Sex differences in the mediating role of chronic inflammation on the association between social isolation and cognitive functioning among older adults in the United States

Previous research has reported the association between social isolation and cognitive impairment. However, biological mechanisms underlying this association are understudied. It is also unclear whether there are sex differences in these biological mechanisms.To examine whether chronic inflammation biomarkers are potential mediators of the association between social isolation and cognitive functioning among older men and women.Data were the National Health and Nutrition Examination Survey 1999-2002. A total of 2535 older adults aged 60 and older were included. Chronic inflammation was measured by C-reactive protein (CRP), plasma fibrinogen, and serum albumin. Cognitive functioning was assessed by the Digit Symbol Substitution Test (DSST). Social isolation was defined using a 4-point composite index of items pertaining to the strength of social network and support. Linear regression models and formal mediation analysis were applied.Social isolation was associated with lower DSST scores [β (SE) = -2.445 (1.180), p < 0.01 for men; β (SE) = -5.478 (1.167), p < 0.001 for women]. For older men, social isolation was associated with higher levels of CRP (β [SE] = 0.226 (0.110), p < 0.05) and fibrinogen (β [SE] = 0.058 (0.026), p < 0.05). In mediation analyses, among older men, CRP mediated 6.1% and fibrinogen mediated 12.0% of the association of social isolation with DSST.Social isolation was associated with poorer cognitive functioning partially via heightened inflammatory responses in older men. Defining these associations' mechanisms in sex-specific contexts could inform preventive and therapeutic strategies for cognitive impairment in older adults.