Differences in arousal response between aged and middle-aged patients with obstructive sleep apnea syndrome

Abstract The aim of this study is to show the clinical significance of the differences in arousal response at a termination of apnea/hypopnea between aged and middle-aged patients with obstructive sleep apnea syndrome (OSAS). We polygraphically assessed electrocardiographic (ECG) and electroencephalographic (EEG) arousal. Electrocardiographic arousal was defined as an abrupt increase in heart rate at a termination of apnea/hypopnea. Our findings showed that EEG and ECG arousal at a termination of apnea/hypopnea were significantly suppressed in aged patients with OSAS, which might provide useful information on the pathophysiology of OSAS.     

伴中重度阻塞性睡眠呼吸暂停低通气综合征的抑郁症患者多导睡眠监测特点

目的 探讨伴中重度阻塞性睡眠呼吸暂停低通气综合征（OSAHS）的抑郁症患者多导睡眠监测（PSG）特点。方法 回顾性分析2017年12月-2019年10月在苏州市广济医院睡眠医学中心完成整夜多导睡眠监测（PSG）的门诊和住院患者以及健康体检人群,从中筛选出四组被试,分别为伴中重度OSAHS的抑郁症患者（n=31）、不伴OSAHS的抑郁症患者（n=79）、中重度OSAHS患者（n=96）和正常对照组（n=32）。比较四组被试睡眠进程相关指标（总睡眠时间、睡眠潜伏期、觉醒次数）和睡眠结构相关指标（N1、N2、N3期及REM期占总睡眠时间的比例,REM潜伏期、REM期持续时间）以及睡眠呼吸相关指标（氧减指数）等参数。结果 睡眠进程方面,四组被试总睡眠时间、睡眠潜伏期和觉醒次数差异均有统计学意义（F=2.874、3.959、12.291,P<0.05或0.01）。睡眠结构方面,四组被试N2期、N3期占总睡眠时间比例差异均有统计学意义（F=13.885、48.013,P均<0.01）;四组被试REM潜伏期、REM期持续时间、REM期占总睡眠时间比例差异均有统计学意义（F=41.492、11.827、10.552,P均<0.01）。睡眠呼吸相关指标方面,四组被试氧减指数差异有统计学意义（F=170.585,P<0.05）。结论 伴中重度OSAHS的抑郁症患者存在严重的睡眠进程和结构紊乱,同时伴有更频繁和更严重的呼吸相关事件。     

Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome

Excessive daytime sleepiness (EDS) is the major symptom of patients with obstructive sleep apnea syndrome (OSAS). In this study, we examined the relationship between subjective EDS scored with the Epworth Sleepiness Scale (ESS), objective EDS measured with the multiple sleep latency test (MSLT) and sleep variables evaluated with polysomnography for patients with OSAS. Subjects were 10 patients (51.7+/-19.0 years old). The average ESS and MSLT scores were 10.6+/-5.6 and 7.7+/-5.6, respectively. There was no significant relationship between ESS and MSLT. The Multiple Sleep Latency Test had a significant negative relationship with the number of awakenings and the apnea/hypopnea index. No relationship was found between nocturnal hypoxia and either ESS or MSLT. Our findings suggest that objective EDS in OSAS is related with fragmentation of sleep, and that several patients are not aware of their EDS.     

Neuropsychological correlates of obstructive sleep apnea severity in patients with epilepsy

