Nicotine exposure and mild cognitive impairment in the elderly：A mixtures approach

Background: The relationship between nicotine exposure and cognitive impairment remains controversial. Evidence for combined exposure to its metabolites is also inconclusive. The extensive exposure of metabolites represents the exposure level of nicotine to a certain extent. Therefore, it is essential to explore the comprehensive association between nicotine metabolites and mild cognitive impairment. Methods: This cross-sectional study measured eight nicotine metabolites in the urine of older adults。 Associations between nicotine metabolites were assessed using logistic regression models. An integrated exposure model was then applied for a comprehensive assessment of metabolites, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQS), and grouped weighted quantile sums (GWQS). Results: The complete population logistic regression results indicated that CNO was negatively associated with mild cognitive impairment. In contrast, Cot and OHCotGluc showed a trend toward a positive association. Logistic regression results excluding the smoking population showed that OHCotGluc, NNO, and Cot were significantly positively associated with MCI. CNO and OHCotGluc were negatively associated with MCI. In the WQS, the total population had a positive association between combined exposure and mild cognitive impairment (OR: 1.15; 95% CI: 1.04–1.26). Metabolites were grouped for smoking and non-smoking populations based on the BKMR and logistic regression cues. The GWQS results showed an OR of 2.08 (95% CI:1.55,2.83) for the OHCotGluc (43.6%) dominated metabolite group and 0.78 (95% CI:0.613,0.98) for the CNO (55.92%) dominated metabolite group in the non-smoking population. An OR of 2.61 (95% CI:1.42,5.10) for the metabolite group dominated by CotGluc (35.86%) and 0.38 (95% CI:0.19,0.69) for the metabolite group dominated by NNO (47.4%) was found in the smoking population. Significance The association of nicotine metabolites with MCI was analyzed using combined exposure and single-factor exposure models. Provides new clues to the cognitive impact of nicotine exposure in older adults.