Estrogen Use in Protection from Cognitive Decline

描述（由申请人提供）：这是一项R01拨款的新申请：“雌激素用于预防认知能力下降”，旨在评估雌激素替代疗法对有认知能力下降风险的绝经后妇女的影响。我们收集了试点数据，这些数据表明，在有阿尔茨海默病风险的老年人中使用雌激素可能对局部脑代谢有保护作用，这是用18-氟脱氧葡萄糖（FDG-PET）的位置发射断层扫描测量的。共有71名年龄在50-65岁的绝经后女性，雌激素使用者，将被随机分配继续或停止使用，并将随访两年，以观察脑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，在最初和两年随访期结束时进行。这些程序将允许我们评估区域，特别是顶叶，颞叶和后扣带，脑葡萄糖代谢以及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认知表现。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衰退迹象。该项目将通过：(1)确定有认知能力下降风险的绝经后妇女使用雌激素是否对脑代谢有保护作用，从而扩大目前对雌激素作用的认识；(2)识别认知能力下降的早期预测因子；(3)制定绝经后妇女雌激素使用指南。

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.