Longitudinal Stability and Cross‐Sectional Correlates: Cognition, Stress, and Inflammation in Midlife

To investigate longitudinal relationships among psychological stress, inflammation biomarkers, and cognitive function over a 9-year period using data from the Midlife in the United States (MIDUS) study. Structural Equation Modeling (SEM) was conducted on MIDUS Wave 2 data (M2, N = 790), incorporating biomarkers of stress (cortisol, norepinephrine, epinephrine, dopamine), inflammation (interleukin-6, C-reactive protein, fibrinogen, soluble ICAM-1), and cognition (episodic memory, executive function), with follow-up cognitive outcomes from MIDUS Wave 3 (M3). Confirmatory Factor Analysis (CFA) assessed measurement validity, and key SEM assumptions were tested. CFA indicated acceptable model fit. SEM revealed significant cross-sectional associations among stress, inflammation, and cognitive variables at baseline. Baseline cognitive function strongly predicted follow-up cognition 9 years later, indicating high longitudinal stability. However, stress and inflammation biomarkers from M2 did not directly predict M3 cognition. Indirect effects emerged: M2 cognition influenced both M3 executive function and episodic memory through M3 global cognition. Multi-group analysis showed no gender-based differences in model paths. Stress and inflammation biomarkers were associated with cognition cross-sectionally but showed no direct long-term effects. Findings highlight the relative stability and predictive continuity of midlife cognition rather than substantial mean-level change, underscoring midlife as a critical window for sustaining cognitive health.