NEUROBIOLOGICAL EFFECTS OF LONG-TERM ESTROGEN REPLACEMENT

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。随着我国女性人口老龄化的不断增加，有关维护和改善绝经后妇女身心健康的问题与我们的社会极为相关。衰老导致大脑功能的退化和老年痴呆症（如阿尔茨海默病（AD））的发病率较高。AD是一种毁灭性的疾病，给国家带来了巨大的经济负担。由于没有治愈或高度有效的治疗方法，预防策略在这种疾病中特别重要。许多研究表明，雌激素的使用可以提高认知能力，并可能预防或延迟衰弱性痴呆的发作。然而，雌激素对认知功能的长期保护作用尚未明确。我们研究的目的是研究女性的衰老过程，并评估绝经后雌激素治疗对健康脑功能的影响。此外，随着长期绝经后激素治疗的健康益处和风险（即乳腺癌）的争论，与AD风险和生活质量相关的信息将有助于为老年妇女的健康护理提供适当的建议。将通过公告板公告、报纸广告和妇女健康登记处（有兴趣参加临床研究的妇女数据库）招募60名妇女。他们将被选择，以便他们是60岁或以上，并已接受激素治疗绝经后没有中断或没有更换。受试者将被招募到三组中，20人从未使用过绝经后激素治疗，20人仅使用雌激素至少10年，20人使用雌激素和孕酮至少10年。将获得所有研究受试者的脑部解剖结构磁共振成像（MRI）和功能性MRI（fMRI）。此外，受试者将接受正电子发射断层扫描（PET），以研究参与认知的胆碱能神经递质系统。将测试激素水平并进行认知测试。将检查所获得的数据，以确定与雌激素加孕酮方案或根本不使用激素相比，雌激素的使用是否会对大脑能力产生最大的积极影响。

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. With the steady increase in our aging female population, issues concerning the maintenance and improvement of the physical and mental health of postmenopausal women are extremely relevant to our society. Aging leads to the deterioration of brain function and a higher incidence of dementias such as Alzheimer's disease (AD). AD is a devastating illness and presents a tremendous economic burden to the country. Since no cures or highly effective therapies exist, preventive strategies are of particular importance in this disease. A number of studies have suggested that estrogen use can enhance cognitive performance and possibly prevent or delay the onset of debilitating dementias. The long-term protective effects of estrogen on cognitive functioning, however, are not clearly established. The goal of our research is to study the aging process in women and evaluate the effects of postmenopausal estrogen therapy on healthy brain function. Furthermore, as the health benefits and risks (i.e. breast cancer) of long-term postmenopausal hormone therapy are debated, information relevant to AD risk and quality of life will assist in appropriate recommendations for the health care of aging women. Sixty women will be recruited through bulletin board announcements, newspaper advertisements and the Women's Health Registry (a database of women interested in participating in clinical research studies). They will be selected so that they are 60 years old or older and have either received hormone therapy without interruption after menopause or no replacement. The subjects will be recruited into three groups, 20 will have never used postmenopausal hormone therapy, 20 will have used estrogen only for at least ten years, and 20 will have used estrogen and progestin for at least ten years. Magnetic Resonance Image (MRI) of anatomy and functional MRI (fMRI) of the brain will be obtained in all study participants. In addition, subjects will undergo a positron emission tomography (PET) scan for the study of a cholinergic neurotransmitter system involved in cognition. Hormone levels will be tested and cognitive tests will be performed. Acquired data will be examined to find out whether estrogen use will have the greatest positive effect on brain capabilities compared to estrogen plus progestin regimen or using no hormones at all.