Abstract
INTRODUCTION: Growing evidence suggests lead exposure may increase dementia risk, but evidence from human studies is limited. We investigated associations between lead exposure and incident Alzheimer disease (AD) and all-cause dementia in a nationally-representative, prospective cohort. METHODS: We examined over 14,000 individuals with baseline measured blood lead and estimated patella and tibia lead from the National Health and Nutrition Examination Survey (NHANES)-III (1988-1994) and continuous NHANES (1999-2016), linked to Medicare and the National Death Index for incident AD and all-cause dementia, with up to 30 years of follow-up. Survey-weighted Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In continuous NHANES, estimated patella lead was positively associated with AD (HR=2.96, 95% CI: 1.37-6.39) and all-cause dementia (HR=2.15, 95% CI: 1.33-3.46), comparing quartile-4 vs. quartile-1. We observed weaker associations in NHANES-III. Blood lead showed no association. DISCUSSION: These findings suggest cumulative lead as a potential dementia risk factor.