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%，但对儿童睡眠障碍的后果研究严重不足。成人的警觉性、执行功能和运动协调能力的认知减退与阻塞性睡眠呼吸暂停有关；重要的是，其中一些缺陷在治疗后是不可逆的。磁共振波谱成像(MRSI)显示成人阻塞性睡眠呼吸暂停综合征(OSA)患者存在脑损伤。目前尚不清楚发育中的大脑是否有能力在受到阻塞性睡眠呼吸暂停综合征的侮辱后避免永久性损害，以及神经元变化是否发生在早期。为了回答这些问题，我们通过普通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。我们的初步发现发表在公共科学医学图书馆上，提供了强有力的证据，表明儿童阻塞性睡眠呼吸暂停与神经心理功能障碍有关。此外，利用磁共振成像，我们证实了阻塞性睡眠呼吸暂停综合征儿童大脑中对学习和记忆有重要影响的脑区神经元损伤的新发现。我们推测，未经治疗的儿童阻塞性睡眠呼吸暂停综合征可能会永久性地改变发育中儿童的最终认知潜力，导致终生健康和经济影响。对于儿童阻塞性睡眠呼吸暂停综合征的早期识别和治疗是否能够逆转这项研究中发现的神经元和功能缺陷仍有待确定。目前这项提议的总体假设是，与儿童阻塞性睡眠呼吸暂停相关的神经心理表现、功能障碍和脑内神经元代谢产物的改变在有记录的治疗下是可逆的。本申请中概述的实验方法依赖于前瞻性干预试验(具体目标1和2)。首席调查员将在有能力的导师的指导下，在有组织的课程作业和多学科互动的监督环境中发展临床调查技能。她的目标是1)成为一名独立的研究人员，2)发展多学科合作，3)为我们了解儿童阻塞性睡眠呼吸暂停的后果做出重要的原创性研究。约翰·霍普金斯医疗机构的资源、对概述目标的追求，以及以患者为导向的导师研究职业发展奖，将使哈尔鲍尔博士有能力充分发挥她作为一名受资助的独立研究员的潜力。

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.