Sex-specific Risk for Vascular Dysfunction and Cognitive Decline

血管功能障碍和认知能力下降的特定性别风险

• 批准号: 8532797
• 负责人: VIRGINIA M MILLER
• 金额: $ 106.75万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8532797
• 关键词: Address; Affect; Attention; Basic Science; Blood; Blood Platelets; Blood Vessels; Brain; Cardiovascular Diseases; Cardiovascular system; Caring; Cerebrum; Characteristics; Clinic; Clinical; Clinical Research; Cognition; Cognitive; Complement; Diagnostic Procedure; Dilator; Disease; Early treatment; Epidemiology; Estrogens; Event; Female; Functional disorder; Future; Health; Hormonal; Image; Imaging Techniques; Impaired cognition; Individual; International; Life; Longevity; Medical Research; Medicine; Menopause; Morbidity - disease rate; Patients; Performance; Persons; Placebos; Pre-Eclampsia; Pregnancy; Prevention; Process; Quality Control; Recording of previous events; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Sex Characteristics; Specialized Center; Strategic Planning; Structure; Testing; Vascular blood supply; Vasodilator Agents; Woman; base; cerebrovascular; cognitive function; cohort; data management; experience; hormone therapy; innovation; lens; men; mortality; novel; operation; population based; pregnancy disorder; programs; response; sex; tool

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.

描述（由申请人提供）：在Mayo Clinic建立专业的性别差异研究中心（SCOR）与Mayo的战略研究计划一致，以每天通过个性化医学为每天为每位患者提供服务。性别差异研究是个性化医学不可或缺的。心血管疾病和认知能力下降是两个相关条件不成比例地影响其在其寿命中的男性和女性，在表现，对治疗的反应，发病率和死亡率方面存在明显差异。这种跨学科的SCOR的总体主题是了解女性特异性疾病与主要荷尔蒙转移，高血压妊娠疾病以及绝经性雌激素缺乏症或绝经荷尔蒙治疗如何影响女性的脑血管功能和认知。三个个人但相互关联的项目将调查总体主题。项目我将检验以下假设：高血压妊娠疾病的史是全因和心血管死亡率，未来心血管疾病以及通过使用基于人群的方法的认知障碍的危险因素。从罗切斯特流行病学项目（REP）中选择的同类人群将对脑血管反应和认知功能进行前瞻性评估。 II项目将研究雌激素治疗对与更年期早期安慰剂相比接受雌激素治疗的女性认知健康和认知表现的成像标记的神经保护作用。更年期被认为是雌激素治疗的“机会之窗”。该项目利用正在进行的Kronos早期雌激素预防研究（Keeps）的队列。 III项目使用项目I和II中定义的队列将定义脑微血管扩张器电容，表征了血液传播的微覆物和血小板的血小板潜力，并定义了这些特征与脑微血管血管舒张的特征之间的关系，并且大脑结构和认知的变化。行政核心将支持操作和质量控制，临床分析核心将提供标准化的主题招聘，数据 管理和分析所有三个项目。 SCOR对RFA的反应高度敏感，因为它解决了通过生活过渡影响人员的特定性别差异，它整合了临床和基础研究，并且在Mayo Clinic使用了独特的资源。该项目涉及成像和血溶性标记的新型技术方法，以机械地处理疾病过程。此外，定义的基础设施和同伙将为将来的性别差异研究提供基础。通过“基于性别的镜头”查看研究和医疗分娩，并注意个人的性染色体补充和荷尔蒙地位，这是个性化护理的基础。梅奥诊所的性别差异的分数将有助于整个研究和临床企业的健康，疾病和治疗的性决定因素。此外，SCOR调查人员将为特定和一般的国家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个相关条件不成比例地影响其寿命的男女。该跨学科计划将利用创新的工具成像和诊断技术来了解血液供应对大脑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认知。这些研究将确定哪些妇女可能会从早期治疗中受益，以在其生活过渡中维持认知健康。