Date of Award
Doctor of Philosophy
Environmental Health Sciences
Amy E Kalkbrenner
Kelly M Bakulski, Keith Dookeran, Ira Driscoll, Linda Wesp, Kurt Svoboda
aging, Alzheimer's Disease, cognitive decline, environmental exposure, environmental justice, heavy metals
The studies described in this dissertation extend our understanding of the relationship of environmental cadmium (Cd) and lead (Pb) exposures with later-life cognitive function and Alzheimer’s Disease (AD), while providing important methodological contributions towards disentangling elements of environmental injustice and sex/gender that may underlie race- and sex-based disparities in later-life cognitive health and development of AD. These studies further contribute to our understanding of prevention efforts for the most at-risk populations in mitigating later-life AD. Roles for environmental exposures in contributing to poor cognitive health and AD in later life are supported by cell and animal research and are an important public health concern in suggesting a means for primary prevention. Epidemiological evidence is strong and consistent linking Pb to later-life cognitive decline, where studies are inconsistent for Cd, perhaps due to failure to account for cigarette smoking and nutritional as sources of Cd, as well as Pb as a co-pollutant. Further, pronounced racial and sex-based disparities in AD prevalence exist: Black Americans (compared with Whites) and females experience double the AD burden. Racial disparities in prevalence suggest clues about AD etiology that may include higher chronic Pb exposures. Differences in life-long exposure to neuroprotective sex steroids point to different abilities to mitigate the neurological damage characteristic of AD that Pb and Cd have both been shown to cause in animal studies. Gaps in these respective areas of literature suggested three lines of investigation for clarifying our understanding of the roles of Cd and Pb on later-life cognition and AD: 1) Does Cd exposure alone drive worse cognition and risk of AD after accounting for confounding effects of cigarette smoking, nutritional sources of Cd, and Pb? 2) Does higher chronic Pb exposure explain some of the racial disparities in later-life cognition among Black vs White Americans? and 3) Does longer lifetime sex steroid exposure mitigate later-life cognitive harms associated with Pb and Cd? The scientific premises for these questions are grounded in animal studies showing both Pb and Cd exposure cause neurological damage characteristic of AD and human studies showing strong links for Pb, but notably inconsistent results for Cd; studies demonstrating Pb exposure due to poverty and deteriorating housing and water infrastructure is more commonly experienced by Black communities given historic and continuing trends of racial segregation and discrimination in housing and socioeconomic opportunities; and in vitro and animal studies showing male and female sex steroids as neuroprotective on the neuro-inflammatory and beta-amyloid deposition processes involved in development of AD. In the studies described in the following manuscripts, I sought to answer the above questions by 1) estimating the association of urinary Cd (reflective of long-term exposure) on a) measures of cognitive score in adults 60 years and older, and b) the risk of AD mortality accounting for the key confounders: cigarette smoking, dietary Cd, and biomarkers of Pb; 2) conducting formal mediation analysis to evaluate proportion of later-life cognitive deficit among people who identify as Black, whereby Black race is considered a marker of racialized experience and exposure to systemic racism, that may be due to higher exposure to environmental Pb; and 3) evaluating a) sex-metal exposure interactions on measures of cognitive scores among male- and female-identified people, and b) among female-identified individuals only, estimating lifetime estrogen exposure-metal interactions on cognitive measures.
Jenson, Tara, "Metal Exposures and Alzheimer’s Disease: Risks in the Context of Environmental Injustice and Sex Steroid Hormones" (2023). Theses and Dissertations. 3280.
Available for download on Thursday, August 28, 2025