Exposure to Lead and Incidence of Alzheimer Disease and All-Cause Dementia in the United States

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.

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).

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.

These findings suggest cumulative lead as a potential dementia risk factor. Competing Interest Statement The authors have declared no competing interest. Funding Statement This research was supported by the National Institute on Aging (R01 AG070897, K01 AG084821, P30 AG072931) and the National Institute of Environmental Health Sciences (P30 ES017885). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the University of Michigan approved this work (HUM00194918). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Sharing Statement NHANES datasets are publicly available at https://www.n.cdc.gov/nchs/nhanes. Bone lead prediction models are publicly available at https://github.com/XinWangUmich/Bone-Lead-Prediction-Models. Restricted-use linked Medicare and National Death Index datasets must be analyzed in Federal Statistical Research Data Centers and require an application process to access.