Investigating Biological Pathways Underpinning the Longitudinal Association Between Loneliness and Cognitive Impairment.

This article investigates whether specific biomarkers mediate the longitudinal relationship between loneliness and cognitive impairment (CI) in older adults, using data from the Health and Retirement Study (N = 7,037) over an eight-year period. Loneliness was measured by the 3-item University of California-Los Angeles (UCLA) loneliness scale, and cognitive status was assessed via the modified telephone interview for cognitive status (TICSm). The study examined five biomarkers—hemoglobin A1c (HbA1C), high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP), and cystatin C (CYSC)—as potential mediators. Results showed that while loneliness was initially associated with worse cognitive status and HbA1C partially mediated this relationship, all associations became nonsignificant after controlling for sociodemographic and health-related confounders, and none of the biomarkers consistently mediated the loneliness-CI link longitudinally. The findings highlight the importance of accounting for confounders and suggest that other factors, such as self-rated health and chronic disease burden, may better explain the association between loneliness and cognitive decline.