Neurobiology of the Menopausal Transition

更年期过渡的神经生物学

• 批准号: 7067461
• 负责人: YOLANDA R SMITH
• 金额: $ 31.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067461
• 关键词: aging; bioimaging /biomedical imaging; cerebral cortex; clinical research; cognition; emotions; female; follicle stimulating hormone; functional magnetic resonance imaging; hippocampus; hormone regulation /control mechanism; human middle age (35-64); human subject; menopause; menstrual cycle; neurophysiology; neuropsychological tests; neuropsychology; ovary; postmenopause; steroid hormone; women' s health

DESCRIPTION (provided by applicant): The menopausal transition is an important life process, significantly impacting the cognitive and psychological health of women. Postmenopausal neuroimaging studies of hormone therapy indicate that estrogen levels have significant effects on brain neural circuitry. However, mechanistic studies of the neurobiology of the menopausal transition are lacking. This proposal combines the rich historical data from and access to a uniquely well-characterized population of women, transitioning the menopause, with neuropsychological testing and state-of-the-art neuroimaging techniques, to characterize the neurobiology of the menopausal transition. To test hypotheses concerning mechanisms of menopausal cognitive and affective changes, we will recruit from a well-characterized population of women at the mid-life who have been participants in a bone health and metabolism study involving extensive hormone and cycle monitoring since 1992. Recruits will be women aged 40-55 years, stratified into panels representing premenopause, early perimenopause, late perimenopause and natural postmenopause defined by follicle-stimulating hormone levels and menstrual bleeding patterns. This collaboration will involve extensive neuropsychological testing combined with a validated functional magnetic resonance (fMRI) imaging paradigm to determine brain activation patterns during cognitive and emotional tasks among women of each panel. The Specific Aims include: 1. Identify if specific stages or characteristics of the menopausal transition are associated with alterations in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 2. Delineate the relative contribution of ovarian aging vs. chronological aging in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 3. Demonstrate whether cognitive processing changes noted on fMRI-BOLD precede, occur concurrent, or follow observable changes in neuropsychological testing. These studies will determine the contributions of hormones and aging to changes in cognitive and emotional processing. A better understanding of the areas and sequence of brain processing changes will allow the health community to plan interventions which most effectively preserve cognitive and emotional health for women.

描述（由申请人提供）：更年期过渡是一个重要的生命过程，显着影响女性的认知和心理健康。激素治疗的绝经后神经影像学研究表明，雌激素水平对大脑神经回路有显着影响。然而，缺乏对绝经过渡神经生物学机制的研究。该提案结合了来自更年期过渡的独特女性群体的丰富历史数据和获取的信息，以及神经心理学测试和最先进的神经影像技术，以描述更年期过渡的神经生物学特征。为了检验有关更年期认知和情感变化机制的假设，我们将从一群特征明确的中年女性中招募，这些女性自 1992 年以来一直参与骨骼健康和代谢研究，涉及广泛的激素和周期监测。年龄为 40-55 岁的女性，分为代表绝经前、围绝经早期、围绝经晚期和由卵泡刺激定义的自然绝经后的小组激素水平和月经出血模式。此次合作将涉及广泛的神经心理学测试与经过验证的功能磁共振（fMRI）成像范例相结合，以确定每个小组的女性在认知和情感任务期间的大脑激活模式。具体目标包括： 1. 确定更年期过渡的特定阶段或特征是否与大脑功能的改变相关，如认知和情绪任务期间的 fMRI-BOLD 激活或神经心理学测试所表明的那样。 2. 描述卵巢衰老与时间衰老对大脑功能的相对贡献，这可以通过认知和情感任务期间的 fMRI-BOLD 激活或通过神经心理学测试来证明。 3. 证明 fMRI-BOLD 上记录的认知处理变化是否先于、同时发生或在神经心理学测试中可观察到的变化之后发生。这些研究将确定激素和衰老对认知和情绪处理变化的影响。更好地了解大脑处理变化的区域和顺序将使健康界能够规划最有效地保护女性认知和情感健康的干预措施。