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- All Subjects: Cognitive Psychology
- All Subjects: Menopause
Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
Description
Older adults often experience communication difficulties, including poorer comprehension of auditory speech when it contains complex sentence structures or occurs in noisy environments. Previous work has linked cognitive abilities and the engagement of domain-general cognitive resources, such as the cingulo-opercular and frontoparietal brain networks, in response to challenging speech. However, the degree to which these networks can support comprehension remains unclear. Furthermore, how hearing loss may be related to the cognitive resources recruited during challenging speech comprehension is unknown. This dissertation investigated how hearing, cognitive performance, and functional brain networks contribute to challenging auditory speech comprehension in older adults. Experiment 1 characterized how age and hearing loss modulate resting-state functional connectivity between Heschl’s gyrus and several sensory and cognitive brain networks. The results indicate that older adults exhibit decreased functional connectivity between Heschl’s gyrus and sensory and attention networks compared to younger adults. Within older adults, greater hearing loss was associated with increased functional connectivity between right Heschl’s gyrus and the cingulo-opercular and language networks. Experiments 2 and 3 investigated how hearing, working memory, attentional control, and fMRI measures predict comprehension of complex sentence structures and speech in noisy environments. Experiment 2 utilized resting-state functional magnetic resonance imaging (fMRI) and behavioral measures of working memory and attentional control. Experiment 3 used activation-based fMRI to examine the brain regions recruited in response to sentences with both complex structures and in noisy background environments as a function of hearing and cognitive abilities. The results suggest that working memory abilities and the functionality of the frontoparietal and language networks support the comprehension of speech in multi-speaker environments. Conversely, attentional control and the cingulo-opercular network were shown to support comprehension of complex sentence structures. Hearing loss was shown to decrease activation within right Heschl’s gyrus in response to all sentence conditions and increase activation within frontoparietal and cingulo-opercular regions. Hearing loss also was associated with poorer sentence comprehension in energetic, but not informational, masking. Together, these three experiments identify the unique contributions of cognition and brain networks that support challenging auditory speech comprehension in older adults, further probing how hearing loss affects these relationships.
ContributorsFitzhugh, Megan (Author) / (Reddy) Rogalsky, Corianne (Thesis advisor) / Baxter, Leslie C (Thesis advisor) / Azuma, Tamiko (Committee member) / Braden, Blair (Committee member) / Arizona State University (Publisher)
Created2019