Blood Pressure and ADRD in African Americans: the Jackson Heart Study

非裔美国人的血压和 ADRD：杰克逊心脏研究

• 批准号: 9891658
• 负责人: Priya Palta
• 金额: $ 157.42万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891658
• 关键词: Address; African American; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Ambulatory Blood Pressure Monitoring; American Heart Association; Amyloid; Ancillary Study; Biological Factors; Biological Markers; Blood Pressure; Blood Vessels; Brain; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; Classification; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Complement; Coupled; Data; Dementia; Detection; Diagnosis; Diastolic blood pressure; Elderly; Exposure to; Failure; Genetic; Genotype; Goals; Guidelines; High Prevalence; Hour; Hypertension; Impaired cognition; Individual; Intervention Trial; Jackson Heart Study; Joints; Light; Magnetic Resonance Imaging; Measures; Mediating; Mediator of activation protein; Memory; Minority; National Institute on Aging; Nerve Degeneration; Outcome; Participant; Pathology; Phenotype; Plasma; Population; Population Heterogeneity; Prevalence; Prevention; Race; Reading; Recommendation; Reporting; Research; Risk; Role; Specific qualifier value; Time; Update; White Matter Hyperintensity; Woman; adjudication; aging brain; apolipoprotein E-4; blood pressure intervention; blood pressure reduction; brain health; brain volume; cerebrovascular pathology; cognitive function; cognitive performance; cognitive testing; cohort; college; dementia risk; early onset; ethnic difference; follow-up; genetic risk factor; genetic variant; health disparity; high risk; improved; innovation; meetings; member; mild cognitive impairment; minority health; neurofilament; neuropathology; novel; policy implication; primary outcome; racial disparity; resilience; response; secondary outcome; sex; social health determinants; symposium; tau Proteins; vascular risk factor

PROJECT SUMMARY/ABSTRACT Rates of mild cognitive impairment (MCI) and dementia are two to three times higher among African Americans (AAs) than among White older adults. Observational and clinical trial data, most recently from the Systolic Blood Pressure Intervention Trial: Memory and Cognition in Decreased Hypertension (SPRINT-MIND), support that blood pressure is the most important modifiable vascular risk factor for MCI and dementia. However, the short duration of follow-up in SPRINT-MIND coupled with the failure to detect a statistically significant benefit of a lower blood pressure goal for incident dementia means that longer-term observational data will be necessary to fully address the implications of the clinical trial results. These questions are particularly salient for AAs, who have earlier onset of high blood pressure and are at higher risk of dementia, in particular cerebrovascular pathology. Even after considering race/ethnic differences in blood pressure level, the mechanisms underlying racial disparities in risk for dementia are not well understood. Additionally, despite facing a high burden of high blood pressure, some individuals are resilient, achieving better-than-expected outcomes. The specific factors that contribute to brain-health resilience are not well established. We propose to address these research gaps in an ancillary study to the 2020-2022 4th examination of ~2,700 participants in the Jackson Heart Study (JHS), an ongoing cohort study of well-characterized AAs. The JHS Exam 4 will include brain magnetic resonance imaging (MRI) data to ascertain cerebrovascular disease and neurodegeneration. We propose to add measures of cognition and function sufficient for classification of MCI and dementia, and innovative plasma biomarkers of amyloid (Ab42, Ab40), tau, and neurodegeneration (neurofilament light). The primary aims are as follows: Aim 1. Estimate the long-term associations of exposure to high 20-year time-weighted average blood pressure and blood pressure load on (1) cognitive performance; (2) prevalence of MCI and dementia; (3) markers of cerebrovascular disease and neurodegeneration quantified from MRI; and (4) plasma amyloid, tau and neurodegeneration. Aim 2. Examine whether sex, educational quality (i.e. reading level measured with the WRAT), and APOE-e4 and ABCA7 genotype, modify the associations of long-term exposure to high blood pressure and blood pressure load with cognitive outcomes. This study is responsive to PAR-19-070 and NOT- AG-18-047 (Health Disparities and Alzheimer’s Disease) by adding cognitive assessments to a landmark cohort study of cardiovascular disease in AAs; leveraging existing and new data to understand risk and resilience factors for cognitive impairment; and drawing on the JHS cohort to understand vascular mechanisms underlying cognitive impairment in a minority population. This study is also proposed in the context of the updated National Institute on Aging/Alzheimer’s Association research framework in which the constructs of amyloid, tau, and neurodegeneration are featured prominently. Lastly, results from this study will inform future research and have implications for policies intended to improve brain aging in minority populations.

项目总结/摘要 轻度认知障碍（MCI）和痴呆症的发生率在非洲裔美国人中高出两到三倍 (AAs)而不是白色老年人。观察性和临床试验数据，最近来自于Syphilis 血压干预试验：记忆和认知降低高血压（SPRINT-MIND），支持 血压是MCI和痴呆最重要的可改变的血管危险因素。但 SPRINT-MIND的随访时间短，且未能检测到以下方面的统计学显著获益： 降低痴呆症发病率的血压目标意味着需要长期的观察数据 以充分解决临床试验结果的影响。这些问题对认可机构尤其重要， 较早出现高血压，患痴呆症的风险较高，特别是脑血管疾病 病理即使考虑到血压水平的种族/民族差异， 痴呆症风险的种族差异还没有得到很好的理解。此外，尽管面临着沉重的负担， 尽管血压下降，但有些人很有弹性，取得了好于预期的结果。的具体因素 对大脑健康恢复力有贡献的因素还没有很好地建立起来。我们建议填补这些研究空白 在杰克逊心脏研究（JHS）2020-2022年第4次检查约2,700名参与者的辅助研究中， 一项正在进行的特征明确的AA队列研究。JHS考试4将包括脑磁共振 成像（MRI）数据，以确定脑血管疾病和神经变性。我们建议加入 足以对MCI和痴呆进行分类的认知和功能测量，以及创新的血浆 淀粉样蛋白（Ab 42，Ab 40），tau和神经变性（神经丝光）的生物标志物。主要目标是 具体如下：目标1。估计暴露于高20年时间加权平均值的长期关联 血压和血压负荷对（1）认知能力;（2）MCI和痴呆的患病率;（3） 从MRI定量的脑血管疾病和神经变性的标志物;和（4）血浆淀粉样蛋白，tau 和神经退化目标二。检查性别、教育质量（即用 WRAT），APOE-e4和ABCA 7基因型，改变了长期暴露于高血压的相关性。 血压和血压负荷与认知结果的关系。本研究响应PAR-19-070，而非- AG-18-047（健康差异和阿尔茨海默病），将认知评估添加到里程碑 AA中心血管疾病的队列研究;利用现有和新数据了解风险和 认知障碍的弹性因素;并利用JHS队列来了解血管机制 在少数民族人群中存在潜在的认知障碍。这项研究也是在《公约》的背景下提出的。 更新的国家老龄化研究所/阿尔茨海默氏症协会研究框架，其中的结构， 淀粉样蛋白、tau蛋白和神经变性是显著特征。最后，这项研究的结果将为未来提供信息。 研究并对旨在改善少数群体大脑老化的政策产生影响。