Aims. Obstructive sleep apnea affects up to 30% of patients with epilepsy. As obstructive sleep apnea represents a clinical risk factor for cognitive deficits, its occurrence in epilepsy patients may exacerbate cognitive deficits associated with this condition. However, the cognitive burden of obstructive sleep apnea in epilepsy remains poorly understood. We conducted a retrospective record review of adults with epilepsy who underwent a polysomnography and a neuropsychological assessment at Brigham and Women's Hospital. Methods. We examined the relationship between obstructive sleep apnea severity and cognitive functioning, particularly attention/executive functions, memory, and processing speed in untreated obstructive sleep apnea patients with epilepsy. Twenty patients with epilepsy and mild‐to‐severe obstructive sleep apnea were included in the analyses. Results. We found significant positive correlations between the oxygen saturation levels during rapid‐eye‐movement sleep and attention/executive tests (p<0.05), as well as time spent with saturation levels ≤90% and executive functioning (p=0.008). Similarly, worse verbal memory performances were associated with lower oxygen levels (p=0.003). In addition, more severe respiratory events during rapid‐eye‐movement sleep were associated with worse performances on attention tests (p=0.03). Conclusions. Our findings indicate that more severe obstructive sleep apnea‐related hypoxemia during sleep is associated with poorer cognitive performances on tests that assess attention/executive functions and verbal memory in patients with epilepsy. Overall, these results are consistent with the sleep apnea literature, and suggest that patients with epilepsy are also vulnerable to the effects of obstructive sleep apnea. Future prospective studies will help in determining whether treatment of obstructive sleep apnea may help improve cognitive functioning in patients with epilepsy.     

Increased cell‐free DNA concentrations in patients with obstructive sleep apnea

Aim: Blood concentrations of cell‐free DNA, which is considered to be released during apoptosis, are elevated under some pathological conditions such as cardiovascular disease and cancer. The association between obstructive sleep apnea (OSA) and cell‐free DNA concentrations has not been reported so far. The purpose of the present study was to examine the association between OSA and plasma DNA concentrations. Methods: A case–control study was conducted using a total of 164 men aged 39–67 years, who were free of coronary heart disease and cancer. Laboratory‐based overnight polysomnography was performed for all participants. Results: On the basis of polysomnography, patients with an apnea–hypopnea index (AHI) = 5–30 events/h were defined as having mild–moderate OSA (n = 33) and those with >30 events/h were defined as having severe OSA (n = 49). All 82 controls had AHI < 5 events/h. Plasma DNA concentrations from all participants were analyzed for the β‐globin gene using fluorescence‐based real‐time polymerase chain reaction. Patients with severe OSA had significantly higher plasma DNA concentrations than persons with mild–moderate OSA and those without OSA (P < 0.05). AHI was significantly associated with body mass index (P < 0.001), hypertension (P < 0.001), and plasma DNA concentration (P < 0.05). Conclusion: After taking into account hypertension and other potential risk factors, persons with high plasma DNA concentrations (>8 µg/L) had approximately fourfold higher odds of OSA than those with low DNA levels. Further data are warranted to confirm the association for men and to evaluate the association for women.     

Facial patterns of obstructive sleep apnea patients using Ricketts' method

To analyze the facial patterns of obstructive sleep apnea syndrome (OSAS) patients, we took lateral cephalograms of 31 OSAS patients and 26 non-OSAS controls and utilized Ricketts' method. In addition, we measured the hyoid bone position, the length of mandibular plane to H-point, the length of soft palate, and lower pharynx. The facial patterns of OSAS patients were dolico, the hyoid bone was positioned low, the soft palate was longer and the width of the airway was narrower than that of the non-OSAS controls.     

Daytime sleepiness and automobile accidents in patients with obstructive sleep apnea syndrome

Abstract We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near-miss accident. Automobile accidents and near-misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score ( r = 0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.     

Detection of cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome using mismatch negativity

In this experiment,97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups(mild,moderate,severe) according to minimum oxygen saturation,and 35 healthy subjects were examined as controls.Cognitive function was determined using the mismatch negativity paradigm and the Montreal Cognitive Assessment.The results revealed that as the disease worsened,the mismatch negativity latency was gradually extended,and the amplitude gradually declined in patients with obstructive sleep apnea hypopnea syndrome.Importantly,mismatch negativity latency in severe patients with a persistent time of minimum oxygen saturation < 60 seconds was significantly shorter than that with a persistent time of minimum oxygen saturation > 60 seconds.Correlation analysis revealed a negative correlation between minimum oxygen saturation latency and Montreal Cognitive Assessment scores.These findings indicate that intermittent night-time hypoxemia affects mismatch negativity waveforms and Montreal Cognitive Assessment scores.As indicators for detecting the cognitive functional status of obstructive sleep apnea hypopnea syndrome patients,the sensitivity of mismatch negativity is 82.93%,the specificity is 73.33%,the accuracy rate is 81.52%,the positive predictive value is 85.00%,the negative predictive value is 70.21%,the positive likelihood ratio is 3,and the negative likelihood ratio is 0.23.These results indicate that mismatch negativity can be used as an effective tool for diagnosis of cognitive dysfunction in obstructive sleep apnea hypopnea syndrome patients.     

