The Mediating Role of Systemic Inflammation and Moderating Role of Racialization in Disparities in Incident Dementia: A Decomposition Analysis

César Higgins Tejera, Erin B. Ware, Margaret T. Hicken, Lindsay C. Kobayashi, Herong Wang, Freida Blostein, Matthew Zawistowski, Bhramar Mukherjee, Kelly M. Bakulski

Background: Exposure to systemic racism is linked to increased dementia burden. To assess systemic inflammation as a potential pathway linking exposure to racism and dementia disparities, we investigated the mediating role of C-reactive protein (CRP), a systemic inflammation marker, and the moderating role of the racialization process in incident dementia. Methods: In the US Health and Retirement Study (n=6,908), serum CRP was measured at baseline (2006, 2008 waves). Incident dementia was classified by cognitive tests over a six-year follow-up. Self-reported racialized categories were a proxy for exposure to the racialization process. We decomposed racialized disparities in dementia incidence (non-Hispanic Black and/or Hispanic vs. non-Hispanic White) into 1) the mediated effect of CRP, 2) the moderated portion attributable to the interaction between racialized group membership and CRP, and 3) the controlled direct effect (other pathways through which racism operates). Results:: The 6-year cumulative incidence of dementia was 12%. Among minoritized participants (i.e., non-Hispanic Black and/or Hispanic), high CRP levels (> 75th percentile or 4.73g/mL) was associated with 1.26 (95%CI: 0.98, 1.62) times greater risk of incident dementia than low CRP (<4.73g/mL). Decomposition analysis comparing minoritized versus non-Hispanic White participants showed that the mediating effect of CRP accounted for 3% (95% CI: 0%, 6%) of the racial disparity, while the interaction effect between minoritized group status and high CRP accounted for 14% (95% CI: 1%, 27%) of the disparity. Findings were robust to potential violations of causal mediation assumptions. Conclusions: Minoritized group membership modifies the relationship between systemic inflammation and incident dementia.