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令人恐惧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，但它仍然 不清楚什么时候应该在生命周期内，针对谁，预防和干预计划应该是 实施。已有研究表明，认知障碍可能是一种临床上始于中年的静默障碍。 或者甚至更早，并且可能有一个可以追溯到早期生命的根。这与高血压尤其相关， 不仅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，而且 认知障碍，但在儿科中高血压(BP)的流行率也一直是 在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。 检查高血压儿童对认知或脑健康标志物的治疗效果。 这个项目的目标是理清早期血压升高对大脑的长期影响。 中年的结构和认知功能。这将通过利用佐治亚州的压力和心脏来实现 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年里被测量了16次。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的测量。在这个项目中，我们 将使用磁共振成像(MRI)(包括动脉)对这些受试者进行额外的随访 自旋标记(ASL)灌注和脑扩散张量成像(DTI))和神经认知测试。具体的 目标是：Aim1：检查(A)早期血压水平升高和/或更大的血压是否随时间增加 与中年的脑血流和脑结构改变以及认知功能受损有关，以及 (B)这种影响在什么年龄开始发生(例如，童年或青壮年)。AIM2：检查是否 动脉僵硬和动脉粥样硬化的进展(通过脉搏波速度和颈动脉内膜-中层来评估 在早期生活中(A)导致大脑功能和结构偏差，以及 中年时的认知障碍，以及(B)至少部分地调节了早期血压升高对 大脑受损和认知健康。目的：检查慢性应激和/或相关的不利因素 行为与血压升高相互作用，并加剧了对血管、大脑和认知健康的不利影响。 第二个目标是探索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.