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

ObjectiveTo investigate the association between blood lead level (BLL) and Alzheimers 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 [&ge;]1.0 {micro}g/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 {micro}g/dL, 5.0-7.4 {micro}g/dL, 7.5-9.9 {micro}g/dL, and [&ge;]10 {micro}g/dL, when compared to 1-2.4 {micro}g/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 topicO_LIStudies investigating the association of blood lead and Alzheimers disease are rare. C_LIO_LIPrior publications reported increased risk of Alzheimers 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 Alzheimers disease mortality. C_LI What this study addsO_LIIn contrast to much of the existing literature on dementia, the findings from this study suggest that lead exposure reduces the risk of Alzheimers disease mortality and likely mitigates the development of Alzheimers disease itself. C_LIO_LIProspective studies focused on blood lead and its association with the development or progression of Alzheimers disease are necessary to confirm the results. C_LI