ABSTRACT NUMBER: ESOC2026A1518 BLOOD-BRAIN BARRIER DISRUPTION IN PATIENTS WITH INCIDENTAL WHITE MATTER HYPERINTENSITIES

Abstract Background and aims Incidental white matter hyperintensities (WMH) are thought to be part of normal aging. Blood-brain barrier disruption (BBBD) is known to be part of the pathogenesis of WMH in patients with a history of cerebrovascular disease. However the role of BBBD in the development of incidental WMH has not been studied. Here we look at the relationship between the burden and progression of WMH and BBBD in an asymptomatic population with incidental WMH. Methods Patients from the GeneSTAR cohort underwent repeat MRI after 13 years this time including dynamic susceptibility contrast (DSC) assessing for BBBD. WMH volumes were quantified at each visit and normalized to intracranial volume. All variables were log transformed and compared using linear regression. BBBD was compared with the recent WMH volume and changes in WMH volume. Results 315 subjects were included in the cross-sectional analysis, of which 312 were included in the longitudinal analysis. Median age was 64 (62% female). Cross-sectional analysis comparing WMH with BBBD volumes at the recent timepoint strongly correlated (beta=0.334, CI 0.285:0.382, r2=0.61, p<0.001, n=315), while controlling for age, sex and race. Change in BBB was also associated with change in WMH volume (beta=0.092, CI 0.026:0.157, r2=0.11, p=0.006, n=312). Conclusions Incidental WMH volume was in large part explained by the amount of BBB disruption at the time of the MRI. These findings suggest that BBB disruption may be a marker of brain health even in asymptomatic patients. Conflict of interest Richard Leigh: nothing to disclose; Sarvin Sasannia: nothing to disclose; Shimeng Wang: nothing to disclose; Jinwei Zhang: nothing to disclose; Jerry L. Prince: nothing to disclose; Lewis C. Becker: nothing to disclose; Dhananjay Vaidya: nothing to disclose; Peter van Zijl: nothing to disclose; Linda Knutsson: nothing to disclose; Paul A. Nyquist: nothing to disclose;