High estimated pulse-wave velocity is associated with lower brain white matter microstructural integrity twelve years later.

High pulse wave velocity (PWV), a measure of increased arterial stiffness, is a risk factor for cerebrovascular disease. PWV can be estimated (ePWV) from age and blood pressure (BP). Elevated ePWV is associated with cerebral small-vessel disease, cognitive decline, and dementia risk in middle-aged and older adults. We examined data from the Midlife in the United States (MIDUS) Neuroscience Project to examine the association of ePWV with brain white matter microstructure. BP was measured in 132 middle-aged adults (mean age 53+/- 10 years, n = 77 women, n = 38 Black/African American) between 2004 and 2009 and used to calculate ePWV. Diffusion-weighted imaging (DWI) data were acquired between 2017 and 2022 and used to estimate: global white matter fractional anisotropy; axial, radial, and mean diffusivity and kurtosis; neurite density index; and orientation dispersion index. High ePWV was associated with: lower fractional anisotropy; axial, radial, and mean kurtosis; and neurite density index. High ePWV was also associated with higher axial, radial, and mean diffusivity, and orientation dispersion index. Except for axial diffusivity/kurtosis and orientation dispersion, all associations between high ePWV and white matter microstructure remained after adjusting for exogenous controls (sex and race), education, the constituent components of ePWV (age and blood pressure), and the time lag between BP and DWI measures. In conclusion, high ePWV in middle-aged adults is prospectively associated with compromised brain white matter microstructure more than a decade later. ePWV may be a useful metric of vascular aging that can be applied to the study of brain aging.