Date of Award

1-1-2022

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Environmental Health Sciences

Content Description

1 online resource (xvi, 124 pages) : illustrations (some color), map.

Dissertation/Thesis Chair

David O Carpenter

Committee Members

Akiko Hosler, Ramune Reliene, Xiaobo Romeiko, Shao Lin

Keywords

aging, cognitive function, Environmental epidemiology, mixture analysis, Polychlorinated biphenyls, Fish as food, Fishes, Environmental health, Cognition disorders, Mohawk Indians, Nervous system

Subject Categories

Public Health

Abstract

Cognitive decline often occurs with aging, independent of development of neurodegenerative diseases. Little is known about how to prevent cognitive decline or what cofactors, hereditary or environmental, may accelerate or protect against it. In young people, metals, including lead, cadmium, arsenic, methylmercury, and some organic compounds such as polychlorinated biphenyls (PCBs), are known to decrease cognitive function. Consumption of fish is a route of exposure to methylmercury and PCBs, but fish also contain omega-3 fatty acids that are reported to enhance infant neurodevelopment and postnatal cognitive performance. Yet, a recent systematic review concluded that there was inconclusive evidence the omega-3 fatty acids and fish consumption have any positive effects on cognitive function at any stage of life, including during aging. Thus, associations between environmental exposures, fish consumption, and cognitive decline in older adults remain unclear. I have conducted cross-sectional studies to investigate whether environmental toxicants such as metals and PCBs are associated with cognitive decline in older adults or protect against it, using data obtained from the National Health and Nutrition Examination Survey (NHANES), and from the Mohawk Akwesasne community research program. The latter data were previously studied for health outcomes resulting from exposure to PCBs, the DDT metabolite of dichlorodiphenyl-dichloroethylene (DDE), hexachlorobenzene (HCB), and Mirex. In the NHANES 2011 – 2014 cycles, participants aged 60 years and older were given cognitive function modules for immediate and delayed recall memory from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and for executive function with the Digit Symbol Substitution Test (DSST). Blood samples were analyzed for seven metals and urine samples for nineteen metals or metabolites. Fish consumption frequency was self-reported. Distributions between concentrations of each metal or metabolite and cognitive function on each of three tests were determined, and the influence of fish consumption was examined. Performance on all three cognitive tests was reduced by lead and cadmium, but not by methyl mercury. Performance was improved in relation to blood selenium concentrations and by fish consumption. The dramatic association of selenium levels and fish consumption with better cognitive performance was unexpected. In the Mohawk Akwesasne population, a previous study reported decrements in cognitive function from total PCBs exposures. However, it was unclear which PCB congener groups were most important, how PCBs and organochlorine pesticides, DDE, HCB, and Mirex, interact with cognitive function and whether fish consumption may ameliorate cognitive decline. We assessed the exposure roles of primary volatile PCBs, ingested PCBs, and total PCBs, on cognitive decline as measured by DSST scores, and whether fish consumption had a protective effect. For volatile PCBs, comprised of lower chlorinated congeners (chlorine numbers 1 - 4), the major exposure route was inhalation of vapor-phase PCBs. For higher chlorinated congeners (chlorine numbers 6 - 9), dubbed “ingested PCBs”, the major exposure route was via contaminated fish consumption. Total PCBs included the sum of all identified PCB congeners. Results from mixture analysis suggest that the strongest association with reduced cognitive function was due to the more highly chlorinated congeners. Furthermore, there were no beneficial effects of fish consumption, presumably because of the high PCB concentrations in local fish. The NHANES 1999 – 2002 cycles measured a subset of PCB congeners and DSST performance for older adults aged 60 – 85 years. Exposure levels of volatile PCBs, ingested PCBs, total PCBs, DDE, HCB, and Mirex, and associations between each PCB congener group and DSST scores were compared between Mohawk adults and NHANES older adults. This comparison identified whether Mohawk adults showed cognitive decrements from exposure to the subset of PCBs measured in NHANES, identified how exposure levels differed between the highly PCB exposed Mohawk population and NHANES older adults, and demonstrated how the mixture effect of PCBs, DDE, HCB, and Mirex differed between older Mohawk adults and NHANES older adults. Associations between environmental exposures and cognitive function scores were analyzed with linear regression and mixture models. It is important to note that Mohawk adults, who are a heavily PCB exposed population, maintained healthy cognition relative to the U.S. general population of similar age, even though this general population is not heavily exposed to PCBs. Mohawk adults showed mixture effects from exposures to ingested PCBs and total PCBs, HCB, and DDE, which were strongly negatively associated with cognitive function. By comparison, older adults in the NHANES 1999 – 2002 cycle showed adverse mixture effects on cognitive function from DDE, and Mirex exposures, but no significant contribution to the contaminant mixture effect from any PCB congener group. Through my dissertation research, I found associations between metal exposures, PCBs exposures, fish consumption, and cognitive function, and demonstrated mixture effects of those mixture components. In older adults, since the mixture effects of lead, cadmium, methylmercury, selenium, and fish consumption have an overall positive association with executive function, adequate selenium intake and moderate fish consumption may ameliorate lead-, cadmium-, and methylmercury- induced cognitive impairment. Moreover, among Mohawk adults aged 49 – 79 years, I found associations with reduced executive function from exposures to volatile PCBs, ingested PCBs, total PCBs, DDE, and HCB. The general U.S. population is not so highly PCB-exposed, and showed an association between reduced executive function and organochlorine pesticide levels among the older NHANES participants. In this case, fish consumption was not significantly associated with cognitive function. Therefore, Mohawk adults, exposed to PCBs constantly in their daily life, showed an additive negative effect on cognitive function from accumulated PCBs and organochlorine pesticides, while elders from a representative sample of Americans in the NHANES 1999 – 2002 cycle showed significant additive negative effects on cognition only from the organochlorine pesticides.

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