dementia (n=327, 73±7 years, 41% female) completed T1‐weighted brain MRI to measure PVS burden, neuropsychological assessment, and cardiac MR to quantify pulse wave velocity (PWV) in the thoracic aorta, a marker of central arterial stiffness. PVS volume and count were quantified using an automated approach. Basal ganglia volume and count measures were log‐transformed. Linear regression models related PWV separately to PVS volume and count adjusting for demographic and health variables, apolipoprotein E‐e4 status, and intracranial volume. Models were repeated separately relating PVS volume and count to neuropsychological performance with identical covariates.ResultHigher PWV related to greater basal ganglia PVS volume (b=7.0e‐5, p=0.04) and count (b=0.02, p=0.03). When excluding outliers, PVS volume results were attenuated (p=0.17) but count results persisted (p=0.03). Higher PVS volume was associated with worse sequencing (b=1560, p=0.002), digit symbol (b=‐979, p=0.003), executive function (b=‐82.3, p<0.001), and visuospatial performances (b=‐193, p=0.02). Cognitive results were comparable for models using PVS count as the predictor.ConclusionCentral arterial stiffness is associated with greater PVS burden in the basal ganglia. Findings support the hypothesis that increased aortic stiffness and resulting changes in hemodynamics essential for maintaining perfusion pressure may result in PVS damage. Greater PVS burden is associated with worse cognitive performance, primarily on tests of executive function and information processing, aligning with our prior findings relying on a manual PVS rating system. PVS may account for damage to frontal subcortical networks which integrate the basal ganglia and play an important role in executive function and information processing. Funding: F31‐AG066358, T32‐AG058524, Alzheimer’s Association IIRG‐08‐88733, R01‐AG034962, R01‐AG056534, K24‐AG046373, P20‐AG068082