Matching Items (3)
Description
Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive decline, and other symptoms that reduce quality of life. To ameliorate these negative consequences, estrogen-containing hormone therapy is prescribed. Findings from clinical and pre-clinical research studies suggest that menopausal hormone therapies can benefit memory and associated neural substrates. However, findings are variable, with some studies reporting null or even detrimental cognitive and neurobiological effects of these therapies. Thus, at present, treatment options for optimal cognitive and brain health outcomes in menopausal women are limited. As such, elucidating factors that influence the cognitive and neurobiological effects of menopausal hormone therapy represents an important need relevant to every aging woman. To this end, work in this dissertation has supported the hypothesis that multiple factors, including post-treatment circulating estrogen levels, experimental handling, type of estrogen treatment, and estrogen receptor activity, can impact the realization of cognitive benefits with Premarin hormone therapy. We found that the dose-dependent working memory benefits of subcutaneous Premarin administration were potentially regulated by the ratios of circulating estrogens present following treatment (Chapter 2). When we administered Premarin orally, it impaired memory (Chapter 3). Follow-up studies revealed that this impairment was likely due to the handling associated with treatment administration and the task difficulty of the memory measurement used (Chapters 3 and 4). Further, we demonstrated that the unique cognitive impacts of estrogens that become increased in circulation following Premarin treatments, such as estrone (Chapter 5), and their interactions with the estrogen receptors (Chapter 6), may influence the realization of hormone therapy-induced cognitive benefits. Future directions include assessing the mnemonic effects of: 1) individual biologically relevant estrogens and 2) clinically-used bioidentical hormone therapy combinations of estrogens. Taken together, information gathered from these studies can inform the development of novel hormone therapies in which these parameters are optimized.
ContributorsEngler-Chiurazzi, Elizabeth (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Hoffman, Steven (Committee member) / Arizona State University (Publisher)
Created2013
Description
Identifying modifiable causes of chronic disease is essential to prepare for the needs of an aging population. Cognitive decline is a precursor to the development of Alzheimer's and other dementing diseases, representing some of the most prevalent and least understood sources of morbidity and mortality associated with aging. To contribute to the literature on cognitive aging, this work focuses on the role of vascular and physical health in the development of cognitive trajectories while accounting for the socioeconomic context where health disparities are developed. The Assets and Health Dynamics among the Oldest-Old study provided a nationally-representative sample of non-institutionalized adults age 65 and over in 1998, with biennial follow-up continuing until 2008. Latent growth models with adjustment for non-random missing data were used to assess vascular, physical, and social predictors of cognitive change. A core aim of this project was examining socioeconomic and racial/ethnic variation in vascular predictors of cognitive trajectories. Results indicated that diabetes and heart problems were directly related to an increased rate of memory decline in whites, where these risk factors were only associated with baseline word-recall for blacks when conditioned on gender and household assets. These results support the vascular hypotheses of cognitive aging and attest to the significance of socioeconomic and racial/ethnic variation in vascular influences on cognitive health. The second substantive portion of this dissertation used parallel process latent growth models to examine the co-development of cognitive and functional health. Initial word-recall scores were consistently associated with later functional limitations, but baseline functional limitations were not consistently associated with later word-recall scores. Gender and household income moderated this relationship, and indicators of lifecourse SES were better equipped to explain variation in initial cognitive and functional status than change in these measures over time. Overall, this work suggests that research examining associations between cognitive decline, chronic disease, and disability must account for the social context where individuals and their health develop. Also, these findings advocate that reducing socioeconomic and racial/ethnic disparities in cognitive health among the aging requires interventions early in the lifecourse, as disparities in cognitive trajectories were solidified prior to late old age.
ContributorsBishop, Nicholas Joseph (Author) / Kronenfeld, Jennie J. (Thesis advisor) / Haas, Steven A. (Committee member) / Eggum, Natalie D. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Cognitive function is multidimensional and complex, and research indicates that it is impacted by age, lifetime experience, and ovarian hormone milieu. One particular domain of cognitive function that is susceptible to age-related decrements is spatial memory. Cognitive practice can affect spatial memory when aged in both males and females, and in females alone ovarian hormones have been found to alter spatial memory via modulating brain microstructure and function in many of the same brain areas affected by aging. The research in this dissertation has implications that promote an understanding of the effects of cognitive practice on aging memory, why males and females respond differently to cognitive practice, and the parameters and mechanisms underlying estrogen's effects on memory. This body of work suggests that cognitive practice can enhance memory when aged and that estrogen is a probable candidate facilitating the observed differences in the effects of cognitive practice depending on sex. This enhancement in cognitive practice effects via estrogen is supported by data demonstrating that estrogen enhances spatial memory and hippocampal synaptic plasticity. The estrogen-facilitated memory enhancements and alterations in hippocampal synaptic plasticity are at least partially facilitated via enhancements in cholinergic signaling from the basal forebrain. Finally, age, dose, and type of estrogen utilized are important factors to consider when evaluating estrogen's effects on memory and its underlying mechanisms, since age alters the responsiveness to estrogen treatment and the dose of estrogen needed, and small alterations in the molecular structure of estrogen can have a profound impact on estrogen's efficacy on memory. Collectively, this dissertation elucidates many parameters that dictate the outcome, and even the direction, of the effects that cognitive practice and estrogens have on cognition during aging. Indeed, many parameters including the ones described here are important considerations when designing future putative behavioral interventions, behavioral therapies, and hormone therapies. Ideally, the parameters described here will be used to help design the next generation of interventions, therapies, and nootropic agents that will allow individuals to maintain their cognitive capacity when aged, above and beyond what is currently possible, thus enacting lasting improvement in women's health and public health in general.
ContributorsTalboom, Joshua S (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Conrad, Cheryl D. (Committee member) / Neisewander, Janet L (Committee member) / West, Stephen G. (Committee member) / Arizona State University (Publisher)
Created2011