Estrogen Influences on cognitive aging in the monkey

雌激素对猴子认知衰老的影响

• 批准号: 8433388
• 负责人: Mark G Baxter
• 金额: $ 53.24万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8433388
• 关键词: Acute; Affect; Aftercare; Age; Age-associated memory impairment; Aging; Animal Model; Animals; Behavior assessment; Behavioral; Brain; Cardiovascular Diseases; Clinical Data; Cognition; Cognitive; Cognitive aging; Data; Estrogens; Event; Goals; Health; Hormone replacement therapy; Hormones; Injection of therapeutic agent; Instruction; Intervention; Long-Term Effects; Macaca mulatta; Malignant Neoplasms; Measures; Mediating; Memory; Menopause; Molecular; Monkeys; Neurobiology; Neurocognitive; Neurosecretory Systems; Operative Surgical Procedures; Outcome; Ovarian; Ovarian Steroid Hormone; Ovarian hormone; Ovariectomy; Postmenopause; Principal Investigator; Publications; Regimen; Reporting; Resources; Risk; Short-Term Memory; Stroke; Symptoms; Testing; Time; Treatment Protocols; Visual; Withdrawal; Woman; Women' s Health; Work; age group; age related; aged; aging brain; behavior test; cardiovascular disorder risk; comparison group; distraction; hormone therapy; improved; in vivo; insight; memory recognition; neuroimaging; nonhuman primate; object recognition; programs; research study; response; spatiotemporal

Cognitive aging in women is closely related to age-related changes in neuroendocrine systems, particulariy the loss of circulating ovarian steroid hormones that occurs in menopause. Surprising findings from the Women's Health Initiative Memory Study showed that hormone treatment (HT) begun long after the onset of menopause failed to improve cognition and may have been harmful. This contrasts with other studies indicating beneficial cognitive effects of HT begun soon after the onset of menopause. To reconcile these findings a 'window of opportunity' hypothesis has been proposed, such that there is a limited period of fime after menopause during which HT may improve cognifion. Because of other health risks associated with long-term HT including cardiovascular disease and cancer, current advice is for women to take a short course of HT at the onset of menopause and then disconfinue it. We will test, in a well-characterized animal model, whether beneficial cognitive effects of HT (on spatiotemporal working memory, visual recognition memory, and vulnerability to distraction) persist after discontinuation of HT, and whether they are sfill observed when HT is begun after a long delay post-menopause. In vivo neuroimaging analyses conducted concurrently with behavioral tesfing will measure neurobiological changes in parallel with cognitive ability. This study will test the 'window of opportunity' hypothesis explicitly, as well as whether cognitiye benefits can be maintained after withdrawal of HT. These studies will provide critical translational insights into how HT can improve cognitive outcomes of aging. RELEVANCE (See instructions): Hormone replacement therapy in women after menopause can improve brain funcfion, including memory. We will test, in an animal model, how the fiming of hormone therapy after menopause affects its ability to improve brain function, both in terms of whether therapy must begin soon after menopause to be effective, and whether its beneficial effects persist after therapy is discontinued. These studies will help us maintain best brain and memory function in women as they age.

女性的认知老化与神经内分泌系统的年龄相关变化密切相关， 绝经期卵巢类固醇激素循环的丧失。令人惊讶的发现， 妇女健康倡议记忆研究表明，激素治疗（HT）开始后很久， 更年期不能改善认知能力，可能是有害的。这与其他研究形成对比 这表明在绝经期开始后不久HT就开始产生有益的认知效果。调和这些 研究结果提出了“机会之窗”假说，即存在有限的时间段， 在绝经后，HT可改善认知功能。由于其他健康风险与 长期HT包括心血管疾病和癌症，目前的建议是妇女采取短期 我们将在一个特征良好的动物身上进行测试， 模型，HT是否有益的认知效应（对时空工作记忆，视觉识别 记忆力和易分心）在HT停止后持续存在，以及它们是否会在HT停止后消失。 绝经后长时间延迟后开始HT时观察到。进行的体内神经成像分析 与行为测试同时进行的将测量与认知能力平行的神经生物学变化。 这项研究将明确测试“机会之窗”假设，以及认知益处是否可以 在HT退出后保持。这些研究将提供关键的翻译见解如何HT 可以改善衰老的认知结果。 相关性（参见说明）： 绝经后妇女的激素替代疗法可以改善大脑功能，包括记忆力。 我们将在一个动物模型中测试绝经后激素治疗的效果如何影响它的能力， 改善大脑功能，无论是在治疗是否必须在绝经后开始才有效方面， 以及在治疗停止后其有益效果是否持续。这些研究将帮助我们保持 大脑和记忆功能最好的女性。