Loss, inflammation, and cognition: Understanding the lifecourse impact of early life parental disruption.

Social and structural determinants of health significantly impact well-being across the lifecourse and contribute to ethnoracial disparities in cognitive aging. Early-life exposure to parental disruption (i.e., death, divorce, or separation), which disproportionately affects ethnoracially diverse children, increases the risk of adverse brain health outcomes. Systemic inflammation, a key biological mechanism linking early stress to cognitive aging, affects neurocognitive pathways. However, little is known about how the relationship between parental disruption, inflammation, and cognition varies by ethnoracial group. This study examines the mediating role of systemic inflammation in the relationship between early-life parental disruption and late-life global cognition among non-Hispanic White (69.11 %), Black (16.45 %), and Hispanic (11.64 %) adults aged 55+ in the Health and Retirement Study (HRS). Data on systemic inflammation were obtained from the 2016 HRS Venous Blood Study, and early-life experiences from the 2015-2017 Life History Mail Survey. Using structural equation modeling (SEM), we constructed a latent variable of systemic inflammation based on Meier et al. (2023), incorporating CRP, IL-6, IL-10, IL-1RA, TNFR1, IGF-1, and the neutrophil-to-lymphocyte ratio. SEM with full information maximum likelihood (FIML) was used to address missing data and assess indirect effects. Inflammation was associated with lower cognition among non-Hispanic White and Hispanic participants, but not Black participants. Among non-Hispanic Whites, parental disruption was linked to higher inflammation, which in turn predicted lower cognitive performance. The pathway differed for Black participants, suggesting distinct psychosocial risk and resilience processes. Findings highlight the importance of lifecourse and culturally responsive approaches to addressing disparities in cognitive aging.