Sex-specific Risk for Vascular Dysfunction and Cognitive Decline

描述(由申请人提供)：在梅奥诊所建立性别差异专门研究中心(SCOR)符合梅奥通过个性化药物为每一位患者提供最佳服务的研究战略计划。性别差异研究是个性化医疗不可或缺的一部分。心血管疾病和认知能力下降是两种相关的疾病，对男性和女性的一生影响不成比例，在表现、治疗反应、发病率和死亡率方面存在明显差异。这一跨学科SCOR的主要主题是了解女性特有的与主要荷尔蒙变化、高血压妊娠障碍、更年期雌激素缺乏或绝经激素治疗相关的情况如何影响女性的脑血管功能和认知。三个独立但相互关联的项目将调查这一总体主题。项目I将使用基于人群的方法来检验这一假设，即高血压妊娠障碍史是全因和心血管死亡、未来心血管疾病和认知障碍的危险因素。从罗切斯特流行病学项目(REP)中选择的队列将被前瞻性地评估脑血管反应和认知功能。项目二将调查雌激素治疗对绝经早期服用雌激素和安慰剂的女性认知健康和认知表现的成像标记物的神经保护作用。更年期早期被认为是雌激素治疗的“机会之窗”。该项目利用了正在进行的Kronos早期雌激素预防研究(Keep)的队列。项目III使用项目I和项目II中定义的队列，将定义脑微血管扩张器能力，表征血液携带的微泡和血小板的血栓形成潜力，并确定这些特征与脑微血管扩张剂能力以及脑结构和认知变化之间的关系。行政核心将支持业务和质量控制，临床分析核心将提供标准化的受试者招募、数据 对所有三个项目进行管理和分析。SCOR对RFA高度响应，因为它解决了通过生命转变影响人的疾病的具体性别差异，它整合了临床和基础研究，并使用了梅奥诊所的独特资源。该项目涉及成像和血液可溶性标记物的新技术方法，以机械地接近疾病过程。此外，确定的基础设施和队列将为未来性别差异研究提供基础。通过“基于性别的视角”观察研究和医疗服务，关注个体的性染色体补充和荷尔蒙状况，是个性化护理的基础。梅奥诊所的性别差异SCOR将促进将健康、疾病和治疗的性别决定因素纳入整个研究和临床企业。此外，SCOR调查员将向特定和一般的国内和国际受众传播性别差异研究。 描述(由申请人提供)：心血管疾病和认知能力下降是两种相关的疾病，对男性和女性一生的影响不成比例。这一跨学科计划将利用创新的工具、成像和诊断技术来了解大脑血液供应的变化如何影响经历过高血压怀孕事件、先兆子痫和更年期的女性的认知。这些研究将确定哪些妇女可能从早期治疗中受益，以在她们的一生过渡期间保持认知健康。

DESCRIPTION (provided by the applicant): Establishing a Specialized Center of Research on Sex Differences (SCOR) at Mayo Clinic is consistent with Mayo's strategic plan for research to best serve every patient, every day, through personalized medicine. Sex differences research is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions disproportionately affecting men and women across their lifespan with distinct differences in manifestations, responses to treatments, morbidity, and mortality. The overarching theme of this interdisciplinary SCOR is to understand how female-specific conditions associated with major hormonal shifts, hypertensive pregnancy disorders, and menopausal estrogen deficiency or menopausal hormone therapy affect cerebrovascular function and cognition in women. Three individual but interrelated projects will investigate the overarching theme. Project I will test the hypothesis that a history of hypertensive pregnancy disorders is a risk factor for all-cause and cardiovascular mortality, future cardiovascular disease, and cognitive impairment by using a population-based approach. Cohorts selected from the Rochester Epidemiology Project (REP) will be evaluated prospectively for cerebrovascular responses and cognitive function. Project II will investigate the neuroprotective effects of estrogen treatment on imaging markers of cognitive health and cognitive performance in women who were treated with estrogens compared with placebo during early menopause. Early menopause is considered the "window of opportunity" for estrogen treatment. This project leverages the cohort of the ongoing Kronos Early Estrogen Prevention Study (KEEPS). Project III, using cohorts defined in Projects I and II, will define cerebral microvascular dilator capacit, characterize the thrombotic potential of blood-borne microvesicles and platelets, and define relationships among those characteristics with cerebral microvascular vasodilator capacity and changes in brain structure and cognition. An administrative core will support operations and quality control, and a clinical analytical core will provide standardized subject recruitment, data management, and analysis for all three projects. The SCOR is highly responsive to the RFA because it addresses specific sex differences underpinning diseases affecting persons through life transitions, it integrates clinical and basic research, and it uses unique resources at Mayo Clinic. This project involves novel technical approaches of imaging and blood-soluble markers to mechanistically approach disease processes. Furthermore, the defined infrastructure and cohorts will provide the basis for future research on sex differences. Viewing research and medical delivery through a "sex-based lens," with attention to an individual's sex chromosomal complement and hormonal status, is fundamental to personalized care. The SCOR on Sex Differences at Mayo Clinic will facilitate incorporation of sex determinants of health, disease, and treatments across the research and clinical enterprise. In addition, the SCOR investigators will disseminate sex-differences research for specific and general national and international audiences. DESCRIPTION (provided by applicant): Cardiovascular disease and cognitive decline are two related conditions disproportionately affecting men and women across their lifespan. This interdisciplinary program will utilize innovative tools imaging and diagnostic techniques to understand how changes in blood supply to the brain affect cognition in women who have experienced a hypertensive pregnancy event, preeclampsia, and menopause. These studies will identify which women might benefit from early treatments to sustain cognitive health across their life transitions.