Abstract

BACKGROUND AND AIM: Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not been tested for association with cognition in an environment-wide association framework. METHODS: In the US National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants 60 years of age and older. Concentrations of environmental chemicals were measured in blood or urine. Chemicals with at least 50% of measures greater than the limit of detection were included (nchemicals=124, nclasses=16). We tested for differences in cognition by natural log transformed concentration of each chemical using parallel multivariable linear regression models accounting for age, sex, race/ethnicity, and educational attainment. We calculated false discovery rates (FDR). RESULTS:Participants with complete cognition/demographic measures and at least one chemical measure (n=5,670) were mean age 70.3 years, 51% female, 43.7% college educated, and 53.2% non-Hispanic White. The mean DSST score was 43.6 (18.1 standard deviation) and 24.2% were cognitively impaired (DSST28). In adjusted analyses, 75% higher lipid adjusted blood concentration of the pesticide DDT was associated with 1.4 points lower DSST score (95% Confidence interval (CI):-2.1,-0.7, FDR:0.0001). Similarly, 75% higher heptachlor concentration was associated with 0.9 points lower DSST score (95%CI:-1.6,-0.1, FDR:0.02). For metals, we observed 75% higher blood cadmium levels were associated with 0.7 points lower DSST score (95%CI:-1.1,-0.4, FDR:5*10-5) and 75% higher blood lead levels were associated with 0.6 points lower DSST score (95%CI:-0.9,-0.2, FRD:0.002). Among perfluoroalkyl substances, 75% higher urinary concentration of perfluoroundecanoic acid was associated with 0.5 points lower DSST score (95%CI:-1.0,0.07, FDR: 0.09). CONCLUSIONS:Exposure to environmental chemicals, particularly pesticides and metals, may be modifiable factors for reduced cognition among older adults. KEYWORDS: cognition, exposome, environment-wide association study, dementia

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