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

Abstract

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%, Χ 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.

Exploring the combined effects of sleep apnea and APOE-e4 on biomarkers of Alzheimer’s disease

“…While our results do demonstrate a higher proportion of Black/African Americans having at least one APOE-e4 allele (44.4% vs. 40.4%), they also demonstrate that the presence of an APOE-e4 allele was associated with WMH and Hippocampal volume, but not cognitive status in Black/African Americans in our sample. These results add to the literature that posits differential associations with WMH being the driver of disparate WMH burden seen by race ( Seixas et al, 2021 ), especially since no significant differences were seen in WMH burden across race in this sample. However, given the fact that we did not conduct analyses subdivided by cognitive status, caution must be taken with inferences related to the results surrounding cognitive status.…”

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities

“…246 In another study, obesity was found to significantly increase the risk of WMH in African Americans. 247 These findings indicate that obesity is associated with LA severity and that it could be involved in the pathogenesis of LA. Another recent study showed that visceral obesity contributed to a higher DWMH/PVWMH ratio through elevated levels of the pro-inflammatory cytokine interleukin-6, independent of age and sex, thus providing insights into the possible inflammatory mechanisms underlying DWMLs, 245 although future studies are required to confirm this hypothesis at the molecular level and using imaging assessment and animal models.…”

“…69,125,245 Recently, the association between obesity and LA was shown to depend on sex and race. 246,247 In one study, there were significant differences between men and women in terms of the association between BMI and DWMH; moreover, only male sex interacted with higher BMI to result in increased DWMH volume. 246 In another study, obesity was found to significantly increase the risk of WMH in African Americans.…”

White Matter Hyperintensities in Young Patients from a Neurological Outpatient Clinic: Prevalence, Risk Factors, and Correlation with Enlarged Perivascular Spaces

“…The prevalence of WMH differs between populations, wherein WMH frequently observed in older populations. Seixas et al demonstrated that the prevalence of WMH was 95.8% among healthy individuals (age: 65.1 ± 8.2 years) [ 10 ]. Another study reported that the prevalence of WMH was 56% in healthy individuals (age: 16–78 years) [ 11 ].…”