Gender Difference in REM Sleep Behavior Disorder in Japanese Population: Polysomnography and Sleep Questionnaire Study.

Rapid eye movement (REM) sleep behavior disorder (RBD) is generally common among males and is an established risk factor for neurodegenerative diseases. As the population ages, the prevalence of α-synucleinopathy (such as Parkinson's disease) is increasing. Additionally, the number of female patients is increasing in Japan. Therefore, we aimed to clarify the clinical characteristics of RBD from the perspective of gender differences in the Japanese population. The proportion of male RBD patients (65.2%) was significantly higher than that of female patients (34.8%). Additionally, female patients (70.5 ± 8.2 years) were significantly older than male patients (67.9 ± 8.0 years, p < 0.05). The mean score on the RBD Screening Questionnaire was significantly higher in male patients than in female (8.6 ± 2.9 vs. 7.7 ± 3.1, p < 0.05), while the mean score on the Pittsburgh Sleep Quality Index was significantly higher in males (5.9 ± 3.8 vs. 7.2 ± 3.600, p < 0.001). The Self-rating Depression Scale in females was 41.7 ± 8.5, and they were more likely to show depressive tendencies than males. In polysomnography, higher rates of obstructive sleep apnea and longer duration of stage N1 sleep were detected in males. After adjusting for age, BMI, and polysomnographic parameters, we found that female RBD patients had significantly worse sleep quality and rates of depression compared to male patients.

Association between Rapid Eye Movement Obstructive Sleep Apnea and Metabolic Syndrome in a Japanese Population.

Objective Rapid eye movement (REM) obstructive sleep apnea (OSA) is characterized by apnea and hypopnea events due to airway collapse occurring predominantly or exclusively during REM sleep. OSA is a potential risk factor for metabolic dysfunction. However, the association between REM OSA and risk of adverse health outcomes remains unclear. The present study investigated the association between REM OSA and metabolic syndrome (MetS), including the MetS components of hypertension, dyslipidemia, and hyperglycemia, in the Japanese population. Methods In total, 836 Japanese patients with mild to moderate OSA were enrolled in this study. We compared the prevalence of MetS, including hypertension, dyslipidemia, and hyperglycemia, between REM OSA and non-REM OSA via univariate analyses of descriptive statistics and logistic regression analyses. Results The prevalence of hypertension was 68.3% in the REM OSA group and 56.6% in the non-REM OSA group (p<0.05). In addition, the prevalence of metabolic syndrome was significantly higher (37.0%) in the REM OSA group than in the non-REM-OSA group (25.2%). Logistic regression analyses showed that the prevalence of hypertension and MetS was significantly greater in the REM OSA group than in the non-REM-OSA group. Conclusion Our findings suggest that patients with REM OSA, regardless of age, sex, and body mass index, are at a higher risk of developing hypertension and MetS than patients with non-REM OSA.

Advanced emergency braking system reduces the risk of motor vehicle collisions caused by falling asleep while driving in patients with untreated obstructive sleep apnea.

Obstructive sleep apnea leads to excessive daytime sleepiness and cognitive dysfunction, which are risk factors for motor vehicle collisions. We aimed to clarify if vehicles with an advanced emergency braking system could reduce motor vehicle collisions caused by falling asleep while driving among patients with untreated obstructive sleep apnea. We enrolled patients with untreated obstructive sleep apnea who underwent polysomnography. The questionnaires included the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, history of drowsy driving accidents, and use of an advanced emergency braking system. Multivariate analysis was performed, and odds ratios and 95% confidence intervals were calculated. This study included 1097 patients (mean age, 51.2 ± 12.9 years). Collisions caused by falling asleep while driving were recorded in 59 (5.4%) patients, and were more frequently observed in vehicles without an advanced emergency braking system (p = 0.045). Multivariate analysis showed that these collisions were associated with use of an advanced emergency braking system (odds ratio [95% confidence interval]: 0.39 [0.16-0.97], p = 0.04), length of driving (2.79 [1.19-6.50], p = 0.02), total sleep time (2.40 [1.62-3.55], p < 0.0001), sleep efficiency (0.94 [0.90-0.98], p = 0.003) and periodic limb movement index (1.02 [1.01-1.03], p = 0.004). The collision risk caused by falling asleep while driving in vehicles with an advanced emergency braking system was significantly lower. This study indicates that advanced emergency braking systems may be a preventive measure to reduce motor vehicle collisions among patients with untreated obstructive sleep apnea.

