Disentangling the Impacts of Cadmium Exposure and Smoking Behavior on Age-Related Cognitive Decline in a Representative U.S. Sample

Abstract

Background: Cadmium is a toxic metal that has, in a sparse literature, been linked to age-related cognitive decline. We investigated cadmium exposure and cognitive function while considering confounding and modifying effects of tobacco use, given tobacco is a major source of cadmium exposure and is linked to cognitive decline.Methods: We included 2,069 adults age 60 years and older from the National Health and Nutrition Examination Survey (NHANES), 2011-2014, after excluding 262 with missing data, classifying active smokers by self-report or serum cotinine levels >10ng/mL. Cadmium levels in whole blood likely reflected prolonged exposure due to persistence in human tissues: mean=0.52μg/L (standard deviation=0.45μg/L). Cognitive performance was assessed concurrently with blood testing, via four neuropsychological tests: tapping memory, executive function, sustained attention, and working memory, which were standardized and combined to form a composite cognitive z-score mean z=0 (stdev 0.75). We used linear models to estimate change in cognitive function per 1-unit μg/L increase in cadmium, incorporating the NHANES MEC sampling weights.Results: Initial observations of worse cognitive performance with higher cadmium from unadjusted models, β= -0.17 (95% CI -0.24, -0.09), were highly attenuated after adjusting for gender, age, age^2, race/ethnicity, marital status, education level, and poverty income ratio: β= -0.08 (95% CI -0.14, -0.01). Additional adjustment for smoking status (active/former/never) and serum cotinine further attenuated this association: β= -0.05 (95% CI -0.13, 0.03). The cadmium-cognition association was not modified by smoking status; the p value on a likelihood ratio test of cadmium*smoking status=0.34.Conclusion: In contrast to prior studies, our findings suggest that cadmium is not related to cognitive decline, although our design was limited to a single cognitive measure rather than a trajectory of cognitive decline and may have been impacted by missing data. Studies that fail to account for tobacco exposure may over-estimate the neurodegenerative impacts of cadmium.