Cerebral Impact of Childhood Sleep Apnea

描述（由申请人提供）：儿童阻塞性睡眠呼吸暂停（OSA）的患病率为2- 3%，但儿童睡眠障碍的后果还远未得到充分研究。警觉性、执行功能和运动协调的认知减退与成人OSA相关;重要的是，这些缺陷中的一些是治疗不可逆的。磁共振波谱成像（MRSI）显示的脑损伤已显示在成人OSA。目前尚不清楚发育中的大脑是否有能力避免OSA损伤后的永久性损伤，以及神经元的变化是否发生在早期。为了回答这些问题，我们通过一般临床研究中心的资源，与约翰霍普金斯大学的研究人员开展了一个多学科合作的项目。我们的初步研究结果发表在《公共科学图书馆医学》上，为儿童OSA与神经心理功能障碍有关提供了强有力的证据。此外，使用MRSI，我们证明了一个新的发现，神经元损伤的大脑区域的学习和记忆的OSA儿童的重要。我们推测，未经治疗的儿童OSA可能会永久性地改变发育中儿童的最终认知潜力，导致终身的健康和经济影响。儿童OSA的早期识别和治疗是否可以逆转本研究中确定的神经元和性能缺陷仍有待确定。目前建议的总体假设是，与儿童阻塞性睡眠呼吸暂停相关的神经心理学表现功能障碍和大脑神经元代谢物的改变是可逆的记录治疗。本申请中概述的实验方法依赖于前瞻性干预性试验（具体目标1和2）。主要研究者将在有监督的环境中培养临床研究技能，并在有才华的导师的指导下进行结构化的课程和多学科的互动。她的目标是：1）成为一名独立的研究者; 2）发展多学科合作; 3）为我们对儿童OSA后果的了解做出重要的原创性研究。约翰霍普金斯医疗机构的综合资源，追求概述的目标，以及指导以患者为导向的研究职业发展奖将为Halbower博士提供充分发挥其作为资助独立研究者潜力的能力。

DESCRIPTION (provided by applicant): Childhood obstructive sleep apnea (OSA) has a prevalence of 2-3%, but the consequences of sleep disorders in children are vastly understudied. Cognitive decrements of vigilance, executive function, and motor coordination are associated with OSA in adults; and importantly, some of these deficits are irreversible with treatment. Brain injury demonstrated by magnetic resonance spectroscopy imaging (MRSI) has been shown in adults with OSA. It remains unclear whether the developing brain has the ability to avoid permanent damage after insults from OSA, and whether neuronal changes occur early. To answer these questions, we initiated a project with a multidisciplinary collaboration of researchers at Johns Hopkins University through the General Clinical Research Center resources. Our preliminary findings, published in the Public Library of Science Medicine, provide strong evidence that childhood OSA is associated with neuropsychological dysfunction. Furthermore, using MRSI, we demonstrated a novel finding of neuronal injury in brain areas important for learning and memory in children with OSA. We speculate that untreated childhood OSA could permanently alter the developing child's ultimate cognitive potential, resulting in a lifetime of health and economic impacts. It remains to be determined if early identification and treatment of childhood OSA can reverse the neuronal and performance deficits identified in this study. The overall hypothesis of the current proposal is that neuropsychological performance dysfunctions and neuronal metabolite alterations of the brain associated with childhood obstructive sleep apnea are reversible with documented treatment. The experimental approach outlined in this application relies on a prospective interventional trial (Specific Aims 1 and 2). The principal investigator will develop skills in clinical investigation in a supervised environment with structured coursework and multidisciplinary interactions guided by talented mentors. Her goals are to 1) become an independent investigator 2) develop multidisciplinary collaborations and 3) contribute important original research to our knowledge of the consequences of childhood OSA. The combined resources of Johns Hopkins Medical Institutions, the pursuit of the outlined aims, and the Mentored Patient-Oriented Research Career Development Award will provide Dr. Halbower the ability to reach her full potential as a funded independent investigator.