Arterial Spin Labeling Hemodynamic Indices Relate to Cognitive and Small Vessel Disease Trajectories Over 11 Years.

Abstract

Hemodynamic insufficiency may contribute to the development of neuroimaging signs of cerebral small vessel disease (SVD). The arterial spin labeling (ASL) spatial coefficient of variation (ASL-sCoV) is a proxy marker of arterial transit time and may better capture SVD-related hemodynamic disturbances compared with ASL-derived cerebral blood flow. We investigated ASL-derived hemodynamic indices in relation to cognition and neuroimaging markers of SVD over an 11-year follow-up period. Participants without dementia or stroke were enrolled in the Vanderbilt Memory and Aging Project, a longitudinal observational cohort study in Nashville, TN. Participants underwent serial multimodal 3T brain magnetic resonance imaging to quantify SVD burden and neuropsychological assessment from 2012 to 2024 (4.9±3.5 years mean follow-up). Pseudo-continuous ASL assessed cerebral blood flow and ASL-sCoV in total gray matter. Baseline ASL-sCoV and cerebral blood flow were individually related to the cross-sectional burden and longitudinal trajectory of each SVD neuroimaging marker (white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, and lacunar infarcts) and cognitive performances using linear and linear mixed-effects regression models. Models were adjusted for demographics, cognitive status, Framingham Stroke Risk Profile (minus age), <i>apolipoprotein E</i>-ε4 status, intracranial volume (for SVD outcomes), and follow-up time (for longitudinal models). Among participants (n=667, 68±9 years, 18% mild cognitive impairment, 51% female), higher ASL-sCoV was cross-sectionally associated with SVD markers, including white matter hyperintensities and enlarged perivascular spaces (<i>p</i>_FDR-values<0.006). Higher baseline ASL-sCoV was associated with a faster longitudinal increase in the burden of white matter hyperintensities (<i>p</i>_FDR=0.03) and accelerated decline in executive function, information processing, language, and visuospatial performances (<i>P</i><0.05). Gray matter cerebral blood flow was not associated with SVD burden or cognition cross-sectionally (<i>p</i>_FDR-values>0.05) or longitudinally (<i>p</i>_FDR-values>0.06). ASL-sCoV may serve as an important hemodynamic measure for identifying perfusion deficits tied to SVD burden and progression. Readily derived from existing ASL data sets, ASL-sCoV could provide substantial insight into the longitudinal clinical consequences of SVD.