Estrogen Influences on cognitive aging in the monkey

雌激素对猴子认知衰老的影响

• 批准号: 8376633
• 负责人: Mark G Baxter
• 金额: $ 49.7万
• 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/8376633
• 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.

女性认知老化与年龄相关的神经内分泌系统变化密切相关，尤其是 绝经期发生的循环中卵巢类固醇激素的丢失。令人惊讶的发现来自于 女性健康倡议记忆研究表明，激素治疗(HT)在高血压发作后很久才开始 更年期不能改善认知，可能是有害的。这与其他研究形成了鲜明对比。 这表明，在绝经后不久，羟色胺就开始对认知产生有益的影响。为了调和这些 研究结果提出了一种“机会之窗”假说，即FIME有一个有限的时期 绝经后，高压氧可改善认知功能。因为其他相关的健康风险 长期高血压包括心血管疾病和癌症，目前的建议是女性应该短期服用 绝经期开始时的高血压病程，然后解除其限制。我们将在一只特征良好的动物身上进行测试 模型中，羟色胺(对时空工作记忆、视觉再认)的认知效应是否有益 记忆力和分心的脆弱性)在停止超负荷治疗后仍然存在，无论它们是否被填补 在绝经后很长一段时间延迟后开始进行高血压的观察。进行了活体神经成像分析 在行为测试的同时，测试将与认知能力并行地测量神经生物学变化。 这项研究将明确检验“机会之窗”假说，以及认知利益是否可以 在停用高压氧后维持。这些研究将提供关键的翻译洞察力，以了解HT是如何 可以改善衰老的认知结果。 相关性(请参阅说明)： 绝经后妇女的激素替代治疗可以改善包括记忆在内的大脑功能。 我们将在动物模型中测试绝经后激素治疗如何影响其能力 改善大脑功能，无论是在绝经后不久开始治疗才有效， 以及在停止治疗后其有益效果是否持续。这些研究将帮助我们保持 随着年龄的增长，女性的大脑和记忆功能最好。