Pediatric Ambulatory Blood Pressure Trajectory and Brain Health in Midlife

摘要 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。 尽管几十年的研究已经确定了认知能力下降和痴呆症的多种风险因素， 不清楚什么时候在生命周期中，以及为谁，预防和干预计划应该是 切实贯彻有人认为，认知功能受损可能是一种从中年开始的临床沉默性疾病 或者更早，可能有一个根延伸到早期的生活。这与高血压特别相关， 这不仅是因为高血压被认为是痴呆症的一个重要的可改变的危险因素， 认知功能障碍，而且在儿科中血压升高（BP）的患病率一直是 在全球范围内增加。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，以保证高血压儿童的认知或大脑健康标志物的治疗效果。 该项目的目标是解开生命早期血压升高对大脑的长期影响 结构和认知功能。这将通过利用格鲁吉亚压力和心脏来实现 研究对象为600多名儿童（49%为黑人，50%为女性），他们在23年内接受了多达16次的测量。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硬化的措施。本课题 将使用磁共振成像（MRI）（包括动脉）对这些受试者进行额外随访 自旋标记（ASL）灌注和脑扩散张量成像（DTI））和神经认知测试。具体 目的1：检查（a）在生命早期，血压水平升高和/或血压升高是否随时间而增加 与脑灌注和脑结构改变以及中年认知功能受损有关， (b)这种影响在什么年龄开始发生（例如，童年或青年）。目标2：审查是否 动脉僵硬度和动脉粥样硬化的进展（通过脉搏波速度和颈动脉内膜-中膜评估 （a）在生命早期的多次访问中测量的厚度）有助于脑功能和结构偏差，以及 （B）至少部分介导生命早期血压升高对认知功能的影响， 大脑和认知健康受损。目的3：检查慢性压力和/或相关不利因素是否 行为与血压升高相互作用，并加重对血管，大脑和认知健康的不利影响。 第二个目的是探讨这些关系是否受到种族和性别的调节。

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.