Combined Influence of Depressive Symptoms and Estimated Glomerular Filtration Rate on Cognition Decline in US Adults

Background Cognitive decline is common in older adults and may be influenced by both depressive symptoms and kidney function. Methods We analyzed 2650 participants aged ≥ 60 years from NHANES 2011–2014. Depressive symptoms were defined as PHQ‐9 ≥ 10, and eGFR was calculated using the CKD‐EPI equation. Cognitive decline was defined as the lowest quartile of a composite score from CERAD, AFT, and DSST tests. Weighted logistic regression, restricted cubic spline, and mediation analyses were applied. Results Depressive symptoms (OR = 3.14, 95% CI: 1.91–5.19) and reduced eGFR < 60 mL/min/1.73 m 2 (OR = 2.13, 95% CI: 1.25–3.61) were independently associated with a higher risk of cognitive decline. Participants with both depressive symptoms and low eGFR had the greatest risk (OR = 11.74, 95% CI: 4.02–34.28). Nonlinear analysis showed an L‐shaped association between eGFR and cognition, and mediation analysis suggested depressive symptoms accounted for 15% of the effect of eGFR on cognition. Sex‐stratified results indicated stronger combined effects in females. Conclusions Both depressive symptoms and reduced eGFR are independent risk factors for cognitive decline, and their coexistence markedly amplifies risk, particularly in females. These findings highlight the importance of integrated screening and intervention for mental and renal health in older adults.