Cha Jiook, Zea-Hernandez Johanna A, Sin Sanghun, Graw-Panzer Katharina, Shifteh Keivan, Isasi Carmen R, Wagshul Mark E, Moran Eileen E, Posner Jonathan, Zimmerman Molly E, Arens Raanan
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, New York 10032, and.
Division of Respiratory and Sleep Medicine, Children's Hospital at Montefiore.
J Neurosci. 2017 Apr 19;37(16):4280-4288. doi: 10.1523/JNEUROSCI.3583-16.2017. Epub 2017 Mar 20.
Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS ( = 11) and control subjects ( = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus ( = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's = -0.50, = 0.008) and a greater arousal index ( = -0.44, = 0.017). OSAS did not significantly affect neuropsychological measures ( values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity ( = 0.54, = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS. In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.
阻塞性睡眠呼吸暂停综合征（OSAS）与间歇性缺氧和睡眠不足有关。在儿童中，认知功能受损是重要表现，但潜在病理机制尚不清楚。我们推测OSAS会影响齿状回，这是海马体的一个亚区，对神经发生和认知至关重要，并且这种影响会进一步影响儿童的认知功能。在患有OSAS的儿童（n = 11）和对照组（n = 12；年龄和性别匹配）中，我们进行了扩散张量成像和结构MRI、多导睡眠图以及神经心理学评估。我们发现OSAS与左侧齿状回平均扩散率降低有关（P = 0.002；校正错误发现率；校正性别、年龄和体重指数后），显示出较大的效应量（偏η² = 0.491），但与大脑其他任何结构测量指标均无关。齿状回平均扩散率降低与较高的呼吸暂停低通气指数（斯皮尔曼相关性系数r = -0.50，P = 0.008）和较高的觉醒指数（r = -0.44，P = 0.017）相关。OSAS对神经心理学测量指标没有显著影响（P值>0.5）；然而，较低的言语学习分数与较低的齿状回平均扩散率相关（r = 0.54，P = 0.004）。路径分析表明，齿状回平均扩散率介导了OSAS对言语学习能力的影响。最后，基于齿状回平均扩散率的回归模型的诊断准确率达到85.8%（交叉验证）。本研究证明了OSAS对儿童神经认知功能影响的可能途径，以及齿状回平均扩散率作为OSAS儿童脑病理早期标志物的潜在效用。在本研究中，我们调查了齿状回结构、海马体依赖的认知与阻塞性睡眠呼吸暂停综合征（OSAS）之间的关系。我们证明了患有OSAS的儿童齿状回平均扩散率较低，这与较低的言语学习和记忆分数相关。本研究为患有OSAS的儿童齿状回微观结构破坏提供了新证据，这可能有助于解释这些儿童中描述的一些神经认知缺陷。