Efficacy of a Combination Therapy for Difficulties Waking Up in Non-School-Attending Students.

School non-attendance due to difficulties waking up is increasing in Japan, and affected students are commonly diagnosed with orthostatic dysregulation (OD); however, OD-associated sleep problems are overlooked. To date, no sleep-medicine-based treatment for wake-up difficulties in non-school-attending students has been established. This study aimed to assess the efficacy of a novel combination therapy for these students. We assessed the combined effect of sleep hygiene guidance, low-dose aripiprazole administration (3 mg/day), and blue-light exposure on wake-up difficulty in 21 non-school-attending teenage patients. The patients were evaluated using sleep studies and questionnaires before and after treatment. The average subjective total sleep time calculated from sleep diaries before treatment in the patients was 10.3 h. The therapy improved wake-up difficulty by 85.7% and further improved school non-attendance by 66.7%. The subjective sleep time significantly decreased by 9.5 h after treatment (p = 0.0004). The self-rating Depression Scale and mental component summary of the 36-item Short-Form Health Survey significantly improved after treatment (p = 0.002 and p = 0.01, respectively). Wake-up difficulties were caused by the addition of a delayed sleep phase to the patients' long sleep times. The novel combination therapy was effective in improving wake-up difficulty and mental quality of life in non-school-attending teenage students.

Estimated respiratory arousal threshold in patients with rapid eye movement obstructive sleep apnea.

PURPOSE: Rapid eye movement (REM) obstructive sleep apnea (OSA) is a prevalent clinical phenotype. However, the literature focusing on the pathophysiology of REM OSA is limited. This study compared the proportion of individuals with a low respiratory arousal threshold between patients with REM and non-REM OSA. METHODS: REM OSA was defined as having an apnea-hypopnea index (AHI) ≥ 5 and AHI during REM (AHI-REM)/AHI during NREM (AHI-NREM) ≥ 2. REM OSA was sub-divided into REM-predominant OSA and REM-isolated OSA. REM-predominant OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM ≥ 5. REM-isolated OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM < 5. Patients with an AHI-REM/AHI-NREM < 2 were defined as having non-REM OSA. A low respiratory arousal threshold was defined as having 2 or more of the following conditions: AHI < 30 events/h, proportion of hypopnea > 58.3%, and nadir SpO2 > 82.5%. RESULTS: The proportions of individuals with low respiratory arousal thresholds among individuals with REM-predominant OSA and REM-isolated OSA were significantly higher (77.2% and 93.7%, respectively) than that of patients with non-REM OSA (48.6%). This was also true when the analysis was performed according to sex. CONCLUSION: These results indicate that a low respiratory arousal threshold might be an important endotype that contributes to the pathogenesis of REM OSA, especially in REM-isolated OSA.

Nocturnal Blood Pressure Fluctuations in Patients with Rapid Eye Movement-Related Obstructive Sleep Apnea.

