COGNITION AND ESTROGEN IN MIDDLE-AGED FEMALE MONKEYS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。自然绝经或手术绝经导致的卵巢激素丢失对妇女的健康和福祉有广泛的影响。更年期除了增加心血管疾病和骨质疏松症的风险外，还经常导致认知功能的改变，特别是记忆和注意力的改变。希望这些变化会得到改善往往会影响女性对绝经后激素治疗的选择，但缺乏明确的证据。由于安慰剂效应、实验者和受试者的偏见、社会文化因素和伦理考虑，在女性中进行结束性研究是困难的。我们开发了一个猴子更年期模型，它绕过了这些限制，并允许我们检查卵巢激素在灵长类动物大脑中的潜在作用机制。我们正在进行一项纵向研究，以评估手术绝经(卵巢切除)和随后的激素替代治疗对老年雌性恒河猴记忆和注意力的影响。这项研究正在检验卵巢摘除会损害认知功能、激素治疗会恢复或改善认知功能的假设。这些行为研究与脑结构的非侵入性磁共振成像测量同时进行，以确定大脑总体积或特定皮质区域的体积是否会因衰老以及卵巢激素的停用和替代而发生变化，以及大脑结构参数是否与认知表现相关。这些研究提供了卵巢激素对老年女性大脑功能影响的对照测试，以及关于潜在大脑机制的证据。它们将与更年期妇女卵巢激素替代这一困难和有争议的问题直接相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Loss of ovarian hormones due to natural or surgical menopause has wide-ranging consequences for women¿s health and wellbeing. In addition to increasing the risk for cardiovascular disease and osteoporosis, menopause often leads to alterations in cognitive functioning, particularly memory and attention. Hope that these changes will be ameliorated often influences women¿s choices regarding postmenopausal hormone therapy, but clear evidence is lacking. Conclusive studies in women are difficult because of placebo effects, experimenter and subject bias, sociocultural factors, and ethical considerations. We developed a monkey model of menopause that circumvents these limitations and allows us to examine potential mechanisms of ovarian hormone action in the primate brain. We are conducting a longitudinal study to evaluate effects of surgical menopause (ovariectomy) and subsequent hormone replacement treatment on memory and attention in aging female rhesus monkeys. This study is testing the hypotheses that ovariectomy will impair, that and hormone treatment will restore or improve, cognitive function. The behavioral studies are done in parallel with noninvasive magnetic resonance imaging measures of brain structure to determine whether total brain volume, or the volume of specific cortical areas, are altered by aging and by withdrawal and replacement of ovarian hormones, and whether brain structural parameters are correlated with cognitive performance. These studies provide a controlled test of ovarian hormones¿ effects on brain function in aging females, as well as evidence regarding the underlying brain mechanisms. They will have direct relevance to the difficult and controversial issue of ovarian hormone replacement for menopausal women.