Date of Award

Summer 8-15-2016

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The current literature shows discrepant findings as to the degree to which cumulative stress and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis are associated with brain structure and cognitive function in older adults, particularly in brain regions with high expression of receptors for glucocorticoid, and cognitive function reliant upon these regions. Past studies have been heavily focused on total hippocampus while limited studies have examined hippocampal subdivisions or other brain structures. In addition, one key moderator that may influence the associations of cumulative stress and cortisol on brain structure and cognition is the single-nucleotide polymorphisms (SNPs) of the stress-system genes, which has not been investigated in older adults. Therefore, in Aim 1, the current study examined the differential associations of cumulative stress and cortisol with brain structure that have high or low expression of receptors for glucocorticoid, including total hippocampus, hippocampal subdivisions, amygdala, medial prefrontal cortex, and primary visual cortex in cognitively normal older adults. In addition, the current study examined whether the genetic score from SNPs of stress-system genes moderated these associations. Aim 2 examined the differential associations of stress and cortisol on cognitive functions, including memory, fluid intelligence, and crystallized intelligence. The moderating role of the genetic score was examined in Aim 2 as well. In general, no consistent results were found for either aim. Post-hoc analyses showed no consistent moderating role of either age or gender, but suggested timing of stress may be an important factor to consider for future studies. Overall, the current study suggests that stress and cortisol may not have robust associations with brain structure and cognition in older adults. However, future longitudinal studies with systemic incorporation of various factors, such as timing of stress and multiple cortisol measures across the day, may reveal more consistent associations of stress and cortisol.

Language

English (en)

Chair and Committee

Denise Head

Committee Members

David Balota, Tony Buchanan, John Cirrito, Tamara Hershey

Comments

Permanent URL: https://doi.org/doi:10.7936/K7P26WHW

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