Brain anatomical imaging and neurocognition in pediatric kidney disease (BRAIN KID)

小儿肾脏疾病的脑解剖成像和神经认知（BRAIN KID）

• 批准号: 10398932
• 负责人: Lyndsay Anne Harshman
• 金额: $ 30.58万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10398932
• 关键词: Academic achievement; Acidosis; Address; Adolescent; Adult; Age; Attention; Awareness; Behavior; Behavior assessment; Biological Markers; Brain; Cerebellum; Child; Childhood; Chronic Kidney Failure; Cognition; Cognitive; Corpus Callosum; Data; Dentate nucleus; Development; Dialysis procedure; Disease; Disease Progression; Etiology; Glomerular Filtration Rate; Goals; Graduation Rates; Hypertension; Image; Impaired cognition; Impairment; Intelligence; Kidney; Kidney Diseases; Laboratories; Link; Longevity; Magnetic Resonance Imaging; Measures; Metabolism; National Institute of Diabetes and Digestive and Kidney Diseases; Neurocognition; Neurocognitive; Neurocognitive Deficit; Outcome; Participant; Patient Care; Patients; Performance; Pontine structure; Population; Publishing; Quality of life; Regulation; Renal function; Research; Research Proposals; Rest; Risk; Risk Factors; Role; School-Age Population; Severity of illness; Signal Transduction; Structure; Suggestion; Testing; Transplantation; Underachievement; Underemployment; Uremia; Urinary tract; anatomic imaging; brain abnormalities; brain magnetic resonance imaging; burden of illness; cognitive performance; cohort; congenital anomalies of the kidney; dosage; executive function; frontal lobe; gray matter; high school; improved; neurodevelopment; neuroimaging; novel; novel strategies; pediatric patients; peer; rho; white matter

Project Summary Pediatric chronic kidney disease (pCKD) is most commonly due to congenital anomalies of the kidney and urinary tract; thus, meaning a lifetime of disease. Children with even mild CKD are at risk for neurocognitive difficulties specific to attention regulation, academic underachievement, and executive function [1-3]. Neurocognitive deficits have broad implication on quality of life, as they contribute to poorer high school graduation rates and long-term underemployment in the adult CKD population [4]. The cognitive complications of pCKD are thought to represent sequelae of an aberrant “kidney-brain axis” whereby kidney impairment and associated disease sequelae may negatively impact the brain, leading to increased risk of cognitive impairment in the course of pCKD progression [5-7]. However, there is a critical gap in our understanding of the developing brain in the context of pCKD. Thus, the overarching goal of this proposal is to quantify structural and functional brain differences using MRI and cognitive/behavioral assessments in pCKD participants with mild to moderate (early) CKD compared to unaffected controls. To our knowledge, this proposal is the first in the world to quantitatively evaluate the brain in young children with early stage pCKD due to a focused disease etiology using magnetic resonance imaging (MRI). Preliminary data from our laboratory are striking and demonstrate robust structural brain differences (particularly within the cerebellum) in children with congenital, non-glomerular causes of CKD compared to healthy peers. There appears to be a direct relationship between decreased cerebellum volume and impaired kidney function. Furthermore, lower cerebellum gray matter volume appears to predict performance on neurocognitive tasks specific to executive function in children with CKD. Our pilot data demonstrate abnormal resting state connectivity in pCKD whereby children with CKD show hypo-connectivity between the cerebellum (dentate nucleus) and the frontal cortices. We will investigate a “dosage” effect of disease burden on neurodevelopment in children with mild/moderate CKD. Understanding the influence of pCKD progression and severity on the developing brain will allow enhanced awareness of the role of disease progression on neurodevelopmental outcomes in childhood and inform new approaches to patient care across the CKD lifespan.

项目摘要 小儿慢性肾脏疾病（PCKD）最常见的是肾脏和尿路的先天异常。因此，意味着疾病的生命。即使是轻度CKD的儿童也有针对注意力调节，学术成就和执行功能的神经认知难度的风险[1-3]。神经认知的定义对生活质量具有广泛的影响，因为它们导致了成人CKD人群的高中毕业率和长期就业不足[4]。 PCKD的认知并发症被认为代表了异常“肾脑轴”的后遗症，从而肾脏障碍和相关疾病后遗症可能会对大脑产生负面影响，从而导致PCKD进展过程中认知障碍的风险增加[5-7]。但是，在PCKD背景下，我们对发展中大脑的理解存在一个危险的差距。这是该提案的总体目标是使用MRI和认知/行为评估在PCKD参与者中使用轻度至中度（早期）CKD的参与者进行量化结构和功能性大脑差异，与不受影响的对照组相比。据我们所知，该提案是世界上第一个通过使用磁共振成像（MRI）的重点疾病远程学（MRI）来定量评估早期PCKD幼儿大脑的大脑。与健康的同龄人相比，我们实验室的初步数据正在引人注目并证明了先天性，非胶质细胞原因的儿童的鲁棒结构脑差异（部分在小脑内）。小脑体积下降和肾功能受损之间似乎存在直接关系。此外，较低的小脑灰质体积似乎可以预测CKD儿童执行功能的神经认知任务的表现。我们的试点数据表明，PCKD中的静息状态异常，其中CKD儿童在小脑（齿状核）和额叶皮层之间表现出不受欢迎的连接性。我们将研究疾病燃烧对轻度/中度CKD儿童神经发育的“剂量”影响。了解PCKD的进展和严重程度对发育中的大脑的影响将使人们对疾病进展对儿童神经发育结果的作用的认识提高，并为整个CKD寿命的新方法提供新的方法。