Rapid eye movement-related obstructive sleep apnea (REM-related OSA) is a polysomnographic phenotype. Nocturnal blood pressure (BP) fluctuations remain unclear in patients with REM-related OSA. We studied 27 patients with REM-related OSA, categorized as having REM-apnea-hypopnea index (REM-AHI) ≥ 5/h, REM-AHI/non-REM-AHI ≥ 2, and non-REM-AHI < 15/h. Beat-to-beat systolic BP (SBP) variability and nocturnal SBP fluctuation patterns using pulse transit time (PTT) were investigated. The maximum increase and average nocturnal SBP were significantly higher in males than in females (p = 0.003 and p = 0.008, respectively). The rate of non-dipping patterns in nocturnal SBP fluctuations was 63% in all patients (males, 70%; females, 50%). Epworth Sleepiness Scale (ESS) and Self-rating Depression Scale (SDS) scores in females were higher than those in males (8.4 ± 6.1 vs. 13.4 ± 5.4 points, p = 0.04; 43.8 ± 7.9 vs. 52 ± 11.6 points, p = 0.04, respectively). A high proportion of patients with REM-related OSA had a non-dipping pattern. Using PPT, we observed that in patients with REM-related OSA, SBP variability was greater in males. Despite clinical symptoms being slightly more severe in females, nocturnal SBP fluctuations should be considered in male patients with REM-related OSA.

Understanding the Associations of Prenatal Androgen Exposure on Sleep Physiology, Circadian Proteins, Anthropometric Parameters, Hormonal Factors, Quality of Life, and Sex Among Healthy Young Adults: Protocol for an International, Multicenter Study.

BACKGROUND: The ratio of the second finger length to the fourth finger length (2D:4D ratio) is considered to be negatively correlated with prenatal androgen exposure (PAE) and positively correlated with prenatal estrogen. Coincidentally, various brain regions are sensitive to PAE, and their functions in adults may be influenced by the prenatal actions of sex hormones. OBJECTIVE: This study aims to assess the relationship between PAE (indicated by the 2D:4D ratio) and various physiological (sex hormone levels and sleep-wake parameters), psychological (mental health), and sexual parameters in healthy young adults. METHODS: This study consists of two phases. In phase 1, we will conduct a survey-based study and anthropometric assessments (including 2D:4D ratio and BMI) in healthy young adults. Using validated questionnaires, we will collect self-reported data on sleep quality, sexual function, sleep chronotype, anxiety, and depressive symptoms. In phase 2, a subsample of phase 1 will undergo polysomnography and physiological and genetic assessments. Sleep architecture data will be obtained using portable polysomnography. The levels of testosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, melatonin, and circadian regulatory proteins (circadian locomotor output cycles kaput [CLOCK], timeless [TIM], and period [PER]) and the expression levels of some miRNAs will be measured using blood samples. The rest and activity cycle will be monitored using actigraphy for a 7-day period. RESULTS: In Poland, 720 participants were recruited for phase 1. Among these, 140 completed anthropometric measurements. In addition, 25 participants joined and completed phase 2 data collection. Recruitment from other sites will follow. CONCLUSIONS: Findings from our study may help to better understand the plausible role of PAE in sleep physiology, mental health, and sexual quality of life in young adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29199.

Insomnia as a Symptom of Rapid Eye Movement-Related Obstructive Sleep Apnea.

Rapid eye movement (REM)-related obstructive sleep apnea (OSA), a polysomnographic phenotype that affects 12-36% of OSA patients, is defined by apnea and hypopnea events that predominantly or exclusively occur during REM sleep. Recent studies indicated that REM-related OSA was associated with the development of nocturnal non-dipping of systolic and diastolic blood pressure, metabolic syndrome, diabetes, and depressive symptoms. However, to date, the association between REM-related OSA and insomnia still remains unclear. We investigated whether there was a difference between REM- and non-REM-related OSA in terms of insomnia-related sleep disturbance as measured by the Pittsburgh Sleep Quality Index (PSQI) in 1736 patients with OSA. REM-related OSA showed a significant association with increased PSQI in all adjusted models. In the subgroup analysis, the coefficients of all models were higher in female than in male patients with REM-related OSA. Insomnia should be considered an important complaint in patients with REM-related OSA, and its indicators, such as the PSQI, should be included in routine diagnostic testing.

