Obesity and Race May Explain Differential Burden of White Matter Hyperintensity Load

Objective: Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans. Methods: Participants enrolled in longitudinal brain aging studies (n=292; 61% Female; 92% European American; mean age=69.6± 7.7) completed evaluations including medical exams, neuroimaging, and sociodemographic surveys. Overweight/obese status defined as body mass index ≥ 30 kg/m 2 , and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0– 6), WMH≥ 4 considered high. Results: Logistic regression analyses, adjusted for age, sex, hypertension, and smoking history, indicated that age and interaction between race and obesity were significant predictors of WMH, demonstrating that obesity significantly moderated the relationship between race and WMH. Age independently increased the odds of high WMH by 16% (OR=1.16, 95% CI=1.09– 1.23, p< 0.001). Stratified analysis indicates that older European Americans had increased WMH (OR=1.17, 95% CI=1.09– 1.23, p< 0.001), while obese African Americans had increased WMH (OR=27.65, 95% CI=1.47– 519.13, p< 0.05). In a case controlled subgroup matched by age, sex, and education (n=48), African Americans had significantly higher WMH load (27% vs 4%, 2 =5.3, p=0.02). Conclusion: Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.