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Pediatric Ambulatory Blood Pressure Trajectory and Brain Health in Midlife

中年儿童动态血压轨迹与大脑健康

基本信息

批准号：
10409546
负责人：
JENNIFER E MCDOWELL
金额：
$ 69.17万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10409546
关键词：
Adult Adverse effects Age Aging Alcohol abuse Atherosclerosis Back Behavior Blood Pressure Blood Vessels Brain Carotid Atherosclerotic Disease Cerebrovascular Circulation Cerebrum Child Childhood Chronic Chronic stress Clinical Cognition Cognitive Data Dementia Development Diffusion Magnetic Resonance Imaging Disease Elderly Ethnic Origin Executive Dysfunction Female Fright Gender Goals Health Heart Height Hour Hypertension Impaired cognition Life Life Style Link Longevity Magnetic Resonance Imaging Measurement Measures Mediating Organ Pattern Pediatrics Performance Perfusion Physiologic pulse Plant Roots Population Prevalence Prevention program Process Psychosocial Stress Research Risk Behaviors Risk Factors Smoking Stress Structure Substance abuse problem Time Vascular Diseases Vascular blood supply Visit Youth arterial spin labeling arterial stiffness base blood pressure elevation brain dysfunction brain health carotid intima-media thickness cognitive function cohort dementia risk ethnic difference executive function follow-up gender difference hypertensive intervention program middle age modifiable risk multi-ethnic neurocognitive test normotensive novel physical inactivity preventive intervention prospective treatment effect white matter young adult

项目摘要

ABSTRACT Loss of cognitive function is one of the most feared and devastating manifestations of aging and vascular disease. Although decades of research have identified multiple risk factors for cognitive decline and dementia, it remains unclear when in the lifespan, and for whom, prevention and intervention programs should be implemented. It has been suggested that impaired cognition could be a clinically silent disorder starting in midlife or even earlier, and may have a root extending back into early life. This is particularly relevant to hypertension, not only because hypertension has been recognized as an important modifiable risk factor for dementia and cognitive impairment, but also the prevalence of elevated blood pressure (BP) among pediatrics has been increasing worldwide. However, currently there is not enough evidence linking early life BP to midlife brain function to warrant examining treatment effects in hypertensive children on cognition or markers of brain health. The goal of this project is to disentangle the long-term impact of elevated BP in early life on brain structure and cognitive function in midlife. This will be achieved by utilizing the Georgia Stress and Heart study of over 600 children (49% black and 50% females) who were measured up to 16 times in 23 years. We have collected comprehensive data from childhood to adulthood, including 24-hour ambulatory BP (ABP), chronic stress and behaviors, as well as measures of atherosclerosis and arterial stiffness. In this project, we will conduct an additional follow-up of these subjects using magnetic resonance imaging (MRI) (including arterial spin labeling (ASL) perfusion and brain diffusion tensor imaging (DTI)), and neurocognitive testing. The specific aims are: Aim1: To examine (a) whether elevated BP levels and/or greater BP increases over time in early life are associated with altered cerebral perfusion and brain structure, and impaired cognitive function in midlife, and (b) at what age this impact starts to occur (e.g. childhood or young adulthood). Aim2: To examine whether progression of arterial stiffness and atherosclerosis (assessed by pulse wave velocity and carotid intima-media thickness measured in multiple visits) in early life (a) contributes to brain functional and structural deviation, and cognitive impairment in midlife, and (b) at least partially mediates the impact of elevated BP in early life on impaired brain and cognitive health. Aim3: To examine whether chronic stress and/or related unfavorable behaviors interact with elevated BP, and accentuate the adverse impacts on vascular, brain and cognitive health. The secondary aim is to explore whether these relationships are moderated by ethnicity and gender.

抽象的认知功能丧失是衰老和血管疾病最可怕和最具破坏性的表现之一。尽管数十年的研究已经确定了认知能力下降和痴呆的多种危险因素，但它仍然存在不清楚应在生命周期的何时以及针对谁实施预防和干预计划实施的。有人认为，认知受损可能是一种从中年开始的临床无症状疾病甚至更早，并且可能有一个根源可以追溯到早期生活。这与高血压尤其相关，不仅因为高血压已被认为是痴呆症的一个重要的可改变危险因素，认知障碍，以及儿科中血压升高（BP）的患病率全球范围内不断增加。然而，目前还没有足够的证据将早期血压与中年大脑联系起来功能以保证检查高血压儿童的治疗效果对认知或大脑健康标志的影响。该项目的目标是阐明生命早期血压升高对大脑的长期影响中年的结构和认知功能。这将通过利用乔治亚压力和心脏来实现这项研究对 600 多名儿童（49% 是黑人，50% 是女性）进行了研究，他们在 23 年内接受了多达 16 次测量。我们收集了从儿童到成年的全面数据，包括24小时动态血压（ABP），慢性压力和行为，以及动脉粥样硬化和动脉僵硬度的测量。在这个项目中，我们将使用磁共振成像（MRI）（包括动脉自旋标记（ASL）灌注和脑扩散张量成像（DTI））以及神经认知测试。具体的目标是：目标 1：检查 (a) 血压水平升高和/或血压升高是否会随着生命早期的时间而增加与脑灌注和大脑结构改变以及中年认知功能受损有关，并且 (b) 这种影响在什么年龄开始发生（例如童年或成年初期）。目标2：检查是否动脉硬化和动脉粥样硬化的进展（通过脉搏波速度和颈动脉内膜中层评估 (a) 导致大脑功能和结构偏差，以及中年认知障碍，以及（b）至少部分介导早年血压升高对大脑和认知健康受损。目标 3：检查是否存在慢性压力和/或相关不利因素行为与血压升高相互作用，并加剧对血管、大脑和认知健康的不利影响。第二个目标是探讨这些关系是否受到种族和性别的调节。