Polysomnographic and urodynamic changes in a case of obstructive sleep apnea syndrome with enuresis

A 53-year-old female patient with obstructive sleep apnea syndrome was reported. She had complained of enuresis as well as a 15-year history of snoring, but she had no complaint of sleep and awake disturbance. Polysomnographic study showed repeated obstructive apnea and hypopnea with an apnea/hypopnea index of 52.6, and severe oxygen desaturation during sleep. On cystometography during sleep, the changing amplitude of the spike wave corresponds to the changes of respiratory efforts against a closed upper airway. The patient was treated successfully with imipramine and acetazolamide for the obstructive sleep apnea and enuresis. Apnea/hypopnea index, nocturnal oxygen desaturation, and sleep architecture were improved, and enuresis completely disappeared. Cystometrography during sleep showed that the average amplitude of the spike wave tended to be low. Percentage urinary volume during sleep compared with 24 h volume was significantly reduced. We considered that the enuresis was mainly related to increased intra-abdominal pressure produced by respiratory efforts and enhanced nocturnal urine production.     

Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome

Abstract The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40–64 years), and aged (65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17–78 years (136 men, 12 women, mean 52.0±12.3 yean), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval:55.6–87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19–year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO₂) fell below 90% (time of SaO₂ < 90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO₂ <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO₂, and time of SaO₂ <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.     

Cerebrovascular reactivity and neurovascular coupling in patients with obstructive sleep apnea

Aim: Obstructive sleep apnea syndrome (OSAS) has been implicated as an independent risk factor for stroke. There are data suggesting the presence of lower cerebrovascular reactivity (CVR) as determined by transcranial Doppler (TCD) in patients with OSAS. We concurrently investigated neurovascular coupling (NVC) with visual stimulation, and CVR using breath-holding (BH) test on TCD in patients with OSAS. Materials and methods: Data were collected in 49 patients with moderate to severe OSAS, and compared to 15 healthy subjects matched for age and risk factors. The CVR to hypercapnia was measured by BH test, and the NVC was performed with visual stimulation. Results: There were no significant differences in baseline characteristics of patients and controls, except for BMI, which was significantly higher in patients with OSAS (p = 0.036). OSAS patients showed significantly lower reactivity during BH in comparison to controls (36.9% ± 14.0% vs. 46.6% ± 20.1%; p = 0.019). The reactivity time was also significantly shorter in the OSAS group (8.0 ± 4.2 s) when compared to controls (10.1 ± 4.3 s; p = 0.015). The visual stimulation produced similar reactivity in patients (27.7% ± 9.4%) and controls (29.1 ± 13.9; p > 0.05). Conclusions: Our data demonstrate a diminished vasodilator response capacity only to a strong stimulator such as hypercapnia in OSAS patients. However, the NVC, as shown by the TCD, is quite normal, suggesting that a weak or mild stimulation produces a proper reactivity among OSAS patients.     

A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea

Background and purpose: Repeated episodes of hypoxia, hypercapnia and transient blood pressure elevation in obstructive sleep apnea syndrome (OSAS) may damage neutral structures and induce cerebral metabolic impairment. This study aimed to determine the impact of OSAS on cerebral metabolites measured by ¹H magnetic resonance spectroscopy (¹H ‐MRS). Methods: Twenty OSAS patients underwent standard overnight polysomnography and ¹H‐MRS separately. Proton volumes of interest (VOIs) were placed in frontal and midtemporal regions bilaterally. Results: Significantly lower values of the N‐acetylaspartate (NAA)/creatine (Cr) ratio were found in frontal regions (P < 0.004) compared with 20 age‐matched control subjects. A significant increase in the myo‐inositol (Ins)/Cr ratio was evident bilaterally in temporal and frontal regions (P < 0.00002 and P < 0.04). Choline (Cho)/Cr ratio values were also significantly greater in temporal regions (P < 0.00001). A significant negative correlation (r = ?0.51, P < 0.03) was found between the apnea‐hypopnea index (AHI) and NAA/Cr ratio in the frontal regions of OSAS patients. Conclusions: Reduction in the NAA/Cr ratio in frontal regions of OSAS patients could be related to neural loss. Increase in the Cho/Cr ratio in temporal regions and Ins/Cr ratio in both frontal and temporal regions could be interpreted as evidence of membrane breakdown and reactive gliosis, respectively, consequent to repeated episodes of hypoxia in OSAS.     

