OSAHS 患者血清炎症指标和认知功能的相关性及持续气道正压通气的疗效

Association between inflammation and cognitive function and effects of continuous positive airway pressure treatment in obstructive sleep apnea hypopnea syndrome

目的：探讨阻塞性睡眠呼吸暂停低通气综合征（ OSAHS）患者血清炎症指标和认知功能的相关性及持续气道正压通气（ CPAP）的疗效。方法纳入自2011年6月至2013年4月在苏州大学附属第二医院睡眠中心行多导睡眠图（ PSG）监测并符合本研究入组标准的患者139例，根据呼吸暂停低通气指数（ AHI）分为单纯鼾症组18例，轻度OSAHS组23例，中度OSAHS组29例，重度OSAHS组69例。利用蒙特利尔认知评估量表（MoCA）、简易精神状态检查量表（MMSE），Epworth嗜睡量表（ESS）评估认知功能及日间嗜睡程度，检测血清中超敏C反应蛋白（Hs－CRP）、肿瘤坏死因子－α（ TNF－α）、瘦素的水平，分析各组患者认知功能评分、血清炎症指标及PSG参数之间的差异及相关性。分析33例接受长期家庭CPAP治疗的重度OSAHS患者（治疗组）治疗前后有关指标的变化。结果重度 OSAHS 组血清 Hs－CRP、TNF－α、瘦素水平分别为（1．77±1．19） mg／L、（21．04±7．78）pmol／L、（15．21±13．26）mmol／L，均显著高于单纯鼾症组的（0．92±0．82）mg／L、（10．30±5．23） pmol／L、（6．35±4．51） mmol／L（ P＜0．05）；校正了年龄、体质指数（ BMI）和受教育年限后，MoCA评分与血清TNF－α水平、AHI、氧减指数（ ODI ）、血氧饱和度＜90％的时间比率（ TS90％）呈负相关（r＝－0．266、－0．236、－0．201、－0．180），与血氧饱和度夜间最低值（LSaO2）呈正相关（r＝0．224）（均P＜0．05），认知功能损伤主要表现在视空间与执行力、注意及延迟回忆。治疗组治疗时间＞6个月，依从性良好，治疗后患者血清中Hs－CRP、TNF－α和瘦素水平分别为（1．20±0．88）mg／L，（14．12±4．34）pmol／L及（7．37±5．30） mmol／L，较治疗前的（2．03±1．58） mg／L，（22．74±6．72） pmol／L 及（13．69±7．17）mmol／L均显著降低，MoCA评分（27．79±1．69）及ESS评分（4．33±3．14）较治疗前（24．76±2．57）及（12．61±5．80）改善（均P＜0．01），MoCA量表各子项评分均较治疗前有所改善。结论 OSAHS患者存在认知功能障碍及炎症反应增高，认知功能与血清TNF－α水平及夜间间歇低氧相关，提示炎症反应参与间歇低氧诱导的认知功能障碍的发生；长期CPAP治疗可减轻OSAHS患者血清炎症反应，并改善认知功能损伤。

Objective To explore the association between serum inflammation levels and cognitive function in patients with obstructive sleep apnea-hypopnea syndromes （ OSAHS） and evaluate the effects of continuous positive airway pressure treatment （ CPAP） on serum inflammation levels and cognitive function . Methods A total of 139 eligible patients were monitored by overnight polysomnography （ PSG） at Sleep Center, Second Affiliated Hospital , Soochow University from June 2011 to April 2013.Based on the results of apnea-hypopnea index （AHI）, they were divided into 4 groups of primary snoring （n=18）, mild OSAHS （ n =23 ） , moderate OSAHS （ n =29 ） and severe OSAHS （ n =69 ） .The questionnaires of Montreal Cognitive Assessment （ MoCA ） , Mini-Mental State Examination （ MMSE ） and Epworth Sleepiness Scale （ ESS ） were administered to assess cognitive function and daytime sleepiness .The serum levels of high-sensitivity C-reactive protein （ Hs-CRP） , leptin and tumor necrosis factor alpha （ TNF-α） were detected to evaluate systemic inflammation.The questionnaire scores , serum levels of Hs-CRP, leptin and TNF-αand PSG parameters were compared among 4 groups.Thirty-three patients in severe OSAHS group （ treatment group） with good adherence were evaluated at baseline and after long-time CPAP treatment. Results Compared to primary snoring group, the serum Hs-CRP （（1.77 ±1.19） vs （0.92 ±0.82） mg/L）, leptin （（15.21 ±13.26） vs （6.35 ±4.51） mmol/L） and TNF-α（（21.04 ±7.78） vs （10.30 ±5.23） pmol/L） levels increased significantly in severe OSAHS group （ P 〈0.05 ） .After adjusting for body mass index （ BMI ） , age and education years , MoCA scores showed negative correlations with serum TNF-α, AHI, oxygen reduction index （ ODI） and TS90% （ r=-0.266, -0.236, -0.201, -0.18 respectively, all P〈0.05） and positive correlations with minimum oxygen saturation （LSaO2）（r=0.224, P〈0.05）.The evaluations of MoCA subdomains further revealed selective reductions in visual space , executive function , attention and delayed memory function .The treatment group with good adherence to 〉6-month continuous positive airway pressure （ CPAP） treatment and after CPAP treatment , the serum levels of Hs-CRP, TNF-αand leptin improved markedly （ （ 1.20 ±0.88 ） vs （ 2.03 ±1.58 ） mg/L, （ 14.12 ±4.34 ） vs （ 22.74 ± 6.72） pmol/L and （7.37 ±5.30） vs （13.69 ±7.17） mmol/L respectively）.The scores of MoCA and ESS also improved （27.79 ±1.69 vs 24.76 ±2.57, 4.33 ±3.14 vs 12.61 ±5.80 respectively） （all P〈0.01）. The score of all MoCA subdomains improved after treatment .Conclusions Cognitive dysfunction and inflammatory reaction are common in OSAHS patients .MoCA scores are correlated significantly with serum level of TNF-αand nocturnal intermittent hypoxia .Systemic inflammation may play an important role in cognitive dysfunction of OSAHS patients .And long-time CPAP treatment can improve systemic inflammatory response and cognitive impairment .