Associations between immunosenescence and domain-specific cognition in the Health and Retirement Study Harmonized Cognitive Assessment Protocol.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) pose a critical challenge for the aging U.S. population, yet many biological pathways remain unclear. Recent work has focused on whether peripheral immunosenescence contributes to cognitive aging. Using the Health and Retirement Study (HRS), we examined associations between peripheral immunosenescence and domain-specific cognitive function.

RESULTS: Immune function was associated with general and domain-specific cognition, with variation by sex and immune marker. The CD4 + EMRA:Naïve T Cell Ratio, CD4 + Naïve:CD8 + EMRA Ratio, and CMV IgG showed the most consistent associations, particularly with general and executive function. A one-SD increase in CMV IgG was associated with 0.06 SD lower executive function (95% CI: -0.07, -0.05), persisting after adjustment for confounders.

CONCLUSIONS: Associations with peripheral immune markers suggest a potential role for peripheral immunosenescence in cognitive aging. The immune system may be an early contributor to cognitive vulnerability, underscoring the need to integrate immune aging into ADRD research.