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.

项目概要 儿童慢性肾病 (pCKD) 最常见的原因是肾脏和泌尿道先天性异常；因此，即使患有轻度 CKD 的儿童也面临着注意力调节、学业成绩不佳和执行力方面的神经认知困难的风险。神经认知缺陷对生活质量具有广泛影响，因为它们会导致成人 CKD 患者高中毕业率较低和长期就业不足。 pCKD 的认知并发症被认为是“肾脑轴”异常的后遗症，其中肾脏损伤和相关疾病后遗症可能会对大脑产生负面影响，导致 pCKD 进展过程中认知障碍的风险增加。 [5-7]. 然而，我们对 pCKD 背景下大脑发育的理解存在重大差距，因此，该提案的首要目标是使用 MRI 和认知/行为评估来量化大脑的结构和功能差异。患有轻度至中度（早期）CKD 的 pCKD 参与者与未受影响的对照组相比，据我们所知，该提案是世界上第一个利用磁共振成像对患有早期 pCKD 的幼儿的大脑进行定量评估的项目。我们实验室的初步数据令人震惊，表明患有先天性、非肾小球原因的 CKD 儿童与健康同龄人相比，存在显着的大脑结构差异（尤其是小脑内）。小脑体积减少与肾功能受损之间存在直接关系，此外，小脑灰质体积降低似乎可以预测 CKD 儿童执行功能特有的神经认知任务的表现。 CKD 显示小脑（齿状核）和额叶皮质之间的连接性低下。我们将研究疾病负担对轻度/中度儿童神经发育的“剂量”影响。 CKD：了解 pCKD 进展和严重程度对发育中大脑的影响将有助于提高人们对疾病进展对儿童神经发育结果的作用的认识，并为整个 CKD 生命周期的患者护理提供新方法。