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; 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.

项目摘要/摘要 这个受过指导的注重患者的研究职业发展奖（K23）的目的是 支持我定量表征儿童大脑结构和功能的短期职业目标 使用磁共振成像（MRI）轻度至中度慢性肾脏疾病（CKD）。超过50％ 小儿CKD病例是由于先天性（结构）异常引起的，因此，诊断预示了生命 - 长期诊断需要常规护理。小儿CKD肾脏下降的特征包括代谢性酸中毒， 心血管疾病，生长差和贫血 - 所有这些都可能具有有害的多因素影响 在发育中的大脑上。这是一个自然的扩展，患有高级CKD的儿童有神经认知的风险 衰退。特别是，尽管智力（IQ）通常是完整的，但CKD的儿童在 执行职能和学术成就。神经影像学研究使用了异质样品 （包括末期肾脏疾病）依赖计算机断层扫描。没有出版的儿科研究 已经应用了定量的结构或功能性神经影像学技术。我们将量化结构和白色 在小儿CKD中使用MRI的物质大脑差异 与健康对照相比；这将是第一个利用功能性MRI序列来表征大脑的研究 pH是与CKD相关的代谢疾病的代理。该研究将使用神经认知和实验室评估 结合小儿CKD种群中脑结构和功能的神经影像学相关。我们的 基于初步数据的假设可以预测体积和白质差异将在 CKD参与者的小脑。这些差异将涉及整体皮质 - 丘脑 - 脑脑白色 与执行功能相关的物质区域。我们将研究伯恩疾病对疾病的“剂量”影响 小脑体积和白质的发育是通过评估轻度儿童的横截面队列 与健康对照相比，中等CKD。了解小儿CKD的影响 发育中的大脑的进展和严重程度将使人们对疾病作用的认识提高 在儿童时期的神经发育结果和 为CKD寿命提供新的治疗方法和患者教育方法。我的临床工作 儿科肾脏病和引言与神经影像学的工作为实现这些奠定了坚实的基础 目标。在复杂的神经影像学方法，神经发育和统计数据中，需要进一步培训。 拟议的综合研究，指导和教学培训计划以及杰出的 爱荷华大学的研究环境和儿童医院教师的现场心态 费城，将培养我的长期职业目标，成为研究大脑的独立研究者 小儿CKD的结构和功能。