Abstract TP067: Baseline Carotid Distensibility Predicts Blood-Brain Barrier Disruption Measured 13 Years Later

Background: Carotid distensibility and stiffness may contribute to white matter hyperintensities (WMH) and blood–brain barrier (BBB) injury. Disruption of the blood–brain barrier (BBB) is linked to progression of WMH into the adjacent normal appearing white matter (penumbra). Dynamic contrast-enhanced (DCE) K trans , and dynamic susceptibility contrast (DSC) K2, derived from Gd enhanced MRI, are indicators of BBB disruption. Hypothesis: We hypothesized that lower carotid distensibility, measured 13 years previously, would predict present BBB disruption within the WMH lesion and its penumbra. Methods: A total of 262 family members of patients with early onset coronary disease, from the GeneSTAR study, underwent carotid ultrasound at baseline as well as at 13-year follow-up along with a 3T MRI brain perfusion scan using Gd enhancement. The penumbra was defined as the area 4 voxels beyond the leading edge of the WMH lesion. Using a linear mixed-effects model controlling for age, sex, race, education, BMI, family relatedness and SBP we calculated mean K trans [s -1 ], and K2 [% signal change] (mean of the top 100 voxels) within the WMH lesion and penumbra at 13 years. Results: Only penumbral K2 was significantly associated with earlier lower carotid distensibility [mmHg -1 ] which predicted higher K2 in the WMH penumbra at 13-year follow-up (β = −1.64, p = 0.029). Mean K trans within the WMH and Penumbra were not significantly associated with carotid distensibility. (Figure 1.) Conclusions: People with lower distensibility and stiffer carotid arteries at baseline were more likely to show greater future BBB permeability within the WMH penumbra (K2) after 13 years. This suggests that long-standing arterial stiffness may set the stage for later, localized BBB disruption within the normal appearing white matter surrounding the WMH lesion. K2 appears to highlight BBB “hot-spots” directly linked to carotid health, suggesting carotids stiffness maybe a potential target for interventions aimed at improving brain health.