NEUROBIOLOGICAL EFFECT OF LONG-TERM ESTROGEN REPLACEMENT

描述(由申请者提供)：这项指导以患者为中心的研究 职业发展奖提案包含授课课程、指导课程 说明，以及为应用这些原则而设计的临床研究项目 学到了东西。研究人员的临床研究兴趣在于整合 生殖内分泌学与认知、衰老和脑功能的关系 和神经化学。拟议的临床培训和研究研究 这个应用程序旨在提高她在研究设计方面的技能， 生物统计学、认知神经科学和神经成像技术，与 最终目标是发展成为独立的临床研究人员。这个 K30临床研究培训助学金的课程设置，培养硕士 密歇根大学临床研究设计和统计分析科学系 包括在课程作业中。研究计划的目标是研究 长期激素治疗对健康绝经后妇女的神经生物学影响 女人。60名绝经后妇女，60岁或以上，将被招募参加 这项横断面研究(20人从未使用过激素，20人使用过激素 只使用雌激素至少10年，20人将使用雌激素和 孕酮至少10年)。所有女性都将接受广泛的 神经心理测试电池，计算的单光子发射 胆碱能突触终末标志物的断层扫描(SPECT) 密度、解剖磁共振成像(MRI)和雌二醇量测 还有雌酮。每组10名女性也将接受功能性核磁共振检查 (FMRI)在一项旨在激活受 雌激素，并在阿尔茨海默病中发生改变。不同组之间的比较将 更好地了解激素疗法对大脑的影响 神经化学和认知。

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award proposal contains didactic coursework, mentored instruction, and a clinical research project designed to apply the principles learned. The investigators' clinical research interest is in the integration of reproductive endocrinology with cognition, aging, and brain function and neurochemistry. The proposed clinical training and research studies in this application are designed to increase her skills in study design, biostatistics, cognitive neurosciences and neuroimaging techniques, with the ultimate goal of developing into an independent clinical investigator. The curriculum of the K30 Training Grant in Clinical Research, leading to a Master of Science in Clinical Research Design and Statistical Analysis at the UM, is included in the coursework. The goal of the research proposal is to study the neurobiological effects of long-term hormone therapy in healthy postmenopausal women. Sixty postmenopausal women, 60 years or older, will be recruited for this cross-sectional study (20 will never have used hormones, 20 will have used estrogen only for at least 10 years, and 20 will have used estrogen and progestin for at least 10 years). All women will undergo an extensive neuropsychological testing battery, a single photon emission computed tomography (SPECT) scan with a marker of cholinergic synaptic terminal density, an anatomic magnetic resonance image (MRI), and measures of estradiol and estrone. Ten women from each group will also undergo a functional MRI (fMRI) during a cognitive task designed to activate brain areas affected by estrogen and altered in Alzheimer's Disease. Comparison between groups will offer a greater understanding of the effect of hormone therapies on brain neurochemistry and cognition.