Human Physiology Theses and Dissertations

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Browsing Human Physiology Theses and Dissertations by Subject "aging"

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    Effects of Fatigue on Balance Control During Dual-task Walking
    (University of Oregon, 2020-02-27) Chen, Szu-Hua; Chou, Li-Shan
    Fatigue is one of the most frequently mentioned symptoms among older adults. Although there were many studies examining effects of fatigue on walking and balance control, the findings were inconclusive due to methodology discrepancy. In addition, the cognitive component is often neglected. Therefore, four studies were conducted in this dissertation to investigate how fatigue affects balance control during dual-task locomotion in older adults using a laboratory fatiguing protocol, and further, how these findings could be applied in real-life settings. In the first study, we demonstrated the use of a repetitive sit-to-stand protocol by examining changes in inter-joint coordination variability along the course of the protocol. The findings suggested that the knee-ankle coordination variability was higher towards the end of protocol. In the second and the third experiments, such fatiguing protocol was applied. Results from the second study suggested that participants regardless of age walked faster after fatigue when concurrently responding to a working memory test. Moreover, young adults showed a greater and faster mediolateral center of mass sway after fatigue; whereas older adults demonstrated a shorter reaction time from pre- to post-fatigue while maintaining a similar body sway during walking. The results from the third study followed the same trend, in which significantly deteriorated balance control during obstacle-crossing was only found in young adults but not in older adults. Taken together, healthy older adults might have a better adaptation to a fatigued status induced by a repetitive sit-to-stand protocol. In the last study, the connection between findings from laboratory experiments and real-life scenarios was explored through examining the effect of fatigue in three older workers following a day-long of occupational activities. Our results showed that some changes observed after work were in line with that observed in the laboratory, but some were opposite or demonstrated unique fatigue adaptations, such as increased body sway, which was not identified when the results were pooled together. Although conclusive interpretation could not be made given the descriptive nature of the study, it highlights the necessity of subgroup analysis and targets the future recruitment on fatigue-prone population. This dissertation includes unpublished co-authored material.
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    Title: The Triple Threat: Estrogen Deficiency, APOE Genotype, and Age on Cerebral Vascular Function
    (University of Oregon, 2025-02-24) Kehmeier, Mackenzie; Walker, Ashley
    As late-onset of Alzheimer’s disease (LOAD) prevalence increases, efforts toward elucidating mechanisms underlying LOAD pathology are needed. Three of the greatest genetic risk factors for late-onset Alzheimer’s disease are age, female sex, and the apolipoprotein E ε4 (E4) genotype. Two-thirds of LOAD cases are females, and perimenopause coincides with the prodromal phase of LOAD. Post-menopausal females with an E4 allele have higher rates of LOAD compared with age-matched males with an E4 allele, suggesting an interaction between APOE genotype, age, and estrogen deficiency. Cerebral endothelial function can alter cerebral blood flow (CBF) and compromise the blood-brain barrier. Cerebral endothelial dysfunction is a common link between the E4 genotype, estrogen deficiency, and LOAD. However, the interaction effect of APOE, age, and estrogen on cerebral endothelial cell function and mitochondrial health is unknown. I hypothesized that estrogen fluctuation and deficiency modulate cerebrovascular function, and this function is further impaired in the presence of the E4 genotype and age. The following aims were completed to test my hypotheses. Aim 1: Determine the role of phytoestrogens and female sex hormones on cerebral vascular function. Aim 1 encompasses Chapters 2 & 3 of this dissertation and the main findings were two-fold. 1) The estrous cycle in female mice influenced large artery stiffness but not ex vivo endothelial function in resistance arteries. Thus, accounting for the estrous cycle for ex vivo endothelial function is not needed but should be accounted for when measuring in vivo large artery stiffness. 2) Phytoestrogens, specifically soy in the rodent diet, influenced cerebral vascular function, insulin signaling, and cognitive function. This study also confirmed previous findings that ovariectomy impairs endothelial function and, for the first time, demonstrated that a soy diet prevents adverse effects of ovariectomy on insulin-mediated vasodilation. Aim 2: Determine the interaction effect of APOE genotype and estrogen deficiency on cerebral vascular function, in vivo whole-body metabolism, and ex vivo cerebral vascular mitochondrial health. The findings from Aim 2 are shown in Chapter 4. In E3 and E4 female mice, I investigated how estrogen deficiency influenced endothelial and mitochondrial function. Overall, these results indicated that APOE genotype modulates the impact of estrogen on the cerebrovasculature. 17β-estradiol enhanced cerebrovascular function and mitochondrial function in E3 mice, while E4 mice conferred resistance to estrogen status. Aim 3: Determine the interaction effect of aging and APOE genotype on cerebral vascular and cognitive function. Aim 3 is addressed in Chapter 5, and investigated the influence of age and APOE genotype on vascular function and cognition. The major results of this study demonstrated that age has a greater influence on cerebral vascular function than the E4 genotype. These series of studies highlight the importance of considering sex and age as a biological variable that can influence one’s results. The major novel finding of these studies is that the E4 allele confers resistance to estrogen status, and the broader impact of this finding is that consideration of APOE genotype is needed when prescribing hormone replacement therapy for menopausal females. This dissertation includes previously published and co-authored material.