LAUSR

Introduction: Sex differences in white matter hyperintensity (WMH) burden exist and are affected by menopausal status. Here, we investigate the difference in age-related WMH burden with respect to stroke subtype (TOAST) and menopausal status. Methods: We reviewed 4443 patients across 18 sites with information on age, TOAST, prior stroke, hypertensive (HTN) and diabetic (DM2) status, smoking history, and WMH and brain volume. WMH load was defined as the ratio between WMH and brain volume and Box Cox transformed. All variables underwent z-score standardization. Pre- (PRM), peri- (PEM), and post-menopausal (POM) categories were defined using age (PEM: 45-59 years). WMH load was modeled using age, prior stroke, HTN, DM2, smoking status, and interaction terms between age, TOAST, and sex/menopausal status. A second model included TOAST as an independent variable. Models accounted for acquisition site and were compared using Bayes Information Criteria (BIC). Significance was set to p<0.05. Results: Of all patients (median age: 64), 42% were female (6%, 10%, and 26% PRM, PEM, and POM, respectively). The model without TOAST as an independent variable was selected (BIC 9237 compared to 9779). Our results (Figure 1) show (beta [95% confidence interval]) prior stroke (0.22 [0.15-0.29]), smoking (0.09 [0.04-0.14]), HTN (0.19 [0.14-0.25]), DM2 (0.08 [0.01-0.15]), and age (0.54 [0.43-0.65]) as independent factors. TOAST did not affect age-related WMH load in men and PRE. Effects of age were modified for small artery occlusion strokes in POM (0.40 [0.03-0.76]), increasing the age-related disease burden. Conclusions: Menopausal status affects age-related WMH burden for different TOAST.