Neurobiology of the Menopausal Transition

描述（由申请人提供）：绝经过渡期是一个重要的生命过程，显著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，雌激素水平对脑神经回路有显着影响。然而，绝经过渡期的神经生物学机制的研究是缺乏的。该提案结合了丰富的历史数据和访问一个独特的良好特征的妇女人口，过渡更年期，神经心理学测试和国家的最先进的神经影像学技术，以表征更年期过渡的神经生物学。为了验证有关绝经期认知和情感变化机制的假设，我们将从中年妇女中招募，这些妇女自1992年以来一直参与骨健康和代谢研究，包括广泛的激素和周期监测。招募对象为40-55岁的女性，根据促卵泡激素水平和月经出血模式分为绝经前、围绝经期早期、围绝经期晚期和自然绝经后。这项合作将涉及广泛的神经心理学测试，结合经验证的功能性磁共振（fMRI）成像范例，以确定每个小组中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.确定绝经过渡期的特定阶段或特征是否与大脑功能的改变相关，这些改变通过认知和情感任务期间的fMRI-BOLD激活或神经心理学测试来表现。2.描绘卵巢老化与时间老化在大脑功能中的相对贡献，如认知和情感任务期间的fMRI-BOLD激活或神经心理学测试所示。3.证明fMRI-BOLD上记录的认知处理变化是否先于、同时发生或跟随神经心理学测试中可观察到的变化。这些研究将确定激素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规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.