Headache characteristics in obstructive sleep apnea syndrome and insomnia

OBJECTIVES: To determine headache characteristics in the obstructive sleep apnea syndrome (OSAS) and in insomnia. PATIENTS AND METHODS: Fifty-six OSAS patients and 50 insomnia patients were assessed in the same time period. Patients in both groups underwent an accurate interview to investigate headache occurrence and its characteristics. Results - Headache was reported by 49% of OSAS patients and 48% of insomnia patients. In OSAS patients headache had most frequently a tension-type pattern. Headache occurred on awakening in 74% of OSAS patients, more frequently than in insomnia patients (40%) (chi(2); P < 0.04). The occurrence of morning headache appears to be significantly correlated with nocturnal oxygen desaturation and OSAS severity. CONCLUSION: Headache is a common finding in both OSAS and insomnia patients. Because morning headache seems to be more specific for OSAS than insomnia, and in OSAS its occurrence seems to be associated with disease severity, we hypothesize the involvement of certain pathogenic mechanisms associated with OSAS.     

Factors influencing subjective sleepiness in patients with obstructive sleep apnea syndrome

The aim of the present paper was to clarify the factors influencing subjective daytime sleepiness in patients with obstructive sleep apnea syndrome (OSAS). Subjects included 230 adult male OSAS patients aged 20-73 years. Single and multiple linear regression analyses were performed to estimate the association between the Epworth Sleepiness Scale (ESS) and the following variables: Minnesota Multiphasic Personality Inventory (MMPI), Self-Rating Depression Scale (SDS), age, body mass index (BMI), sleep duration during the preceding month and apnea-hypopnea index (AHI). Single linear regression analysis showed that age had a negative association with ESS score, while BMI, AHI, SDS, hypochondriasis (Hs), hysteria, psychopathic deviant, psychasthenia, schizophrenia and hypomania on the MMPI had a positive association with ESS score. However, the other remaining parameters such as nocturnal sleep duration during the preceding month, depression, masculinity-femininity, paranoia, social introversion on the MMPI had no statistical association with ESS score. Multiple linear regression analysis with stepwise elimination method was applied to choose the significant factors associated with ESS. It was found that three variables including age, AHI and Hs scores were independent factors influencing ESS score. The R(2) for the model was 0.14, suggesting that these factors account for 14% of possible variance of subjective daytime sleepiness of OSAS patients. These results suggest that subjective daytime sleepiness in patients with OSAS may be influenced not only by the severity of respiratory disorder indices but also by certain personality characteristics affecting Hs score and by age.     

A review of executive functions in obstructive sleep apnea syndrome

OBJECTIVES: To provide an update on recent research concerning obstructive sleep apnea syndrome (OSAS) and executive functions. METHODS: A systematic review was carried out on reports drawn from MEDLINE and PSYCHLIT (January 1990-December 2005) and identified from lists of references in these reports. The selection criteria were met by 40 articles. RESULTS: The sample sizes in the reviewed studies varied widely and consisted mostly of selected groups. Most patient samples were heterogeneous in terms of the severity of OSAS. Executive functions were generally assessed with standardized test methods. Half of the studies assessed executive functions using only one or two tests. The most defected domains of executive functions were working memory, phonological fluency, cognitive flexibility, and planning. Continuous positive airway pressure (CPAP) treatment improved performance times, cognitive flexibility, and planning. Deficits in working memory and phonological fluency persisted. CONCLUSIONS: Executive functions are the most defected cognitive domain in OSAS. Previous studies are affected by the heterogeneity of patient samples and the definitions of the domains of executive functions. Executive functions in OSAS should be assessed with a standardized neuropsychological test battery including assessments of different domains of executive functions. More research is needed on the efficiency of CPAP treatment on executive dysfunctions.     

