Midlife Vascular Risk Factors for Alzheimer's Disease in Persons with HFpEF

HFpEF 患者阿尔茨海默病的中年血管危险因素

• 批准号: 10591765
• 负责人: Brittany Butts
• 金额: $ 19.28万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591765
• 关键词: ACE2; Adult; African American; Age; Age Years; Aging; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer' s disease patient; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Biological Markers; Black race; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood capillaries; C-reactive protein; CCL2 gene; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Cerebrospinal Fluid; Cerebrovascular Circulation; Data; Development; Diagnosis; Disease; Disease Progression; EFRAC; Elderly; Enrollment; Essential Hypertension; Functional disorder; Future; Goals; Health Disparities Research; Heart failure; Hematological Disease; High Prevalence; Hypertension; Individual; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-6; Interleukin-9; Intervention; K-Series Research Career Programs; Knowledge; Lead; Left Ventricular Ejection Fraction; Left Ventricular Hypertrophy; Light; Link; Longitudinal Studies; Measures; Memory; Morbidity - disease rate; Not Hispanic or Latino; Participant; Pathogenesis; Pathologic; Pathway interactions; Peptidyl-Dipeptidase A; Pericytes; Persons; Physiologic pulse; Platelet-Derived Growth Factor beta Receptor; Play; Population; Prevalence; Race; Relative Risks; Renin-Angiotensin System; Research; Risk; Risk Reduction; Role; Sampling; Science; Senile Plaques; TNF gene; Testing; Time; Training; Transforming Growth Factors; Vascular Diseases; Visuospatial; abeta accumulation; arterial stiffness; blood-brain barrier disruption; cardiovascular risk factor; career development; cerebral hypoperfusion; clinical trial implementation; cognitive function; cohort; cytokine; endothelial dysfunction; enzyme activity; experience; health disparity; high risk; high risk population; hyperphosphorylated tau; improved; middle age; mortality; neurofibrillary tangle formation; neurofilament; novel; predictive marker; preservation; racial difference; racial diversity; tau Proteins; tau-1; translational research program; vascular risk factor

ABSTRACT The purpose of this study is to determine the extent to which vascular risk factors are associated with biomarkers of Alzheimer’s disease (AD) risk over time in middle aged adults with heart failure with preserved ejection fraction (HFpEF). Mid-life cardiovascular risk factors contribute to the development of AD in later life and to AD progression. Pathophysiologic mechanisms in HFpEF share mechanistic pathways implicated in AD development, such as cerebral hypoperfusion, blood brain barrier (BBB) disruption, systemic and central inflammation, and neurohormonal dysregulation. These AD pathways lead to accumulation of AD biomarkers in cerebral spinal fluid (CSF) and blood. This study will enroll persons with HFpEF to elucidate vascular risk factors specific to this understudied population with pathophysiologic drivers of vascular dysfunction associated with AD risk. The proposed longitudinal study will test the hypothesis that midlife vascular risk factors predict biomarkers of AD risk in persons with HFpEF. We will test the following Specific Aims in a high-risk cohort of 80 non-Hispanic White (n=40) and Black/African American (n=40) individuals during middle age (45-65yrs) who have a diagnosis of HFpEF over 2 years: 1) assess the association of vascular risks with CSF biomarkers of AD risk over two years in middle aged adults with HFpEF, 2) assess the association of vascular risks with blood biomarkers of AD risk over two years in middle aged adults with HFpEF, and 3) assess the association of vascular risks with cognitive function over two years in middle aged adults with HFpEF. This career development award builds on previously developed strengths in studying mechanisms in cardiovascular disease pathophysiology and aims to fill the gap related to Alzheimer’s disease research in the applicant’s training. Specific career development goal included in this plan are: 1) gain expertise in the science of AD and AD biomarkers, including collecting and analyzing AD biomarkers from blood and cerebrospinal fluid and vascular function measures, 2) gain advanced training and experience in cognitive function measures, 3) gain expertise in clinical trial implementation, 4) refine knowledge in health disparities research, and 5) transition to independence and prepare for the next stage of my translational research program. Findings from this study will lead to the identification of pathways that might be amenable to interventions that improve vascular function for persons with HFpEF, with the goal of decreasing AD risk in this high morbidity population.

抽象的 这项研究的目的是确定血管危险因素与之相关的程度 阿尔茨海默氏病的生物标志物（AD）风险随着时间的流逝，心力衰竭保留 射血分数（HFPEF）。中年的心血管危险因素有助于后来的广告发展 并进行广告进展。 HFPEF共享AD中实施的HFPEF共享机械途径的病理生理机制 开发，例如脑部灌注灌注，血脑屏障（BBB）破坏，全身和中央 炎症和神经激素失调。这些AD途径导致AD生物标志物的积累 在脑脊液（CSF）和血液中。这项研究将注册HFPEF的人以阐明血管风险 与血管功能障碍的病理生理驱动因素相关的病理生理驱动因素与该知识的人群有关的因素 有广告风险。拟议的纵向研究将检验中期血管风险因素预测的假设 HFPEF患者的AD风险生物标志物。我们将在高风险队列中测试以下特定目标 80个非西班牙裔白人（n = 40）和黑人/非裔美国人（n = 40）中年（45-65岁） 在2年内诊断为HFPEF的人：1）评估血管风险与CSF生物标志物的关联 在中年成年人患有HFPEF两年的AD风险，2）评估血管风险与 在患有HFPEF的中年成年人的两年内，AD风险的血液生物标志物和3）评估关联 在中年成年人患有HFPEF的两年内，具有认知功能的血管风险。这个职业 开发奖基于以前在研究心血管中的机制方面的优势 疾病的病理生理学，旨在填补与申请人的阿尔茨海默氏病研究有关的空白 训练。本计划中包括的具体职业发展目标是：1）在广告科学方面获得专业知识 AD生物标志物，包括从血液和脑脊液中收集和分析AD生物标志物以及 血管功能度量，2）获得认知功能度量的高级培训和经验，3）增益 临床试验实施方面的专业知识，4）完善健康差异研究知识，5）过渡到 独立并为我的翻译研究计划的下一阶段做准备。这项研究的结果 将导致识别可能适合改善血管的干预措施的途径 HFPEF患者的功能，目的是在这种高发病率中降低AD风险。