Sex differences in the association between energy-adjusted dietary inflammatory index and cognitive function in older adults.

INTRODUCTION: Diet-induced inflammation may influence cognitive health in older adults, yet sex-specific associations across distinct cognitive domains remain unclear. METHODS: Using weighted multivariable regression, weighted restricted cubic splines, and weighted risk group analyses (energy-adjusted Dietary Inflammatory Index [E-DII] lowest quartiles), we assessed E-DII associations with four cognitive tests (Animal Fluency Test [AFT], Digit Symbol Substitution Test [DSST], Delayed Recall Test [DRT], and Immediate Recall Test [IRT]) in older adults. All analyses included sex stratification or sex interaction. Weighted mediation analysis by 15 blood biochemical markers was explored. RESULTS: In older males, higher ln(E-DII) was linked to poorer AFT and DSST performance and increased low cognition risk in AFT, DSST, and DRT; no associations were found in older females. Gamma-glutamyl transferase mediated the ln(E-DII)-DSST association in older males. DISCUSSION: These sex-specific links highlight the need for personalized dietary strategies to protect cognitive health in aging populations. HIGHLIGHTS: E-DII exhibits sex-specific associations with multiple cognitive domains in older adults. Higher ln(E-DII) is linked to poorer verbal fluency (AFT), processing speed (DSST), and increased low cognition risk (AFT, DSST, and DRT) in older males, but not in older females. Gamma-glutamyl transferase mediates the association between ln(E-DII) and DSST performance specifically in older males. Findings support the development of personalized, sex-specific dietary strategies to preserve cognitive health in aging populations.