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）符合梅奥诊所的研究战略计划，即通过个性化医疗每天为每位患者提供最好的服务。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影响男性和女性一生的两种相关疾病，在表现、对治疗的反应、发病率和死亡率方面存在明显差异。本跨学科SCOR的首要主题是了解与主要激素变化、高血压妊娠障碍、绝经期雌激素缺乏或绝经期激素治疗相关的女性特异性疾病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总体主题。项目1将通过基于人群的方法来检验高血压妊娠史是全因和心血管疾病死亡率、未来心血管疾病和认知障碍的危险因素这一假设。从罗切斯特流行病学项目（REP）中选择的队列将对脑血管反应和认知功能进行前瞻性评估。项目二将研究雌激素治疗对早期绝经期接受雌激素治疗的女性认知健康和认知表现影像学标志物的神经保护作用，并与安慰剂进行比较。早期绝经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（KEEPS）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剂容量，表征血源性微泡和血小板的血栓形成潜力，并定义这些特征与脑微血管扩张剂容量、大脑结构和认知变化之间的关系。行政核心将支持运营和质量控制，临床分析核心将提供标准化的受试者招募和数据

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.