Exposome-wide association study of cognitive function in US older adults using the NHANES data

Abstract Neurodegenerative diseases pose increasing challenges to global aging populations. Cognitive decline in older adults is an initial indicator of neurodegenerative diseases, yet comprehensive research on environmental chemical exposures related to cognitive decline is limited. This study uses Exposome-Wide Association Study (ExWAS) framework to investigate associations of environmental chemicals with cognitive function in individuals aged ≥60 years. We used the Digit Symbol Substitution Test (DSST) scores and chemical biomarker data of the US National Health and Nutrition Examination Survey (NHANES) spanning four cycles (1999-2000, 2001-2002, 2011-2012, 2013-2014). We conducted multiple survey-weighted regression to identify biomarkers associated with DSST scores, Bayesian weighted quantile sum regression to estimate odds ratio (OR) of cognitive decline from multiple exposures to the identified biomarkers, and correlation network analyses to examine relationships among possible important biomarkers and cognitive decline. After correction for multiple comparisons, among 229 biomarkers having a ≥10% detection rate, 40 were associated with DSST scores (q-value <0.05). When assessing the effects of chemical mixtures on cognitive decline, no association between mixtures of chemicals and DSST scores was observed. Correlation network showed that cognitive decline is directly related with age and education level and identified that thiocyanate, m-/p-xylene, triclosan, benzophenone-3 and diphenyl phosphate were weakly related to cognitive function. In conclusion, leveraging the ExWAS framework enables us to identify chemical biomarkers that were not previously discovered from traditional approaches of examining a small number of chemicals at a time. While our findings provide foundation for further research, longitudinal studies are warranted to elucidate causal relationships.