Abstract:

Objective: To investigate the sleep structure and autonomic nervous function of patients with chronic insomnia combined with obstructive sleep apnea (OSA) and analyze their correlation with neuropsychological characteristics. Methods: A total of 91 patients with chronic insomnia admitted to Tianjin Medical University General Hospital and Airpot Hospital from September 2019 to June 2021 were included. They were divided into simple chronic insomnia group (insomnia group, n=46) and chronic insomnia combined with OSA group (comorbidity group, n=45) according to whether combined with OSA. And 22 volunteers matched in sex, age and education were recruited as the control group. Sleep structure and autonomic nervous function were analyzed by PSM-100A sleep breathing monitoring. Subjective sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Insomnia Severity Index (ISI). Meanwhile, neuropsychological tests were performed. Results: 1) Sleep structure: total sleep time (TST; P=0.003, 0.002), sleep efficiency (P=0.000, 0.019), proportion of rapid eye movement (REM; P=0.000, 0.015), mean arterial oxygen saturation (SaO₂; P=0.000, 0.000), minimum SaO₂ (P=0.000, 0.019) in the comorbidity group were lower than those in control group and insomnia group; while the wake times (P=0.028, 0.033) and sleep apnea hypopnea index (AHI; P=0.000, 0.000) were higher than those in control group and insomnia group. 2) Autonomic nervous function: the low frequency coupling (LFC; P=0.000, 0.006) and LFC/high frequency coupling (HFC) ratio (P=0.000, 0.009) in comorbidity group and insomnia group were higher than those in control group, while HFC (P=0.000, 0.006) and PNN50 (P=0.000, 0.047) were lower than those in control group. 3) Neuropsychological test: the comorbidity group had a lower Mini-Mental State Examination (MMSE) score than the control group (P=0.000) and insomnia group (P=0.002), and the insomnia group had a lower MMSE score than the control group (P=0.008). In terms of memory, Auditory Verbal Learning Test (AVLT)-short delayed recall, long delayed recall and recognition score were lower in the comorbidity group than those in the control group (P=0.004, 0.000, 0.000) and insomnia group (P=0.017, 0.000, 0.000). The AVLT-immediate recall score in comorbidity group was lower than that in control group (P=0.000), and the AVLT-immediate recall, long delayed recall and recognition score in insomnia group was lower than those in control group (P=0.035, 0.005, 0.020). In terms of visuospatial ability, the correct number of Benton's Judgment of Line Orientation (JLO) was less in comorbidity group than in control group (P=0.000) and insomnia group (P=0.000), and the correct number of JLO in insomnia group was less than that in control group (P=0.017). In terms of attention, the number of correct number of Digit Span Test (DST) backward, DST downback and Symbol Digit Modalities Test (SDMT) in comorbidity group was less than that in control group (P=0.000, 0.000, 0.000) and insomnia group (P=0.000, 0.000, 0.003). The correct number of DST backward and SDMT in insomnia group was less than those in control group (P=0.003, 0.003). In terms of executive function, the correct numbers of Stroop Color-Word Test (SCWT)-A, SCWT-B and SCWT-C in the comorbidity group were less than those in the control group (P=0.000, 0.000, 0.000) and insomnia group (P=0.004, 0.025, 0.044). The correct numbers of SCWT-A, SCWT-B and SCWT-C in insomnia group were less than those in control group (P=0.003, 0.007, 0.011). In terms of anxiety and depression, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) in the comorbidity group were higher than those in control group (P=0.000, 0.000) and insomnia group (P=0.000, 0.000), and the scores of HAMA and HAMD in insomnia group were also higher than those in control group (P=0.000, 0.000). 4) The correlation of sleep structure and autonomic nervous function with neuropsychological characteristics: the TST in comorborbity group was positively correlated with the correct number of DST downback (r=0.325, P=0.031); the proportion of REM was positively correlated with AVLT-immediate recall (r=0.302, P=0.047), short delayed recall (r=0.299, P=0.049), long delayed recall (r=0.480, P=0.001) score, and the correct number of SCWT-A (r=0.311, P=0.040). AHI was negatively correlated with JLO (r=-0.432, P=0.003), the correct number of DST downback (r=-0.370, P=0.013), SDMT (r=-0.449, P=0.002), and positively correlated with HAMA (r=0.407, P=0.006) and HAMD (r=0.446, P=0.013) score. The average SaO₂ was positively correlated with the correct number of DST (r=0.397, P=0.008), and negatively correlated with HAMA (r=-0.370, P=0.013) and HAMD (r=-0.351, P=0.020) score. The minimum SaO₂ was positively correlated with the correct number of JLO (r=0.473, P=0.001). LFC was positively correlated with HAMA (r=0.428, P=0.004) and HAMD (r=0.337, P=0.025) score. HFC was negatively correlated with HAMA (r=-0.428, P=0.004) and HAMD (r=-0.337, P=0.025) score. The LFC/HFC ratio was positively correlated with HAMA (r=0.415, P=0.005) and HAMD (r=0.308, P=0.042) score. Conclusions: Patients with chronic insomnia combined with OSA have disturbed sleep structure, autonomic imbalance and cognitive decompensation, and disturbed sleep structure and autonomic nervous function may be potential mechanisms for cognitive decompensation and mood abnormalities.