Treatment outcome of oral appliance in patients with REM-related obstructive sleep apnea.

PURPOSE: Oral appliances (OA) are used to treat patients with obstructive sleep apnea (OSA). The purpose of this study is to evaluate the efficacy of OA treatment in patients with rapid eye movement (REM)-related OSA. METHODS: Forty-six patients with REM-related OSA and 107 with non-stage-specific OSA were prescribed OA treatment after diagnosis by polysomnography (PSG) and a follow-up sleep test by PSG was conducted. Efficacy and treatment outcome predictors were evaluated according to the following criteria for treatment success: #1, reduction of the apnea-hypopnea index (AHI) to less than 5 and > 50% compared with baseline; #2, AHI reduction to less than 10 and > 50% compared with baseline; and #3, > 50% AHI reduction compared with baseline. RESULTS: Success rates according to criteria #1, #2, and #3 were 45.7%, 50.0%, and 50.0% in REM-related OSA and 36.4%, 52.3%, and 63.6% in non-stage-specific OSA, respectively. No significant differences in success rate were found between the two groups. In multivariate logistic regression analysis with each criterion as the response variable, only BMI was extracted as a significant predictor. The BMI cutoff values defined based on the maximum Youden index according to the three criteria were 26.2 kg/m2, 25.6 kg/m2, and 26.2 kg/m2, respectively. CONCLUSIONS: No significant differences in success rate of OA treatment were found between REM-related OSA and non-stage-specific OSA. BMI has greater impact on treatment outcome of OA in patients with REM-related OSA.

Impact of Gender and Age on Rapid Eye Movement-Related Obstructive Sleep Apnea: A Clinical Study of 3234 Japanese OSA Patients.

Rapid eye movement (REM)-related obstructive sleep apnea (OSA) is characterized by apnea and hypopnea events due to airway collapse occurring predominantly or exclusively during REM sleep. Previous studies have reported that REM-related OSA occurs more commonly in women and younger individuals. However, external validity of this tendency has not been confirmed in a large clinical sample. The objective of this study was to evaluate the effect of gender and age on REM-related OSA after adjustment for several covariates based on their established clinical relationships to gender difference in OSA. A total of 3234 Japanese patients with OSA were enrolled in this study. We confirmed that female sex is an important risk factor for REM-related OSA, as reported by previous studies. Moreover, we showed that women aged over 50 years were at a greater risk than those aged under 50 years. These results suggest that hormonal changes in women might play an important role in REM-related OSA and might reflect its unknown pathophysiological characteristics.

Prevalence of Rapid Eye Movement-related Obstructive Sleep Apnea in Adult Narcolepsy.

Objective The association between narcolepsy and rapid eye movement (REM)-related obstructive sleep apnea (OSA) has not been reported. This study aimed to examine the prevalence of REM-related OSA in narcolepsy patients. Methods From January 2013 to April 2018, 141 adult patients were diagnosed with narcolepsy using nocturnal polysomnography and the multiple sleep latency test. The prevalence of REM-related OSA in narcolepsy patients was retrospectively reviewed. Three criteria were used to determine REM-related OSA: Definition #1, an overall apnea-hypopnea index (AHI) ≥5 and AHI during REM (AHIREM)/AHI during non-rapid eye movement (NREM) (AHINREM) ≥2; Definition #2, an overall AHI ≥5 and AHIREM/AHINREM≥2 and AHINREM <15; and Definition #3, an overall AHI ≥5 and AHIREM/AHINREM≥2 and AHINREM <8 plus an REM sleep duration >10.5 minutes. Results Of the 141 narcolepsy patients, 26 were diagnosed with narcolepsy with cataplexy (NA-CA) and 115 with narcolepsy without cataplexy (NA w/o CA). Seventeen patients with NA-CA and 39 with NA w/o CA had OSA. According to Definition #1, the prevalence of REM-related OSA was 47.1% and 41.0%, respectively, in OSA patients with NA-CA and NA w/o CA; according to Definition #2, the respective prevalence was 47.1% and 38.5%, while that according to Definition #3 was 41.2% and 25.6%. No significant differences were found in the prevalence of REM-related OSA for each definition. Conclusion A high prevalence of REM-related OSA was confirmed in adult narcolepsy patients with OSA. Compared to previous reports, we noted a high frequency of REM-related OSA satisfying the relatively strict Definition #3. These results might reflect the pathophysiological characteristics of narcolepsy.

