Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Public Health

First Advisor's Name

Deodutta Roy

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Changwon Yoo

Second Advisor's Committee Title

Co-Committee Chair

Third Advisor's Name

Alok Deoraj

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Vijaya Narayanan

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Quentin Felty

Fifth Advisor's Committee Title

Committee Member

Keywords

Estrogenic Chemicals, Endocrine Disrupting Chemicals, Brain Health, Phthalates, BPA, PCB, Arsenic, Cadmium, Manganese, Neurodegenerative Disease, Neurodegeneration, NHANES, Alzheimer's Disease, Memory, Nuclear Respiratory Factor 1, Gene Networks

Date of Defense

5-11-2018

Abstract

The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that are both estrogen and EEDC-sensitive, we found several genes involved in the gene pathways of Alzheimer’s disease (AD): APBB2, EIF2S1, ENO1, MAPT, and PAXIP1. Using the Center for Disease Control and Prevention (CDC), National Health and Nutrition Examination Survey (NHANES) 2011-2014 datasets to assess EEDC bioburden and associations with surrogate indicators of brain health, which include cognitive scores, memory questions, and taste and smell data, we found phthalate bioburden to be significantly higher in those with adverse brain health vii and significantly higher in females. In our logistic regression model when controlling for all known and suspected covariates in AD, in females, the phthalates in females ECP, MBP, MOH, MZP, and MIB in males and the phthalates COP, ECP, MBP, MC1, MEP, MHH, MOH, and MIB were significantly associated with poor cognitive test scores, poor memory, and taste and smell dysfunction. Among the metalloestrogens, Cd bioburden was higher in those with poor cognitive performance, poor memory, and taste and smell dysfunction, with the trend more significant in males. Among oral contraceptive (OC) and HRT (hormone replacement therapy) use, in our logistic regression model when controlling for all known and suspected covariates in AD, past OC and HRT use was associated with better cognitive test scores. The study provides further evidence of the complex role EEDCs play in overall brain health through other biological mechanisms and fills a gap in knowledge that demonstrates EEDCs effects on brain health in a geriatric age population.

Identifier

FIDC006573

Available for download on Sunday, July 19, 2020

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