Association between serum cotinine levels and cognitive function in Americans aged 60 and older: A cross-sectional study

Cognitive decline poses a major public health burden on the aging population, necessitating the identification of modifiable risk factors. Cotinine, a key nicotine metabolite and an established biomarker of tobacco exposure, has demonstrated biologically plausible associations with cognitive function. This study examined the association between serum cotinine levels and cognitive function in US adults aged ≥60 years. We conducted a cross-sectional study including 2781 participants aged ≥60 years, using data from the United States National Health and Nutrition Examination Survey from 2011 to 2014. Sampling weights were applied in all analyses to account for the complex survey design and ensure national representativeness. We used multivariable linear regression supplemented by stratified analyses, sensitivity analyses, and restricted cubic splines to model nonlinear associations. Multivariable-adjusted analyses showed a significant inverse association between serum cotinine levels and cognitive function (β = −0.85, 95% confidence interval: −1.62 to −0.08, P = .034). Subgroup analyses consistently demonstrated this inverse association across strata (all P for interaction > .05). Sensitivity analyses supported the robustness of these findings. Curve fitting revealed an L-shaped relationship (inflection point: log 2 cotinine = −0.16; 95% confidence interval: −0.30 to −0.03, P for nonlinearity = .022), with a significant inverse association observed below this threshold ( P = .017), whereas the association plateaued above the threshold ( P = .063), suggesting a potential threshold-dependent association between serum cotinine and cognitive function. This cross-sectional study found a significant inverse association between serum cotinine levels and cognitive function in older adults in the United States, which was observed as an L-shaped relationship with a threshold of log 2 cotinine = −0.16. These findings contribute to evidence on tobacco exposure and cognitive outcomes in aging populations.