Effect of rapid eye movement-related obstructive sleep apnea on adherence to continuous positive airway pressure.

Objective Rapid eye movement (REM)-related obstructive sleep apnea (OSA) is characterized by respiratory events such as apnea and hypopnea predominately or exclusively during REM sleep. Several studies have revealed clinical predictors of adherence to the use of continuous positive airway pressure (CPAP). However, the effect of REM-related OSA on adherence to CPAP use remains unclear. Therefore, we investigated the effects of REM-related OSA on adherence to CPAP use 6 months after treatment initiation. Methods We enrolled 161 patients in this study and divided them into 3 groups: the good adherence, poor adherence, and dropout groups. We compared polysomnographic data and clinical findings, including those regarding morbidity of REM-related OSA, among the three groups to identify predictors of adherence to CPAP use. Results None of the 43 patients in the good adherence group had REM-related OSA. Multivariate logistic regression analysis of the good adherence and dropout groups indicated that REM-related OSA was the only factor associated with adherence to CPAP use (odds ratio, 41.984; 95% confidence interval, 2.257-781.007). Conclusions REM-related OSA is a reliable risk factor for dropout from CPAP therapy.

Polysomnographic parameters during non-rapid eye movement sleep predict continuous positive airway pressure adherence.

The aim of this study was to investigate the potential polysomnographic predictors of CPAP adherence using polysomnographic parameters at the time of obstructive sleep apnea diagnosis that distinguished between REM and NREM sleep. This was a retrospective cross-sectional study of 173 patients. Patients who used CPAP for more than 4 hours per night for at least 70% of nights over a 6-month period were considered to have good adherence. The poor adherence group included those who had used CPAP for 6 months from initiation, but did not fulfill the definition of good adherence or gave up the treatment within 6 months of treatment initiation. Of the 173 participants, 44 patients had good CPAP adherence and 129 patients had poor adherence. Univariate analysis showed that patients with good adherence had significantly higher apnea-hypopnea index during NREM sleep (p = 0.043), oxygen desaturation index during NREM sleep (p = 0.011), and cumulative percentage of time spent at saturations below 90% (CT90) during NREM sleep (p < .001). In multiple logistic regression analysis including all variables, CT90 during NREM sleep was the only factor independently associated with CPAP adherence (odds ratio, 0.693; 95% confidence interval, 0.582-0.824; p <.0001). The area under the receiver-operating characteristic curve of CT90 during NREM sleep was 0.823 (95% confidence interval, 0.745-0.901).Evaluating NREM sleep is important in reliably predicting CPAP adherence using polysomnographic parameters. CT90 during NREM sleep was the best predictor of CPAP adherence.

[Polysomnography].

Polysomnography (PSG) is performed under monitoring each parameters include EEG derivations, EOG derivations, chin EMG, leg EMG derivations, airflow signals, respiratory effort signals, oxygen saturation, body position and EGG and checking digital video and audio. From these recordings, the sleep quality, sleep-disordered breathing, circulatory status and presence of parasomnia were evaluated. PSGs were based on the criteria "The AASM Manual for the Scoring of Sleep and Associated Events" published in 2007 detailed about technical specification and scoring rules for adult and pediatric. However, there are no specific criteria for the elderly. There already have been known about characteristics for the elderly such as lower amplitude of Δ wave in slow-wave sleep stage, PLMS and RWA in PSG.

