Dietary patterns, oxidative stress, and cognitive decline a multiple mediation analysis based on structural equation modeling

Objective: To examine the relationship between older adults diet-and-lifestyle oxidative balance score (Oxidative Balance Score, OBS) and cognitive function, and to investigate whether oxidative stress mediates that relationship. Methods: A total of 1,044 adults aged 60 years and older were included from the 20112014 National Health and Nutrition Examination Survey (NHANES). Cognitive function was assessed by four tests: the Immediate Recall Test (IRT), Delayed Recall Test (DIR), Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Weighted multivariable linear regression and restricted cubic spline (RCS) analyses evaluated the associations between OBS and cognitive outcomes. Mediation analysis using structural equation modeling (SEM) tested the indirect effects of oxidative-stress biomarkers on these associations. Results: OBS was positively associated with IRT, DIR, AFT, DSST, and overall cognitive function; the estimates (95% CI) were 5.83 (5.106.56), 0.38 (0.170.59), 15.37 (13.6417.09), 45.22 (40.9749.46), and 66.79 (61.4872.11), respectively. RCS analyses revealed approximately linear doseresponse relationships between OBS and IRT, DSST, and overall cognitive function. The 75th percentile and the highest quartile of scores on these three measures were also significantly associated with OBS. OBS directly and positively predicted overall cognitive ability, and was positively correlated with serum albumin and vitamin D levels while negatively correlated with uric acid. OBS may indirectly influence memory performance by modulating albumin, uric acid, and serum 25-hydroxyvitamin D [25(OH)D] levels. Conclusions: We propose a four-dimensional regulatory model diet lifestyle oxidative microenvironment cognitive function and provide evidence that multifactorial, synergistic antioxidant interventions have cumulative protective effects on cognition in older adults via a biomarker-network mediation mechanism. These findings support the development of personalized, oxidative-balance-based cognitive interventions and underscore the public-health value of whole-diet pattern adjustment combined with lifestyle optimization for preventing cognitive decline.