Regional White Matter Hyperintensities are Associated with Diminished Blood Flow and Microstructure in Middle Age

Abstract

AbstractBackgroundWhite matter hyperintensities (WMH) are areas of increased signal visualized on T2‐weighted FLAIR magnetic resonance imaging (MRI), thought to reflect macrostructural damage due to small vessel cerebrovascular disease. Previous work established an association of WMH severity, particularly in posterior regions, with risk and progression of AD in late onset and genetic forms of AD, suggesting a vascular component to disease pathogenesis and course. Examination of the emergence and correlates of cerebrovascular changes in middle age, a critical time when vascular risk appears to be most penetrant, can give insight into mechanisms linking vascular brain injury and risk for AD. In the current study, we examined the association of cerebral blood flow (CBF) and white matter microstructure with total and regional WMH volume in middle‐aged, community dwelling adults.MethodFour hundred and ninety‐two middle‐aged participants (55+/‐11 age = 28 ‐85 years) from the community‐based Offspring Study of Mechanisms for Racial Disparities in Alzheimer’s Disease received multi‐modal MRI scanning. Regional WMH volumes were derived with in‐house software that labeled clusters of voxels within a hyperintense intensity distribution. Pulsed arterial spin labeling (PASL) sequences were processed to quantify CBF. Fractional anisotropy (FA) maps were obtained from diffusion weighted data. Total and regional WMH volumes were used as predictors for whole brain voxel‐wise correlation analyses in separate models for CBF and FA.ResultThere were negative associations between WMH volume and CBF in frontal, parietal, and occipital regions. Higher white matter hyperintensity volume was associated with lower FA, particularly in the periventricular region.ConclusionWe found associations of increased WMH volume with diminished blood flow and white matter microstructure. Future studies are needed to explain the relationship between these changes and the risk of cognitive impairment in middle aged adults and risk for AD.