<p>This dissertation examines lead exposure and effects across the lifespan among vulnerable populations. The vulnerable population that this dissertation focuses on are the elderly, newcomers to the US, which represents immigrants, as well as adolescents and women of childbearing age. The first chapter gives an introduction and highlights the history of lead as it relates to environmental and occupational exposure having deleterious effects on the human system. The second chapter highlights the association between blood lead level and subsequent Alzheimer’s disease (AD) mortality in those 65 years and older. Chapter 3 looks at whether length of time in the United States is a predictor of adolescent and adult blood lead levels. The fourth chapter assesses whether early life lead exposure is associated with AD mortality later in life. Adaptations of Chapter 2 and Chapter 3 of this dissertation have been submitted for publication.</p><p>Chapter 2 presents a longitudinal study of 8080 elders (≥60 years) with BLL data from the 1999-2008 National Health and Nutrition Examination Survey, where mortality was determined from linked 1999-2014 National Death Index data. In this study, 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 showed that those with BLL of 1.5 μg/dL 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. This longitudinal study demonstrated a positive, albeit statistically non-significant association between BLL and AD mortality, after adjustment for competing risks or design effect.</p><p>Chapter 3 included cross-sectional 1580 women of childbearing age (15-45 years) and 5933 men and women (≥15 years) from the 2013-2016 United States National Health and Nutrition Examination Survey. Linear regression models adjusted for race/ethnicity, education, blood cotinine, age, sex (as appropriate) and accounted for complex survey design. Results showed that women of childbearing age who have lived 0-4 years in the US have, on average, a 43% (95% confidence interval (CI): 31%, 56%) higher BPb compared to women born in the US. Corresponding results for all adults and adolescents was 40% (95% CI: 28%, 51%). Similar, statistically significant, results were observed for other time periods (5-9 years, 10-19 years, and ≥20 years); the magnitude of the association decreased with increasing time in the US. Higher BPb was also significantly associated with Asian (vs. white), lower education, higher age, and male (vs. female).</p><p>Chapter 4 is an ecologic study utilizing data from the United States Census Bureau and American Fact Finder. This ecologic study uses publicly available data from the 1930s US census and the Centers for Disease Control and Prevention to compare estimated historic lead exposure with AD mortality rates among US states and Indiana counties. Occupations were assigned a numeric weight based on the likelihood of lead exposure. The proportion of workers in each occupation multiplied by this weight was used to create a historic lead exposure index; quintiles of this index were used in analyses. AD mortality rates among persons ≥ 65 years old from 1999-2016 were obtained from the Centers for Disease Control and Prevention. The relationship between the historic exposure index and mortality was evaluated using correlation coefficients and linear regression models adjusting for age, sex, education, socioeconomic status (SES). Maps to characterize spatial pattern of historic lead exposure and AD mortality were completed using Geographic Information System (GIS) spatial analysis tools for the U.S. at state level and at county level for Indiana. Results showed that among states, the average AD mortality rate was 202.2 per 100,000 (SD=44.4). Within Indiana, the average AD mortality rate was 209.6 per 100,000 (SD= 64.9). Among Indiana counties, the unadjusted model shows an association of higher HEI with higher AD mortality, with the fifth quintile reaching statistical significance. Results for the adjusted model were not statistically significant. Results for US states for both unadjusted and adjusted regression models show that the third, fourth, and fifth quintiles of the historic exposure index were associated with a significantly lower AD mortality rate when compared to the lowest quintile.</p><p>Conclusion: The first study, using a longitudinal design, shows a positive but non-significant association between BLL and subsequent AD mortality after adjustments for competing risks or design effects. The second study, using a cross-sectional design, showed that newcomers to the US may be a population at higher risk for elevated BPb. The third, ecological study, did not find any significant association between historic lead exposure and AD mortality rates for Indiana counties, however there was a significant association of higher historic lead exposure index with lower AD mortality rates for states in the US.</p>