Risk factors for automobile accidents caused by falling asleep while driving in obstructive sleep apnea syndrome.

PURPOSE: We examined the risk factors for automobile accidents caused by falling asleep while driving in subjects with obstructive sleep apnea syndrome (OSAS). METHODS: We asked licensed drivers with history of snoring and excessive daytime sleepiness who had undergone polysomnography (PSG) at the Department of Sleep Medicine/Sleep Disorders Center at Aichi Medical University Hospital to complete the questionnaires on accidents caused by falling asleep while driving. As a subjective measure of sleepiness, we used the Epworth sleepiness scale (ESS). Based on PSG results, 2387 subjects diagnosed with OSAS were divided into three groups according to apnea-hypopnea index (AHI): mild-to-moderate (5 ≤ AHI < 30), severe (30 ≤ AHI < 60), and very severe (AHI ≥ 60). We performed univariate and multivariate logistic regression on variables that might explain falling asleep at the wheel. RESULTS: We compared results between each group and simple snorers (394 subjects with AHI < 5) and found the group with very severe OSAS reported significantly higher rates of driving when drowsy and having accidents in the past 5 years due to falling asleep. CONCLUSIONS: Our multivariate analysis suggests that scores on the ESS and patient-reported frequency of feeling drowsy while regular driving and working are related to automobile accidents caused by falling asleep while driving.

Association between pupillometric sleepiness measures and sleep latency derived by MSLT in clinically sleepy patients.

OBJECTIVES: The multiple sleep latency test (MSLT) has been employed extensively in clinical and research settings as a gold standard for objectively measuring sleepiness. In a general population or in a variety of work settings, however, a more convenient, rapidly administered measuring method is preferable. We examined the potential utility of pupillometry by comparing its objective measures, pupillary unrest index (PUI) and relative pupillary unrest index (RPUI), with MSLT-derived sleep latency (SL). METHODS: The study cohort comprised 45 patients (39 males, 6 females, mean age 38.9 ± 11.3 years) referred to the Sleep Disorders Center for the two-nap SL test. SL was measured twice before noon, and pupillometric measurement was performed immediately before each SL test. Subjective sleepiness was measured by using the Epworth Sleepiness Scale (ESS). RESULTS: The association between PUI and SL was significant and far closer than that between RPUI and SL. A significant difference was observed between the two groups, based on each subject's experience of drowsy driving accidents over the past 3 years in the PUI and RPUI, as well as in SL. The subjective sleepiness measure, ESS, did not relate to any other physiological sleepiness measures. CONCLUSIONS: In our study cohort, the pupillometric sleepiness measure, PUI, was significantly correlated with, and behaved in a manner equivalent to, MSLT-derived SL in clinically sleepy patients. However, several points remain to be carefully examined before applying pupillometry for screening sleepiness in a general population, or in occupational settings.

[A sleep disordered breathing as the lifestyle-related diseases].

Lifestyle related disease is a generic term for diseases such as cardiovascular diseases, diabetes mellitus and cancer caused by life style or life habit, and one of its fundamental causes is obesity. The reason why most people put on weight after their middle age is mainly because of the increase of visceral fat by the decrease in basal metabolism and the amount of momentum despite of unchanging appetite. Due to this sequence of weight gain, after middle age upper respiratory tract becomes narrower, and it worsens obstructive sleep apnea syndrome (OSAS). Since mastication is to provoke and maintain arousal, OSAS patients, who especially feel strong sleepiness, tend to encourage them to be obesity by frequent mastication that leads them to the tendency to overeat. Two main symptoms of OSAS are snoring and sleepiness; however, the essence of sleepiness is the worse quality of sleep due to apnea. In addition, a vicious circle is eventually generated because sleep deprivation and sleep disorders affects hypertension and glucose intolerance, and those worsen lifestyle disease. In order to break this off, it is necessary to review life style and habit, and improve not only on diet and exercise therapy but also on sleep.