Abstract

Introduction: We evaluated the association of a cigarette-smoking biomarker with cognitive function, and tested whether smoking acts synergistically with hypertension and diabetes to influence cognition. Methods: We performed a cross-sectional analysis of nationally representative data from the US National Health and Nutrition Examination Survey. From 2011-2014, participants ≥60 years old were given 4 standardized cognitive tests by trained examiners: immediate word recall, delayed word recall, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST) - a multidomain cognitive test. Participants also had 3 consecutive standardized blood pressure measurements and hemoglobin A1c and serum cotinine tests, the latter an accurate biomarker of cigarette smoking/exposure. We used linear regression to evaluate the association of cotinine with cognitive performance. Where an association was found, interaction term testing evaluated effect modification by systolic blood pressure and hemoglobin A1c as continuous measures, and hypertension and diabetes as categorical variables. Models were adjusted for demographics, socioeconomic factors, education, cardiovascular risk factors/disease, alcohol use, and depression. Results: The mean age of 3,244 participants was 69 years and 54% were women. Self-reported current smoking was present in 23%, 77% had hypertension, and 24% had diabetes. In adjusted linear regression models, higher serum cotinine levels were associated with worse performance on the DSST (β, -0.02; 95% CI, -0.03, -0.01; P=0.001), and non-significantly on the AFT (β, -0.003; 95% CI, -0.006, 0.0003; P=0.07), but not immediate or delayed recall. For the DSST, effect modification by systolic blood pressure (P=0.14) and hemoglobin A1c (P=0.39) was not observed. There was also no evidence of effect modification when testing interactions for hypertension and diabetes. Conclusions: Higher levels of a smoking biomarker were associated with worse performance on a multidomain cognitive test at the population level, regardless of hypertension or diabetes. These data demonstrate the detrimental impact of smoking on cognition and underscore the broad importance of promoting smoking cessation to preserve cognitive health.

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