Cognitive Profiles and Neuroimaging Correlates in Mild to Moderate Pediatric Chronic Kidney Disease

认知特征和神经影像学与轻度至中度小儿慢性肾脏病相关

• 批准号: 9162944
• 负责人: Lyndsay Anne Harshman
• 金额: $ 14.61万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9162944
• 关键词: Academic achievement; Anemia; Awareness; Behavior; Behavior assessment; Bicarbonates; Brain; Cardiovascular Diseases; Cerebellum; Child; Childhood; Chronic Kidney Failure; Clinical; Cognitive; Cognitive deficits; Complex; Data; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Early Diagnosis; End stage renal failure; Environment; Faculty; Fostering; Foundations; Functional Magnetic Resonance Imaging; Future; Glomerular Filtration Rate; Goals; Graduation Rates; Growth; Image; Intelligence; Intervention; Iowa; Kidney; Laboratories; Lead; Life; Link; Longevity; Magnetic Resonance Imaging; Measures; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Metabolic Diseases; Metabolic acidosis; Metabolism; Methods; Nephrology; Neurocognitive; Neurocognitive Deficit; Normal Range; Outcome; PTH gene; Participant; Patient Education; Patients; Pediatric Hospitals; Performance; Philadelphia; Play; Population; Prevention; Process; Proxy; Publishing; Renal function; Research; Research Personnel; Risk; Role; Sampling; Serum; Severities; Site; Solid; Specificity; Structural Congenital Anomalies; Structural defect; Structure; System; Techniques; Thalamic structure; Training; Training Programs; Underachievement; Underemployment; Universities; Ursidae Family; Vitamin D; Work; X-Ray Computed Tomography; abstracting; base; boys; brain metabolism; burden of illness; career; cognitive function; cognitive task; cohort; dosage; driving force; emotion regulation; executive function; externalizing behavior; frontal lobe; high school; improved; motor control; neurodevelopment; neuroimaging; novel; novel strategies; pediatric patients; rho; routine care; statistics; white matter

Project Summary/Abstract The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) application is to support my short-term career objective of quantitatively characterizing brain structure and function in children with mild to moderate chronic kidney disease (CKD) using magnetic resonance imaging (MRI). Over 50% of all cases of pediatric CKD are due to congenital (structural) anomalies, and as such, the diagnosis portends a life- long diagnosis requiring routine care. Features of renal decline in pediatric CKD include metabolic acidosis, cardiovascular disease, poor growth, and anemia—all of which may have a deleterious, multifactorial impact on the developing brain. It is a natural extension that children with advanced CKD are at risk for neurocognitive decline. Specifically, despite generally intact intelligence (IQ), children with CKD demonstrate deficits in executive function and academic achievement. Neuroimaging research has utilized heterogenous samples (including end-stage renal disease) with reliance on computerized tomography. No published pediatric studies have applied quantitative structural or functional neuroimaging techniques. We will quantify structural and white matter brain differences using MRI in pediatric CKD patients with mild to moderate, non-glomerular CKD compared to healthy controls; it will be the first study to utilize functional MRI sequences to characterize brain pH as a proxy of CKD-related metabolic disease. The study will use neurocognitive and laboratory assessment in conjunction with neuroimaging correlates of brain structure and function in the pediatric CKD population. Our hypotheses, based on preliminary data, predict volumetric and white matter differences will be observed in the cerebellums of CKD participants. These differences will involve integral cortico-thalamic-cerebellar white matter tracts associated with executive function. We will investigate a “dosage” effect of disease burden on cerebellar volume and white matter development by evaluating a cross-sectional cohort of children with mild to moderate CKD in comparison to healthy controls. Understanding the influence of pediatric CKD progression and severity on the developing brain will allow enhanced awareness of the role of disease progression, specifically metabolic disease, on neurodevelopmental outcomes in childhood and inform new approaches to treatment and patient education across the CKD lifespan. My clinical work in pediatric nephrology and introductory work with neuroimaging have laid a solid foundation for achieving these goals. Further training is necessary in sophisticated neuroimaging methods, neurodevelopment, and statistics. The proposed integrated research, mentorship, and didactic training programs, combined with the outstanding research environment at the University of Iowa and off-site mentorship from faculty at Children's Hospital of Philadelphia, will foster my long-term career objective to be an independent investigator studying brain structure and function in pediatric CKD.

项目概要/摘要 此指导性患者导向研究职业发展奖 (K23) 申请的目的是 支持我定量描述儿童大脑结构和功能的短期职业目标 使用磁共振成像 (MRI) 诊断轻度至中度慢性肾脏病 (CKD)。超过全部的50% 儿童 CKD 病例是由于先天性（结构性）异常造成的，因此，诊断预示着生命- 长期诊断需要常规护理。儿童 CKD 肾功能衰退的特征包括代谢性酸中毒、 心血管疾病、生长不良和贫血——所有这些都可能产生有害的多因素影响 关于发育中的大脑。患有晚期 CKD 的儿童面临神经认知障碍的风险是自然的延伸 衰退。具体来说，尽管患有 CKD 的儿童智力 (IQ) 总体上完好，但他们在智力方面却表现出缺陷。 执行功能和学术成就。神经影像研究利用了异质样本 （包括终末期肾病）依赖计算机断层扫描。尚未发表儿科研究 应用了定量结构或功能神经影像技术。我们将量化结构和白色 使用 MRI 研究轻度至中度非肾小球 CKD 儿童 CKD 患者的物质脑差异 与健康对照组相比；这将是第一项利用功能性 MRI 序列来表征大脑的研究 pH 作为 CKD 相关代谢疾病的指标。该研究将使用神经认知和实验室评估 结合神经影像学研究儿童 CKD 人群大脑结构和功能的相关性。我们的 根据初步数据，预测体积和白质差异将在 CKD 参与者的小脑。这些差异将涉及完整的皮质-丘脑-小脑白 与执行功能相关的物质束。我们将研究疾病负担对“剂量”的影响 通过评估轻度至轻度儿童的横断面队列来评估小脑体积和白质发育 与健康对照相比，患有中度 CKD。了解儿童 CKD 的影响 发育中大脑的进展和严重程度将增强人们对疾病作用的认识 进展，特别是代谢疾病，对儿童时期神经发育结果的影响 为整个 CKD 生命周期的治疗和患者教育提供新方法。我的临床工作 儿科肾脏病学和神经影像学的入门工作为实现这些目标奠定了坚实的基础 目标。复杂的神经影像方法、神经发育和统计学方面的进一步培训是必要的。 拟议的综合研究、指导和教学培训计划，结合杰出的 爱荷华大学的研究环境以及来自爱荷华州儿童医院教员的场外指导 费城，将培养我的长期职业目标，成为一名研究大脑的独立研究者 儿科 CKD 的结构和功能。