Association of conicity index with cognitive function: Evidence from a cross-sectional NHANES 2011–2014 study and Mendelian randomization analysis

Obesity has been implicated in cognitive decline; however, the influence of central adiposity across diverse body types remains unclear. This study employed NHANES 2011-2014 data and Mendelian randomization (MR) analyses to investigate the relationship between the conicity index (C-index), a novel anthropometric indicator of abdominal fat, and cognitive function. Weighted multivariate generalized linear regression was applied to assess associations between the C-index and cognitive function. Cognitive performance was measured using 4 standardized tests and a composite Z-score, with analyses stratified by sex. Additionally, 2-sample Mendelian randomization using genome-wide association study data evaluated causal effects of trunk and overall body fat on cognition, with reverse MR and sensitivity analyses performed to confirm robustness. A total of 2606 participants were analyzed. Weighted multivariate generalized linear regression indicated that, after adjusting for covariates, higher C-index values were significantly associated with poorer cognitive performance in the general population. Significant associations were observed for the immediate recall test (IRT), digit symbol substitution test (DSST), and overall cognitive Z-scores, with β coefficients (95% confidence interval [CI]) of -0.872 (-1.494, -0.251), -1.045 (-1.586, -0.503), and -0.693 (-1.195, -0.191), respectively. In sex-stratified analyses, higher C-index was significantly associated with DSST and overall Z-scores in men (β = -1.692, 95% CI: -2.488, -0.897; β = -0.852, -1.631, -0.073), whereas in women, associations were significant for immediate recall test, DSST, and overall Z-scores (β = -0.897, -1.667, -0.127; β = -0.716, -1.426, -0.005; β = -0.663, -1.311, -0.016). MR supported causal effects of trunk fat (inverse-variance weighted odds ratio = 0.88, 95% CI: 0.82-0.95) and overall body fat (inverse-variance weighted odds ratio = 0.85, 95% CI: 0.78-0.92) on cognition, with no evidence of reverse causality. Elevated C-index levels are associated with poorer cognitive performance, indicating that higher central adiposity may adversely impact cognitive function.