Opposing effects of uric acid and triglycerides on cognitive decline cancel within a metabolic oxidative composite: Longitudinal evidence from CHARLS and cross-sectional replication in NHANES

Background Composite metabolic-oxidative scores have shown inconsistent associations with cognitive outcomes, yet whether their components move in the same direction remains unexamined. Objective To test whether Metabolic Oxidative Risk Score (MORS) tracks cognitive change, and to decompose MORS to assess whether component effects on cognitive slope are concordant or opposing. Methods We constructed a four-component MORS (uric acid, triglycerides, fasting glucose, reverse-scored HDL; range 4–20) and examined its association with cognitive change across four waves (2011–2018) in CHARLS (N = 7,300, age ≥ 45 years) using linear mixed models. Equivalence testing distinguished null findings from insufficient power. Components were decomposed individually and simultaneously. Cross-sectional triangulation used NHANES 2011–2014 (N = 1,340, age ≥ 60 years). Results The adjusted MORS × time interaction was β = −0.00046 SD/year (95% CI −0.00185 to 0.00093; p = 0.516); equivalence testing rejected any clinically meaningful effect (p = 0.0002). Component decomposition revealed opposing effects: higher uric acid predicted steeper decline (β = −0.0055; p = 0.003) while higher triglycerides predicted attenuated decline (β = + 0.0042; p = 0.045), with near-perfect cancellation at the composite level. In NHANES, the MORS–cognition association reversed sign after socioeconomic adjustment and showed a significant non-linear association (p = 6 × 10 −4 ); leave-one-out analysis identified uric acid as the dominant signal carrier. Conclusions An equal-weight metabolic-oxidative composite does not track cognitive decline because its components exert opposing effects that cancel. Uric acid emerges as an independent, potentially modifiable risk factor with implications for Alzheimer's disease prevention research.