Obstructive sleep apnea and neurocognitive performance: the role of cortisol

BackgroundObstructive sleep apnea (OSA) is a prevalent disorder with multiple consequences including negative effects on neurocognitive function. Several domains of cognitive function are impaired in OSA patients, but the mechanisms through which this sleep disorder results in impairment are not clear. Given the well-known effects of cortisol on cognitive function, in particular memory, the dysregulating effects of OSA on cortisol levels are hypothesized as a potential pathway leading to cognitive impairment.MethodsFifty-five participants with OSA (mean apnea-hypopnea index [AHI], 30.3) were assessed over 2 days. Over a 24-h period, blood samples were collected every 2 h to examine cortisol levels. The following night, sleep was monitored with polysomnography (PSG). Participants were given a battery of neurocognitive tests, which assessed seven cognitive domains.ResultsOSA severity assessed by oxygen desaturation index (ODI) was associated with 24-h cortisol levels. AHI, ODI, and nighttime cortisol levels were associated with global deficit scores (GDS) in cognitive functioning, particularly in domains of learning, memory, and working memory (P < .05 for all). Hierarchical linear regression analysis revealed that nighttime cortisol accounted for 9–16% of variance in learning (P = .018), memory (P = .003), and working memory (P = .016) domains, though apnea severity did not significantly predict any additional variance.ConclusionsIn our sample of patients with OSA, nocturnal cortisol levels were associated with neuropsychologic functioning above and beyond the influence of covariates and apnea severity. These findings suggest that OSA-related alterations in cortisol activity may partially explain the pathophysiology of neuropsychologic impairments in sleep apnea.     

Autonomic cardiovascular control in children with obstructive sleep apnea

Autonomic cardiorespiratory control changes with sleep-wake states and is influenced by sleep-related breathing disorders. Power spectrum (PS) analysis of instantaneous fluctuations in heart rate (HR) is used to investigate the role of the autonomic nervous system (ANS) in cardiorespiratory control. The two spectral regions of interest are the low frequency component (LF) and high frequency component (HF). The aim of the present study was to investigate the autonomic cardiorespiratory control in children with obstructive sleep apnea (OSA) syndrome. We studied 10 children with OSA versus 10 normal children. All subjects underwent whole night polysomnography. Spectral analysis of the HR and breathing signals was performed for 256 second long, artifact-free epochs in each sleep-wake state. The LF power was higher in the OSA group compared with control subjects for all states, reflecting enhanced sympathetic activity in OSA subjects. The results indicated sympathetic predominance during REM sleep in all subjects and parasympathetic predominance in slow wave sleep only in controls. The autonomic balance (LF/HF) was significantly higher in OSA patients than in control subjects, at all stages during night sleep, and while awake before sleep onset. An index of overall autonomic balance (ABI) was computed for each subject and correlated well with the measured respiratory disturbance index (RDI).     

Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated with intermittent hypoxia and cognitive decrements. As the hippocampus is particularly susceptible to hypoxia, we hypothesized that it may show biochemical abnormalities, and they may relate to apnea severity. PATIENTS AND METHODS: Eight males with OSA and five age-matched controls underwent neurocognitive testing before and after polysomnography and proton magnetic resonance spectra were obtained from the left hippocampal area of all subjects. RESULTS: In the left hippocampal area, N-acetyl-containing/creatine-containing compounds was significantly increased in OSA (P=0.04). Inspection of these compounds with respect to the water resonance indicated that this was most likely due to a decrease in creatine-containing compounds rather than any change in N-acetyl-containing compounds. Lower levels of hippocampal creatine-containing compounds were correlated with worse OSA severity and neurocognitive performance. CONCLUSIONS: We suggest the changes in creatine levels in the hippocampal area represent adjustments to brain bioenergetics, similar to those seen in ischemic preconditioning, and may reflect the different susceptibility of these tissues to hypoxic damage in OSA.