Neurobiology of the Menopausal Transition

描述（申请人提供）：绝经过渡期是一个重要的生命过程，对女性的认知和心理健康有重要影响。绝经后激素治疗的神经影像学研究表明，雌激素水平对脑神经回路有显著影响。然而，缺乏对绝经期神经生物学机制的研究。本研究结合了丰富的历史数据和对绝经期过渡妇女的独特特征，结合神经心理学测试和最先进的神经成像技术，来描述绝经期过渡的神经生物学特征。为了验证有关绝经期认知和情感变化机制的假设，我们将从一组特征明确的中年妇女中招募，这些妇女自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代谢研究。招募对象将是年龄在40-55岁之间的女性，按促卵泡激素水平和月经出血模式分为绝经前、早期围绝经期、晚期围绝经期和自然绝经后的小组。此次合作将包括广泛的神经心理学测试，并结合功能性磁共振成像（fMRI）成像范式，以确定每个小组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。通过认知和情绪任务中fMRI-BOLD激活或神经心理学测试，确定更年期过渡的特定阶段或特征是否与脑功能改变有关。2. 通过认知和情绪任务时fMRI-BOLD激活或神经心理测试，描述卵巢衰老与时间衰老对脑功能的相对贡献。3. 证明fMRI-BOLD记录的认知加工变化是先于神经心理测试的可观察变化，还是同时发生的，还是随后发生的。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卫生界能够计划最有效地保护妇女认知和情感健康的干预措施。

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.