PERIMENOPAUSAL SYMPTOMS AND BIOMARKERS AND COGNITIVE FUNCTION IN POSTMENOPAUSAL

围绝经期症状和生物标志物以及绝经后的认知功能

• 批准号: 8379631
• 负责人: ROBERTA EILEEN BRINTON
• 金额: $ 15.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8379631
• 关键词: Alzheimer' s Disease; Alzheimer' s disease risk; Animals; Bioenergetics; Biological; Biological Markers; Brain; Brain region; Cognition; Cognitive; Data; Dementia; Development; Diet; Dietary Intervention; Estrogens; Fatty acid glycerol esters; Flushing; Funding; Hormonal; Hot flushes; Impaired cognition; Inflammatory; Instruction; Intervention; Intervention Trial; Lead; Link; Menopause; Metabolic; Mission; Operative Surgical Procedures; Ovarian hormone; Pathology; Patients; Performance; Perimenopause; Phase; Phenotype; Placebos; Play; Postmenopause; Prevention; Principal Investigator; Process; Risk; Role; Sampling; Severities; Subgroup; Symptoms; Testing; Time; Tissue Sample; Translating; Vasomotor; Woman; Work; aging brain; cognitive function; hormone therapy; human female; prevent; programs; response

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.

超过4500万绝经后的美国妇女中有相当多的人将患上痴呆症或 认知障碍我们的围绝经期脑老化和阿尔茨海默病计划项目旨在 发现在围绝经期过渡期间大脑中发生的生物学转变， 导致预测阿尔茨海默病（AD）病理发展风险的表型，并鉴定 这些变化发生的机制，并将这些发现转化为确定最佳的 预防转化为围绝经期高危表型的时机和策略。项目4将 表征围绝经期和绝经后时期的生物学特征，并评估 这些特征与处于更年期早期与晚期的妇女的认知之间的关联。项目4将（1） 确定是否假设生物标志物在围绝经期和AD中重要 表征绝经早期与绝经后期的绝经后人类女性;（2）确定是否 这些生物标志物与认知相关的程度;和（3）评估施用 绝经期激素治疗将改变这些标志物。项目4将使用数据和储存的组织样本 从NIA资助的雌激素早期与晚期干预试验（ELITE）（R 01 AG-024154）试验中， 四个假说：（1）围绝经期过渡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个 表型，其亚组将预测发展阿尔茨海默病生物标志物的风险;（3） 围绝经期过渡期是决定卵巢激素反应及其在 预防相对于发展AD的早期生物标志物的风险增加;和（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志物的发展， 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 处理样品和数据，并与项目1-3生物能量，炎症和饮食分析。 相关性（参见说明）： 超过60%的阿尔茨海默病（AD）患者是女性。我们的围绝经期计划的这个阶段 该项目旨在评估、识别和预防围绝经期相关的大脑变化， AD风险。项目4将确定是否冲洗和围绝经期的时间和持续时间， 与认知能力下降的风险增加有关。项目4将评估激素和饮食对 认知功能的干预，并确定一个治疗窗口，以降低认知能力下降的风险。