Links between inflammation and immune functioning with cognitive status among older Americans in the Health and...

Elevated inflammation and poor immune functioning are tied to worse cognitive health. Both processes are fundamental to aging and are strongly implicated in the development of age-related health outcomes, including cognitive status. However, results from prior studies evaluating links between indicators of inflammation and immune function and cognitive impairment have been inconsistent due to biomarker selection, sample selection, and cognitive outcome. Using the Health and Retirement Study (HRS), a nationally representative study of older adults in the United States, we assessed how indicators of inflammation (neutrophil-lymphocyte ratio (NLR), albumin, CRP, IL6, IL10, IL-1Ra, sTNFR1, and TGFβ1) and immune functioning (CMV, CD4⁺ T_N/T_M, and CD8⁺ T_N/T_M) are associated with cognitive status. First, to examine the association between each biomarker and cognitive status, we tested whether markers of inflammation and immune functioning varied across cognitive status categories. We found that dementia and cognitive impairment without dementia (CIND) were associated with elevated inflammation and poorer immune functioning across biomarkers except for CD4⁺ T_N/T_M. Next, we estimated multinomial logistic regression models to assess which biomarkers would continue to be associated with dementia and CIND, net of each other. In these models, albumin, cytokines, CMV, CD4⁺ T_N/T_M, and CD8⁺ T_N/T_M are associated with cognitive status. Because poor immune functioning and increased inflammation are associated with cognitive impairment, improving immune functioning and reducing inflammation may provide a mechanism for reducing ADRD risk in the population.