PERIMENOPAUSAL SYMPTOMS AND BIOMARKERS AND COGNITIVE FUNCTION IN POSTMENOPAUSAL

在4500多万绝经后的美国妇女中，有相当数量的人会患上痴呆症或 认知障碍。我们的围绝经期脑老化和阿尔茨海默病项目寻求 发现在围绝经期过渡期间大脑中发生的生物变化 导致预测阿尔茨海默病(AD)病理发展风险的表型并确定 这些变化发生的机制，并将这些发现转化为确定最佳 防止转变为围绝经期高危表型的时机和策略。项目4将 描述围绝经期和绝经期的生物学特征，并评估 绝经早期和绝经晚期妇女的这些特征与认知之间的关系。项目4将(1) 确定生物标志物在围绝经期和AD中是否重要 描述绝经后女性在绝经早期和绝经后期的特征；(2)确定是否和 这些生物标志物在多大程度上与认知有关；以及(3)评估服用 更年期激素治疗将改变这些标志物。项目4将使用数据和存储的组织样本 来自NIA资助的Eariy与晚期雌激素干预试验(ELITE)(R01AG-024154)试验 四个假设：(1)围绝经期转变导致生物能量和炎症表型 与阿尔茨海默病风险的生物标志物一致；(2)围绝经期过渡将导致多发性 表型，其亚群将预测阿尔茨海默病的生物标记物的风险； 围绝经期过渡是决定卵巢激素反应及其作用的关键窗口。 预防与增加AD早期生物标志物的风险；以及(4)卵巢激素和 生物能量干预可以改变阿尔茨海默病生物标记物的发展 围绝经期高危表型。该项目将与分析核心和管理核心密切合作 关于样本和数据的处理，以及关于生物能量、炎症和饮食分析的项目1-3。 相关性(请参阅说明)： 超过60%的阿尔茨海默病(AD)患者是女性。围绝经期计划的这一阶段 该项目旨在评估、识别和预防与围绝经期相关的大脑变化，预测更年期增加 广告风险。项目4将确定更年期更年期的潮红时间和持续时间是否 与认知能力下降的风险增加有关。项目4将评估荷尔蒙和饮食的影响 对认知功能的干预，并确定降低认知功能下降风险的治疗窗口。

A substantial number of the more than 45 million postmenopausal US women will develop dementia or cognitive impairment. Our Perimenopause in Brain Aging and Alzheimer's Disease Program Project seeks to discover the biological transformations occurring in the brain during the perimenopausal transition which can result in phenotypes predictive of risk for development of Alzheimer's disease (AD) pathology and to identify the mechanisms by which these changes occur, and translate these discoveries to determine the optimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. Project 4 will characterize biological profiles from the perimenopausal and postmenopausal periods, and evaluate the association of these profiles with cognition in women who are in eariy vs. late menopause. Project 4 will (1) determine whether biomarkers hypothesized to be important in the perimenopausal period and in AD characterize the postmenopausal human female in eariy vs. later menopause; (2) determine whether and to what extent these biomarkers are associated with cognition; and (3) evaluate whether administration of menopausal hormone therapy will modify these markers. Project 4 will use data and stored tissue samples from the NIA-funded Eariy versus Late Intervention Trial with Estrogen (ELITE) (R01AG-024154) trial to test four hypotheses: (1) The perimenopause transition results in the bioenergetic and inflammatory phenotype consistent with biomarkers of Alzheimer's disease risk; (2) the perimenopause transition will result in multiple phenotypes, subgroups of which will predict risk of developing biomarkers of Alzheimer's disease; (3) the perimenopause transition is a critical window that determines ovarian hormone response and their role in prevention vs. increased risk of developing eariy biomarkers of AD; and (4) ovarian hormone and bioenergetic interventions can modify development of biomarkers of Alzheimer's disease in the perimenopausal at-risk phenotype. This Project will work closely with Analytic Core and Administrative Core on processing samples and data, and with Projects 1-3 on bioenergetic, inflammatory, and dietary analyses. RELEVANCE (See instructions): More than 60% of Alzheimer's disease (AD) patients are women. This phase of our Perimenopause Program Project seeks to evaluate, identify and prevent perimenopause-related brain changes predictive of increased AD risk. Project 4 will determine whether flushing and the timing and duration of perimenopause are associated with increased risk of cognitive decline. Project 4 will evaluate the impact of hormonal and dietary interventions on cognitive function, and identify a treatment window to reduce risk of cognitive decline.