Estrogen Use in Protection from Cognitive Decline

描述(申请人提供)：这是一项新的R01拨款申请：“雌激素用于预防认知功能减退”，旨在评估雌激素替代疗法对有认知功能减退风险的绝经后女性的效果。我们已经收集了试点数据，这些数据表明，在阿尔茨海默病高危人群中使用雌激素可能会保护局部大脑代谢，这是通过18-氟代脱氧葡萄糖(FDG-PET)的正电子发射断层扫描(FDG-PET)测量的。共有71名年龄在50-65岁的绝经后女性服用雌激素，她们将被随机分为继续使用或停止使用，并将接受长达两年的跟踪调查，以了解大脑新陈代谢和认知表现的变化。受试者将接受FDG-PET扫描和神经心理学评估，最初和在两年的随访期结束时。这些程序将使我们能够评估绝经后妇女在基线和随机继续与停止雌激素替代治疗时的局部，特别是顶叶、颞叶和后扣带区的大脑葡萄糖代谢以及认知能力。假设停止使用雌激素的受试者比继续使用雌激素的受试者表现出更多的下降证据。该项目将通过以下方式扩大对雌激素影响的现有知识：(1)确定有认知能力下降风险的绝经后女性使用雌激素是否对大脑新陈代谢具有保护作用；(2)确定认知能力下降的早期预测因素；以及(3)制定绝经后女性使用雌激素的指南。

DESCRIPTION (provided by applicant): This is a new application for an R01 grant: "Estrogen use in protection from cognitive decline" designed to assess effects of estrogen replacement therapy among postmenopausal women at risk for cognitive decline. We have collected pilot data, which suggest that estrogen use among older persons at risk for Alzheimer's Disease may be protective of regional cerebral metabolism, as measured by position emission tomography with 18-fluorodeoxyglucose (FDG-PET). A total of 71 postmenopausal women ages 50-65, estrogen users, will be randomized to continue or discontinue use and will be followed up to two years for changes in cerebral metabolism and cognitive performance. Subjects will undergo FDG-PET scans and neuropsychological assessments, initially and at the end of the two-year follow-up period. These procedures will allow us to evaluate regional, especially parietal, temporal, and posterior cingulate, cerebral glucose metabolism along with cognitive performance in postmenopausal women at baseline and upon random continuation vs. discontinuation of estrogen replacement therapy. Subjects who to discontinue estrogen use are hypothesized to show more evidence of decline than those who continue do. This project will expand current knowledge of effects of estrogen, by : (1) determining whether estrogen use among postmenopausal women at risk for cognitive decline is protective of brain metabolism; (2) identifying early predictors for cognitive decline; and (3) developing guidelines for estrogen use in postmenopausal women.