Investigating the Association between Blood Lead Levels and Alzheimer's Disease Mortality Using NHANES 1999-2008

Abstract

Toxicological and epidemiological studies suggest that there is an association between lead (Pb) exposure and Alzheimer’s disease (AD); however, few studies have explored Pb and AD mortality. The main objective of this study was to investigate the longitudinal association between blood Pb with subsequent AD mortality. Data from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) and 1999-2014 linked National Death Index files were used for this longitudinal analysis. Analyses included 8084 adults aged ≥ 60 years with blood Pb data at the NHANES exam. Cox proportional hazards regression was used to estimate the hazard ratio of AD mortality by blood Pb tertile, adjusting for age, gender, income, race/ethnicity and smoking status. At the time of the NHANES survey, geometric mean blood Pb was 2.45 (95% confidence interval (CI): 2.39, 2.53). N=2227 participants died during follow-up; N=81 died from AD, which is a proportionate mortality of 3.89% (95% CI: 3.00, 5.00). Tertiles of blood Pb were < 1.50 µg/dL; 1.50 to 3.00 µg/dL; and > 3.00 µ/dL. In adjusted models using the lowest blood Pb tertile as the referent, participants in the second and third blood Pb tertile had 1.61 (95% CI: 0.84, 3.11) and 1.74 (95% CI: 0.86, 3.52) times the risk of AD mortality, respectively. A limitation of this analysis is that the true burden of AD may not be well represented by mortality, as those with AD may die from other causes. However, this study has several strengths: it is longitudinal, uses a large sample, and is representative of the United States population. Although it was not statistically significant, results from this analysis suggest that there is an association of increased Pb with AD mortality. Further research in this area is recommended.