睡眠纺锤波密度对阻塞性睡眠呼吸暂停低通气综合征患者记忆功能的影响

Effect of sleep spindle density on memory function in patients with 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)患者非快速动眼2(NREM2)期睡眠纺锤波密度(SSD)及其对记忆功能的影响。方法前瞻性收集苏州大学附属第二医院2021年1—12月因打鼾接受多导睡眠监测(PSG)检查的患者,最终纳入119例男性患者,年龄23~60(37.4±7.3)岁,根据呼吸暂停低通气指数(AHI)将受试者分为对照组(AHI<15次/h)59例和OSAHS组(AHI≥15次/h)60例,收集其基本信息、一般临床资料及PSG参数。记忆功能评分采用逻辑记忆测试(LMT)、数字次序测试(DOT)和CANTAB测试中的图形认知记忆(PRM)、空间识别记忆(SRM)、空间工作记忆(SWM)。人工计数NREM2期C3、C4导联睡眠纺锤波个数,计算SSD。比较上述指标及NREM2期SSD在两组之间的差异,并通过Shapiro-Wilk方法、Chi-Squared检验、Spearman相关分析、logistic回归分析探讨OSAHS患者各项记忆评分的影响因素。结果与对照组相比,OSAHS组NREM3期比例、最低血氧饱和度、NREM2期左侧中央区SSD(N2-C3 SSD)、NREM2期右侧中央区SSD(N2-C4 SSD)更低(均P<0.05);BMI、睡眠NREM1期比例、氧减指数、血氧饱和度<90%时间占总睡眠时间百分比(TS90)、呼吸暂停最长时间、呼吸相关微觉醒指数更高(均P<0.05)。与对照组相比,OSAHS组表现为LMT即刻评分更低,PRM即刻选择时间、SRM总时间、PRM延迟选择时间更长,提示OSAHS组的即刻逻辑记忆、即刻视觉记忆、空间识别记忆、延迟视觉记忆更差(均P<0.05)。多元logistic逐步回归显示:受教育年限(OR=0.744,95%CI 0.565~0.979,P=0.035)、呼吸暂停最长时间(OR=0.946,95%CI 0.898~0.997,P=0.038)、N2-C3 SSD(OR=0.328,95%CI 0.207~0.618,P=0.012)、N2-C4 SSD(OR=0.339,95%CI 0.218~0.527,P=0.017)是即刻视觉记忆的独立影响因素;AHI(OR=1.449,95%CI 1.057~1.985,P=0.021)、N2-C3 SSD(OR=0.377,95%CI 0.246~0.549,P=0.009)、N2-C4 SSD(OR=0.400,95%CI 0.267~0.600,P=0.010)是延迟视觉记忆的独立影响因素。结论SSD减低与中重度OSAHS患者记忆功能受损相关,表现在即刻视觉记忆及延迟视觉记忆受损,提示NREM2期SSD的改变可作为评估OSAHS认知功能障碍的脑电图生物标志物。

Objective To explore the characteristics of sleep spindle density in nonrapid eye movement(NREM)stage 2(N2)sleep and its effect on memory function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods Patients who underwent polysomnography(PSG)examination due to snoring in the Second Affiliated Hospital of Soochow University from January to December 2021 were prospectively collected.A total of 119 male patients,aged 23-60(37.4±7.3)years,were enrolled finally.According to the apnea hyponea index(AHI),the subjects were divided into a control group(AHI<15 times/h)of 59 cases and an OSAHS group(AHI≥15 times/h)of 60 cases.The basic information,general clinical data and PSG parameters were collected.Memory function scores were evaluated by using logical memory test(LMT),digit ordering test(DOT)and pattern recognition memory(PRM),spatial recognition memory(SRM)and spatial working memory(SWM)in CANTAB test.The number of N2 sleep spindles in leads left central area(C3)and right central area(C4)was counted by hand and the sleep spindle density(SSD)was calculated.The differences in the above indexes and N2 SSD were compared between the two groups.Shapiro-Wilk method,chi-squared test,Spearman correlation analysis and stepwise multivariate logistic regression analysis were used to investigate the influencing factors of memory scores in patients with OSAHS.Results Compared with the control group,the proportion of the slow-wave sleep,the minimum blood oxygen saturation,the SSD in C3 of NREM2 stage and the SSD in C4 of NREM2 stage were lower in the OSAHS group.The body mass index(BMI),proportion of N2 sleep,oxygen reduction index,percentage of time with oxyhemoglobin saturation below 90%(TS90),maximum duration of apnea and respiratory effort-related arousal(RERA)were higher in the OSAHS group(all P<0.05).Compared with the control group,the immediate LMT score was lower,while the time for immediately completing PRM test,the total time for immediately completing SRM test and the time for delayed completing PRM test were longer in the OSAHS group,suggesting that the immediate logical memory,immediate visual memory,spatial recognition memory and delayed visual memory were worse in the OSAHS group.Stepwise multivariate logistic regression analysis revealed that the number of years of education(OR=0.744,95%CI 0.565-0.979,P=0.035),maximum duration of apnea(OR=0.946,95%CI 0.898-0.997,P=0.038)and N2-C3 SSD(OR=0.328,95%CI 0.207-0.618,P=0.012)and N2-C4 SSD(OR=0.339,95%CI 0.218-0.527,P=0.017)were independent factors affecting the immediate visual memory.The AHI(OR=1.449,95%CI 1.057-1.985,P=0.021),N2-C3 SSD(OR=0.377,95%CI 0.246-0.549,P=0.009),and N2-C4 SSD(OR=0.400,95%CI 0.267-0.600,P=0.010)were independent factors affecting delayed visual memory.Conclusions The decrease in SSD is associated with impaired memory function in patients with moderate-severe OSAHS,which is manifested as impairment of immediate visual memory and delayed visual memory.This suggests that changes of sleep spindle wave in N2 may be an electroencephalographic biomarker for assessing cognitive impairment in OSAHS patients.