Neurobiology of the Menopausal Transition

描述(申请人提供)：更年期过渡是一个重要的生命过程，对女性的认知和心理健康有重大影响。激素治疗的绝经后神经成像研究表明，雌激素水平对大脑神经回路有显著影响。然而，缺乏对更年期转变的神经生物学的机械性研究。这一建议结合了来自独特的、特征良好的更年期妇女群体的丰富历史数据，以及神经心理测试和最先进的神经成像技术，以表征更年期过渡的神经生物学。为了测试有关更年期认知和情感变化机制的假设，我们将从一组具有良好特征的中年女性人群中招募自1992年以来一直参与一项涉及广泛激素和周期监测的骨骼健康和新陈代谢研究。新兵将是年龄在40岁至55岁之间的女性，分成代表绝经前、围绝经期早期、围绝经期晚期和自然绝经后的小组，以卵泡刺激素水平和月经出血模式来定义。这项合作将涉及广泛的神经心理测试，并结合经过验证的功能磁共振(FMRI)成像范例，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变化有关，如认知和情感任务中的fMRI大胆激活或神经心理测试所表明的那样。2.描述卵巢老化和时间老化对大脑功能的相对贡献，这可以通过认知和情绪任务中的fMRI-BOLD激活或神经心理测试来体现。3.证明fMRI上注意到的认知加工变化--粗体是在神经心理测试中可观察到的变化之前、同时发生还是之后发生。这些研究将确定荷尔蒙和衰老对认知和情绪处理变化的贡献。更好地了解大脑处理变化的区域和顺序将使卫生界能够计划最有效地保护女性认知和情绪健康的干预措施。

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.