The Mediating Role of Systemic Inflammation in the Differences in Cognitive Disease Incidence and the Moderating Role of Racialization

This study examines the link between systemic racism and the increased burden of cognitive disease. Researchers investigated the mediating role of C-reactive protein (CRP) as a marker of systemic inflammation in the relationship between exposure to racism and differences in cognitive disease incidence, as well as the moderating role of the racialization process. Through the Health and Retirement Study in the United States (sample of 6,908 people), researchers measured serum CRP at baseline (2006, 2008) and classified cognitive diseases through cognitive tests in a six-year follow-up. Self-reported racial categories were used as proxies for exposure to racialization processes. The study decomposed the differences in cognitive disease incidence between non-Hispanic Blacks and/or Hispanics and non-Hispanic Whites, including 1) the mediating effect of CRP, 2) the moderating part attributed to the interaction between racial group identity and CRP, and 3) controlling for direct effects (other pathways of the effect of racism).

Results showed that the six-year incidence rate was 12%. Among participants viewed as minorities (i.e., non-Hispanic Blacks and/or Hispanics), high CRP levels (≥75th percentile or 4.73 μg/ml) were associated with a 1.26 times increased risk of cognitive disease compared to low CRP levels (< 4.73 μg/ml) (95% CI: 0.98, 1.62). Decomposition analysis indicated that the mediating effect of CRP explained 3% of the racial differences (95% CI: 0%, 6%), while the interaction effect between racial group identity and high CRP explained 14% of the differences (95% CI: 1%, 27%). The results were robust to potential violations of the hypothesized causal mediation assumption.

The conclusions suggest that being viewed as a minority changes the relationship between systemic inflammation and cognitive disease incidence. Cognitive disease is a leading cause of morbidity and mortality in the United States, a debilitating condition requiring care and support for daily life activities. Due to demographic changes in the aging population, lack of early diagnosis, and definitive treatment, the burden of cognitive disease is expected to increase. In the United States, non-Hispanic Blacks and Hispanic Americans are more likely to develop cognitive diseases than their White counterparts. The growing burden of cognitive disease will disproportionately affect populations already vulnerable due to increased risks of other chronic diseases.

This study was conducted by César Higgins Tejera, Erin B. Ware, Margaret T. Hicken, Lindsay C. Kobayashi, Herong Wang, Freida Blostein, Matthew Zawistowski, Bhramar Mukherjee, and Kelly M. Bakulski, and is affiliated with the following institutions: University of Michigan School of Public Health, Johns Hopkins University Department of Neurology, Division of Neuroimmunology and Neurological Infections, University of Michigan Institute for Social Research, and Vanderbilt University. The paper was published in the journal Communications Medicine, DOI: 10.1038/s43856-024-00569-w, in 2024.

The study detailed that CRP might capture the physiological response to racialization and its continuous effect on cognitive aging. The co-localization of local glial cells and pro-inflammatory cytokines in amyloid-β plaques indicates that neuroinflammation plays a critical role in the pathogenesis of dementia. Observational epidemiological studies suggest a link between systemic inflammation and the onset of dementia. The study also indicated that CRP might be an important mediator explaining racial differences in cognitive aging.

This study examined the mediating role of systemic inflammation and the moderating effect of racialized groups on differences in cognitive disease incidence. The research provides empirical evidence for understanding how structural racism affects health disparities and suggests that public health agencies understand the association between structural racism and systemic inflammation, with the aim of reducing the gaps in adverse cognitive outcomes among racial groups.