Key words: Sleep initiation and maintenance disorders, Sleep apnea, obstructive, Comorbidity, Cognition disorders, Neuropsychological tests

摘要：

目的: 探讨慢性失眠合并阻塞性睡眠呼吸暂停患者睡眠结构和自主神经功能特征及其与神经心理特征的相关性。方法: 纳入2019年9月至2021年6月天津医科大学总医院和空港医院收治的91例慢性失眠患者，根据是否合并阻塞性睡眠呼吸暂停分为单纯慢性失眠组（失眠组，46例）和慢性失眠合并阻塞性睡眠呼吸暂停组（共病组，45例），同时招募性别、年龄、受教育程度相匹配的22例对照者，采用PSM-100A睡眠呼吸监测设备分析睡眠结构和自主神经功能特征，匹兹堡睡眠质量指数、Epworth嗜睡量表和失眠严重程度指数评价主观睡眠质量，并行神经心理学测验。结果: （1）睡眠结构：共病组总睡眠时间（P=0.003，0.002）、睡眠效率（P=0.000，0.019）、快速眼动睡眠期（REM）占比（P=0.000，0.015）、平均动脉血氧饱和度（SaO₂；P=0.000，0.000）、最低SaO₂（P=0.000，0.000）低于对照组和失眠组，觉醒次数（P=0.028，0.033）和睡眠呼吸暂停低通气指数（AHI；P=0.000，0.000）高于对照组和失眠组。（2）自主神经功能：共病组和失眠组低频耦合（LFC；P=0.000，0.006）和LFC/高频耦合（HFC）比值（P=0.000，0.009）高于对照组，HFC（P=0.000，0.006）和PNN50（P=0.000，0.047）低于对照组。（3）神经心理学测验：整体认知功能方面，共病组简易智能状态检查量表（MMSE）评分低于对照组（P=0.000）和失眠组（P=0.002），失眠组MMSE评分低于对照组（P=0.008）。记忆力方面，共病组听觉词语学习测验（AVLT）-短延迟回忆、长延迟回忆、再认评分低于对照组（P=0.004，0.000，0.000）和失眠组（P=0.017，0.000，0.000），共病组AVLT-即刻回忆评分低于对照组（P=0.000），失眠组AVLT-即刻回忆、长延迟回忆、再认评分低于对照组（P=0.035，0.005，0.020）。视空间能力方面，共病组本顿线方向测验（JLO）正确个数少于对照组（P=0.000）和失眠组（P=0.000），失眠组JLO正确个数少于对照组（P=0.017）。注意力方面，共病组数字广度测验（DST）顺背和倒背、符号数字转换测验（SDMT）正确个数少于对照组（P=0.000，0.000，0.000）和失眠组（P=0.000，0.000，0.003），失眠组DST倒背和SDMT正确个数少于对照组（P=0.003，0.003）。执行功能方面，共病组Stroop色词测验（SCWT）-A、SCWT-B、SCWT-C正确个数少于对照组（P=0.000，0.000，0.000）和失眠组（P=0.004，0.025，0.044），失眠组亦少于对照组（P=0.003，0.007，0.011）。焦虑和抑郁情绪方面，共病组汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）评分高于对照组（P=0.000，0.000）和失眠组（P=0.000，0.000），失眠组亦高于对照组（P=0.000，0.000）。（4）睡眠结构和自主神经功能与神经心理特征的相关性：慢性失眠合并阻塞性睡眠呼吸暂停患者总睡眠时间与DST顺背正确个数呈正相关（r=0.325，P=0.031）；REM占比与AVLT-即刻回忆（r=0.302，P=0.047）、短延迟回忆（r=0.299，P=0.049）、长延迟回忆（r=0.480，P=0.001）评分和SCWT-A正确个数（r=0.311，P=0.040）呈正相关；AHI与JLO（r=-0.432，P=0.003）、DST顺背（r=-0.370，P=0.013）、SDMT（r=-0.449，P=0.002）正确个数呈负相关，与HAMA（r=0.407，P=0.006）、HAMD（r=0.446，P=0.002）评分呈正相关；平均SaO₂与DST顺背正确个数呈正相关（r=0.397，P=0.008），与HAMA（r=-0.370，P=0.013）、HAMD（r=-0.351，P=0.020）评分呈负相关；最低SaO₂与JLO正确个数呈正相关（r=0.473，P=0.001）；LFC与HAMA（r=0.428，P=0.004）和HAMD（r=0.337，P=0.025）评分呈正相关关系；HFC与HAMA（r=-0.428，P=0.004）和HAMD（r=-0.337，P=0.025）评分呈负相关；LFC/HFC比值与HAMA（r=0.415，P=0.005）和HAMD（r=0.308，P=0.042）评分呈正相关。结论: 慢性失眠合并阻塞性睡眠呼吸暂停患者存在睡眠结构紊乱、自主神经功能障碍、认知功能障碍和情绪障碍，睡眠结构紊乱和自主神经功能障碍可能是认知功能障碍和焦虑、抑郁情绪的潜在作用机制。

关键词: 入睡和睡眠障碍, 睡眠呼吸暂停，阻塞性, 共病现象, 认知障碍, 神经心理学测验