阻塞性睡眠呼吸暂停病人嗜睡的脑功能默认网络与认知功能损害机制

Excessive daytime sleepiness (EDS) and impairment of cognitive function are among the often seen symptoms in the patients with obstructive sleep apnea (OSA), but the mechanisms of central nerve system remain unclear. Default mode network (DMN) obtained by functional magnetic resonance imaging in resting state reflects regular functioning connections and intensively spontaneous activity across different brain regions under the condition that the brain without task processing in baseline state. The methods for DMN data obtaining are very similar to the protocols of multiple daytime sleepiness test (MSLT) in the requirement of the subjects’ conditions. It has been demonstrated that patients with OSA had similar abnormal brain regions to those related to inducing sleep stages 1, 2 and even 3 after sleep deprivation. Therefore, we speculate that DMN may sensitively detect the abnormal brain regions and connections which are related to EDS determined by MSLT in patients with OSA. In the current proposal, we plan to compare OSA patients between with and without EDS based on MSLT and between before and after therapy of continuous positive airway pressure (CPAP), utilizing DMN to determine the possible abnormal brain regions and connections, and their relationship to outcomes of cognitive function tasks, in order to explore the mechanisms of brain networks inducing EDS and their impact on the cognitive function. The outcomes of the research will increase our understanding to the mechanisms of EDS and impairment of cognitive function in patients with OSA and will be valuable in further development of diagnosis and treatment strategy.

嗜睡与认知功能损害是阻塞性睡眠呼吸暂停（OSA）病人常见的脑功能受损症状，但中枢机制不甚清楚。功能磁共振采集的人体在静息态下的默认模式网络（DMN）反映的是大脑处于无任务基线状态时，一些脑区存在的有规律和较强烈自发活动现象。DMN采集时对人体状态的要求与反映客观嗜睡水平的多次小睡测试（MSLT）的方法学非常类似。脑影像学技术发现OSA病人白天静息态下的异常脑区与睡眠剥夺后1和2期，甚至3期睡眠发生的脑区有较多重叠。因此推测，DMN可能敏感的探测到基于MSLT判断的OSA嗜睡相关的异常脑区和脑网络连接。本研究中，我们将采用MSLT判断的OSA嗜睡与不嗜睡病人的比较及CPAP治疗后前后的比较，用DMN探测同嗜睡可能相关的异常脑区和连接及同认知功能测量结果的关系，探讨OSA嗜睡发生的脑网络机制及对认知功能的影响。研究结果将增加我们对OSA嗜睡和认知功能损害机制的了解，为进一步的诊疗策略提供资料。

阻塞性睡眠呼吸暂停（OSA）病人常见的脑功能受损症状是嗜睡与认知功能损害，但目前其机制不清。本课题将认知功能和神经功能影像学相结合，纳入重度OSA患者，分为真性嗜睡组（MSLT<5min；ESS（Epworth嗜睡量表） 评分>10 分）、非嗜睡组（5min<MSLT<14min；ESS 评分<10 分），观察重度OSA患者在持续正压通气治疗（CPAP）前后脑微观结构和认知功能的即刻及持续性改变，探讨OSA嗜睡发生的脑网络机制及对认知功能的影响。本研究发现：1）在我国OSA患者筛查工具中，ESS准确性最小Berlin问卷可能有更高的准确性。随着BMI界值降低，Berlin问卷敏感度及阴性预测值逐步提高，但特异度及阳性预测值降低，Berlin量表的准确性可能与BMI有关。调整BMI和年龄后，不能提高STOP-Bang问卷的准确性。2）中重度OSA患者中，CPAP治疗能即刻纠正OSA患者AHI指数及夜间低氧及睡眠结构。3）与客观无嗜睡患者比较，客观嗜睡的OSA患者AHI严重程度更高，失眠严重指数量表（ISI）分值低。客观嗜睡与AHI、主观觉醒次数、睡眠效率、ESS评分负相关，与客观SL、ISI评分正相关。主观睡眠质量较差的OSA患者深睡眠减少，睡眠效率较低，客观日间嗜睡程度低，共病冠心病风险高。