Lead Exposure and Alzheimer’s Disease Mortality Among US Adults: NHANES Analysis from 1988-2008

Abstract

AbstractObjectiveTo investigate the association between blood lead level (BLL) and Alzheimer’s disease (AD) mortality.DesignProspective cohort study.SettingUS National Health and Nutrition Examination Survey (NHANES) 1988-94 and 1999-2008.Participants21,308 subjects aged 40 years and over with a BLL ≥1.0 µg/dL.Main outcome measuresAD mortality from baseline until December 2019.ResultsAD was the underlying cause of death for 350 participants. In the fully adjusted model with a calendar effect variable, log-transformed BLL was inversely associated with AD mortality among all subjects (HR: 0.57 [95% CI, 0.46, 0.70]). A similar finding was evident when BLL was modeled as a categorical variable, with hazard ratios of 0.69 (95% CI: 0.54, 0.88), 0.56 (0.39, 0.80), 0.36 (0.19, 0.70), and 0.31 (0.14, 0.72) for 2.5-4.9 µg/dL, 5.0-7.4 µg/dL, 7.5-9.9 µg/dL, and ≥10 µg/dL, when compared to 1-2.4 µg/dL (p-trend < 0.0001). Restricted cubic spline analysis confirmed an inverse dose-response relationship between BLL and AD mortality.ConclusionsOur study suggests an inverse association between lead exposure and AD mortality among US adults; however, the results should be interpreted with caution due to the observational nature of the study.What is already known on this topicStudies investigating the association of blood lead and Alzheimer’s disease are rare.Prior publications reported increased risk of Alzheimer’s disease mortality with exposure to lead, however, due to potential biases in these prior studies, it was critical to reassess the association between blood lead and Alzheimer’s disease mortality.What this study addsIn contrast to much of the existing literature on dementia, the findings from this study suggest that lead exposure reduces the risk of Alzheimer’s disease mortality and likely mitigates the development of Alzheimer’s disease itself.Prospective studies focused on blood lead and its association with the development or progression of Alzheimer’s disease are necessary to confirm the results.