Psychosocial stress has been associated with impaired cognition and risk for neurodegenerative disease. However, the intermediate pathways underlying this relationship are not yet well understood. Chronic exposure to stress causes endocrine and immune dysregulation that can lead to heightened systemic inflammation. Moreover, chronic, low-grade inflammation has been linked to neurodegeneration, impaired neurogenesis and cognitive decline. Given the strength of the individual links between stress, inflammation and cognition, the current study tested the hypothesis that inflammatory biomarkers would mediate the relationship between perceived stress and executive functions.

Data from the Midlife in the United States Study (MIDUS) (N=863; Mean age= 52.72) provided measures of perceived psychological stress, inflammatory biomarkers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and executive functions. Structural equation modeling (SEM) was used to test for the mediating effect of inflammation on the relationship between perceived stress and executive functions. Exploratory analyses were conducted to investigate whether sex-differences were driving these relationships. Mediation analyses adjusted for age and history of smoking.

In the full sample of men and women, there was a significant indirect effect of perceived stress on executive functions through inflammation [ß=-0.021, z=-2.841, p=0.005]. Further examination revealed that this effect was present in women [B=-0.039, z=-2.680, p=0.007] but not men [ß=-0.003, z=-0.558, p=0.577]. While inflammation was negatively associated with executive functions in both men and women [ß=-0.126, z=-1.930, p=0.050; ß=-0.279, z=-0.558, p>0.001], pathways linking perceived stress to inflammation and executive functions were only significant in women [ß=0.014, z=-3.190, p=0.001; ß=-0.192, z=-3.355, p=0.001].

These findings suggest that inflammatory biomarkers are a viable pathway for explaining how experiencing stress can negatively affect executive functions. Results indicate that women may be particularly vulnerable to the inflammatory and cognitive consequences of stress. As such, psychosocial stress and associated inflammation may be important targets for improving cognitive health outcomes, particularly in women.