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. 2019 May;3(3):e045.
doi: 10.1097/EE9.0000000000000045. Epub 2019 Jun 12.

Association between blood lead level and subsequent Alzheimer's disease mortality

Christelene Jack Horton  1 , Hsin-Yi Weng  2 , Ellen M Wells  1
Affiliations

Association between blood lead level and subsequent Alzheimer's disease mortality

Christelene Jack Horton et al. Environ Epidemiol. 2019 May.

Abstract

Background: Previous studies suggest that cumulative lead exposure is associated with cognitive decline, but its relation with Alzheimer's disease (AD) remains unclear. Therefore, this study investigated the longitudinal association between blood lead level (BLL) and AD mortality.

Methods: This study included 8,080 elders (60 years or older) with BLL data from the 1999 to 2008 US National Health and Nutrition Examination Survey. Mortality was determined from linked 1999-2014 National Death Index data. A causal diagram presented causal assumptions and identified a sufficient set of confounders: age, sex, poverty, race/ethnicity, and smoking. Cox proportional hazard models were used to determine the association between BLL and subsequent AD mortality. Impacts of competing risks and design effect were also assessed. Adjusted hazard rate ratio (HRR) and 95% confidence interval (CI) were reported.

Results: Follow-up ranged from <1 to 152 months (median, 74). Eighty-one participants died from AD over 632,075 total person-months at risk. An increase in BLL was associated with an increase in AD mortality after adjusting for identified confounders. We estimated that those with BLL of 1.5 and 5 μg/dl had 1.2 (95% CI = 0.70, 2.1) and 1.4 (95% CI = 0.54, 3.8) times the rate of AD mortality compared to those with BLL of 0.3 μg/dl, respectively, after accounting for competing risks. Adjusted HRRs were 1.5 (95% CI = 0.81, 2.9) and 2.1 (95% CI = 0.70, 6.3), respectively, after considering design effect.

Conclusions: This longitudinal study demonstrated a positive, albeit not statistically significant, association between BLL and AD mortality after adjustment for competing risks or design effect.

Keywords: Alzheimer's disease; Competing risk; Lead; Mortality; National Health and Nutrition Examination Survey.

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Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article.

Figures

Figure 1.
Figure 1.
Study sample flowchart.
Figure 2.
Figure 2.
Causal diagram presenting the causal assumptions among study variables in assessing the association between blood lead and Alzheimer’s disease mortality. Dashed line indicates proposed association between BLL and AD mortality. BMI indicates body mass index.
Figure 3.
Figure 3.
HRR for Alzheimer’s disease mortality by BLL, including lower 95% confidence interval. Estimates are derived from different Cox regression models incorporating either design effect or competing risks. Null line represents HRR = 1. LCI indicates lower 95% confidence interval.
See this image and copyright information in PMC

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