Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study.

White matter hyperintensities or lesions (WMLs) increase the risk for cognitive impairment and dementia. Cardiometabolic factors (e.g., excess adiposity) and markers of systemic inflammation relate to greater WML volume, but few studies have examined whether specific compartments of adipose tissue (e.g., visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT)) relative to total body adiposity (TBA) differentially relate to WML volume or whether these patterns could be statistically mediated by inflammation. We examined associations between markers of low-grade systemic inflammation and compartments of adipose tissue relative to total body adiposity (rVAT or rASAT respectively), measured by dual-energy x-ray absorptiometry (DXA), and WML volume. We hypothesized that higher rVAT and not rASAT would be associated with greater WML volume, and that this association would be statistically mediated by concentrations of inflammatory cytokines. We used baseline data (n = 648) from the multisite study "Investigating Gains in Neurocognition in an Intervention Trial of Exercise" (IGNITE; mean age = 69.9 ± 3.8 years, 70.5 % females). IL-6, IL-1RA, and TNF-α were included as markers of systemic inflammation and age, sex, years of education, hypertension status, and study site were included as covariates. Our hypotheses were partially supported such that the relationship between rVAT and WMLs, as well as between rASAT and WMLs, were statistically mediated by IL-6 and TNF-α. These findings suggest that both higher rVAT and rASAT, are associated with higher WML burden through an elevated inflammatory state. These results set a testable mechanistic pathway for future longitudinal and intervention studies examining whether managing low-grade systemic inflammation and intentional weight loss would be beneficial for supporting brain health in older adults.