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: 10165457
• 负责人: Priya Palta
• 金额: $ 155.49万
• 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/10165457
• 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 Groups; National Institute on Aging; Nerve Degeneration; Outcome; Participant; Pathology; Phenotype; Plasma; 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; blood pressure variability; 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.

项目摘要/摘要 在非裔美国人中，轻度认知障碍(MCI)和痴呆症的发病率高出两到三倍 (AAS)比白人老年人更多。观察性和临床试验数据，最近一次来自心脏收缩 血压干预试验：降低高血压患者的记忆和认知(Sprint-Mind)，支持 血压是MCI和痴呆症最重要的可改变的血管危险因素。然而， 在Sprint-Mind中的随访持续时间较短，同时未能检测到以下方面的统计显著好处 偶发痴呆症的较低血压目标意味着需要更长期的观察数据。 以充分解决临床试验结果的影响。这些问题对于美国律师协会来说尤其突出，他们 高血压发病较早，患痴呆症的风险较高，尤其是脑血管疾病 病理学。即使在考虑了种族/民族在血压水平上的差异后，潜在的机制 患痴呆症风险的种族差异还没有得到很好的理解。此外，尽管面临着很高的负担， 血压，有些人是有韧性的，取得了比预期更好的结果。具体因素 有助于大脑健康韧性的因素还没有得到很好的确立。我们建议解决这些研究差距 在一项针对杰克逊心脏研究(JHS)约2700名参与者的2020-2022年第4次检查的辅助研究中， 一项正在进行的对具有良好特征的AA的队列研究。JHS考试4将包括脑部磁共振 磁共振成像(MRI)数据，以确定脑血管疾病和神经变性。我们建议增加 足以对MCI和痴呆症进行分类的认知和功能指标以及创新的血浆 淀粉样蛋白(AB42、AB40)、tau和神经变性(神经丝光)的生物标记物。其主要目标是 如下：目标1.估计长期暴露于20年时间加权平均高值的关系 血压和血压负荷对(1)认知表现；(2)MCI和痴呆的患病率；(3) 脑血管疾病和神经退行性变的标记物由MRI量化；以及(4)血浆淀粉样蛋白tau 和神经退化。目标2.检查性别、教育质量(即阅读水平)是否 WRAT)、APOE-e4和ABCA7基因改变了长期接触高血压病患者的相关性 血压和血压与认知结果有关。这项研究是对PAR-19-070的回应，而不是- AG-18-047(健康差异和阿尔茨海默病)：在地标建筑上增加认知评估 AAS心血管疾病的队列研究；利用现有和新的数据来了解风险和 认知障碍的弹性因素；并利用JHS队列来了解血管机制 少数民族人群潜在的认知障碍。这项研究也是在 更新的国家老龄/阿尔茨海默氏症协会研究框架，其中构建了 淀粉样蛋白、tau蛋白和神经退行性变是突出的特征。最后，这项研究的结果将为未来提供参考 研究并对旨在改善少数族裔人口脑老化的政策产生影响。