Exposure to lead and incidence of Alzheimer's 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 prospective associations between lead exposure and incident Alzheimer's disease (AD) and all-cause dementia in nationally-representative US populations.

METHODS

Baseline measured blood lead and estimated patella and tibia lead from the National Health and Nutrition Examination Survey (NHANES)-III (1988-1994, blood n = 6,217, bone n = 5,865) and continuous NHANES (1999-2016, blood n = 8,038, bone n = 4,824) were 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 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.

HIGHLIGHTS: We examined Medicare-linked National Health and Nutrition Examination Survey (NHANES) on lead exposure and incident Alzheimer's disease (AD) and dementia. Lead exposure was assessed by blood lead and algorithm-estimated bone lead levels. High estimated patella lead was linked to increased all-cause dementia incidence. Dementia cases drop by 18% if all patella lead levels reduce to the 25th percentile. Cumulative lead exposure may raise dementia risk, highlighting its potential impact.