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: 10182419
• 负责人: Lyndsay Anne Harshman
• 金额: $ 30.63万
• 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/10182419
• 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; burden of illness; cognitive performance; cohort; congenital anomaly; 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 儿童慢性肾脏病（pCKD）最常见的原因是肾脏和泌尿道的先天性异常;因此，这意味着终身疾病。即使患有轻度CKD的儿童也存在神经认知困难的风险，这些神经认知困难具体表现为注意力调节、学业成绩不良和执行功能[1-3]。神经认知缺陷对生活质量有广泛的影响，因为它们导致成人CKD人群的高中毕业率较低和长期就业不足[4]。pCKD的认知并发症被认为是异常“肾-脑轴”的后遗症，肾损害和相关疾病后遗症可能对大脑产生负面影响，导致pCKD进展过程中认知损害风险增加[5-7]。然而，在pCKD的背景下，我们对发育中的大脑的理解存在着关键的差距。因此，本提案的总体目标是使用MRI和认知/行为评估量化轻度至中度（早期）CKD pCKD参与者与未受影响对照组相比的结构和功能性脑差异。据我们所知，这是世界上第一个使用磁共振成像（MRI）定量评估早期pCKD幼儿大脑的建议。来自我们实验室的初步数据是惊人的，并证明了与健康同龄人相比，患有先天性非肾小球原因CKD的儿童的大脑结构差异（特别是小脑内）。小脑体积减小和肾功能受损之间似乎有直接关系。此外，较低的小脑灰质体积似乎可以预测CKD儿童执行功能特定的神经认知任务的表现。我们的试验数据表明，pCKD中的异常静息状态连接，CKD儿童显示小脑（齿状核）和额叶皮质之间的连接不足。我们将研究疾病负担对轻度/中度CKD儿童神经发育的“剂量”效应。了解pCKD进展和严重程度对发育中的大脑的影响将有助于提高对疾病进展对儿童期神经发育结局的作用的认识，并为整个CKD生命周期的患者护理提供新的方法。