The effect of nonrestorative sleep on incident hypertension 1-2 years later among middle-aged Hispanics/Latinos.

BACKGROUND: Insomnia is known to be a major risk factor for incident hypertension. Nonrestorative sleep (NRS), which refers to insufficiently rested sleep, has reported to associate with various diseases. This study aimed to investigate the longitudinal association between insomnia-related symptoms including NRS and incident hypertension 1-2 years later by age group (young, 18-39 years and middle-age, 40-64 years) using existing cohort data involving Hispanics/Latinos. METHODS: This study included 1100 subjects who had participated in both the Hispanic Community Health Study/Study of Latinos and its follow-up study, the Sueño Ancillary Study, and met additional eligibility criteria. Incident hypertension was assessed by self-reported history and/or the use of antihypertensives. The Women's Health Initiative Insomnia Rating Scale (WHIIRS) was used to evaluate insomnia-related symptoms (difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, difficulty returning to sleep, and NRS). Logistic regression analyses were conducted to assess the degree to which insomnia-related symptoms at baseline predicted incident hypertension. RESULTS: Among the participants (64% middle-aged, 36% young adults), 140 (12.7%) developed hypertension during the follow-up period. Among the sleep-related symptoms, only NRS predicted incident hypertension after adjusting for sociodemographic factors and physical condition (odds ratio: 1.88, 95% confidence interval: 1.10-3.21, p = 0.022) in middle-aged adults. None of the insomnia-related symptoms were associated with incident hypertension in the young adults. No association was found between WHIIRS-defined insomnia (total score ≥ 9) and incident hypertension in middle-aged adults or young adults. CONCLUSION: The present findings suggest the importance of focusing on NRS to help prevent the development of hypertension in middle-aged adults.

Associations of nonrestorative sleep and insomnia symptoms with incident depressive symptoms over 1-2 years: Longitudinal results from the Hispanic Community Health Study/Study of Latinos and Sueño Ancillary Study.

BACKGROUND: Nonrestorative sleep (NRS), defined as insufficiently rested or refreshed sleep, is considered to play an important role in the development of depression. The aim of this study is to investigate the predictive ability of insomnia-related symptoms, including NRS, for incident depressive symptoms (DEPs) in a longitudinal manner. METHODS: We used data of 1196 samples aged 18-64 years who participated in both the Hispanic Community Health Study/Study of Latinos conducted in 2008-2010 and the follow-up study (Sueño Ancillary Study) conducted in 2010-2013. DEPs and insomnia-related symptoms (difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], early morning awakening [EMA], difficulty returning to sleep [DRS], and NRS) were evaluated by the 10-item Center for Epidemiologic Studies Depression Scale and the Women's Health Initiative Insomnia Rating Scale, respectively. A logistic regression analysis was used to evaluate the predictive ability of each insomnia-related symptom at baseline for incident DEPs in couple-years. RESULTS: In the univariate logistic regression analysis, all insomnia-related symptoms had significant associations with incident DEPs (DIS, odds ratio [OR] = 1.6; DMS, OR = 1.6; EMA, OR = 1.5; DRS, OR = 1.9; NRS, OR = 2.5). After adjusting for sociodemographic factors and the confounding effects of other insomnia-related symptoms, only NRS (OR = 2.2, 95% confidence interval = 1.4-3.5, p = .001) was significantly associated with incident DEPs. CONCLUSIONS: NRS was a risk factor for incident DEPs, which includes a predictive ability for other insomnia-related symptoms. Our results suggest that focusing on NRS is an effective strategy for preventing depression in public health promotions.

Minor hallucinations in isolated rapid eye movement sleep behavior disorder indicative of early phenoconversion: A preliminary study.

OBJECTIVES: Minor hallucinations (MH) are psychotic symptoms that can occur anywhere between prodromal to early Parkinson's disease and after onset of motor problems. MH include visual illusions, presence hallucinations, and passage hallucinations. Isolated rapid eye movement sleep behavior disorder (RBD) is a harbinger of neurodegenerative diseases. We conducted a retrospective cohort study to investigate the clinical characteristics of isolated RBD with MH and the risk of phenoconversion. MATERIALS AND METHODS: We retrospectively analyzed the data of 36 patients with isolated RBD (four females; median age, 75.0 years). We defined cases reporting at least one minor hallucination as RBD with MH. Demographic data and cognitive function were compared between patients with and without MH, and Cox proportional hazards models estimated the risk of phenoconversion. RESULTS: We included 10 (27.8%) patients with MH and 26 (72.2%) without MH. Patients with MH were older, had less dopamine transporter accumulation, more severe autonomic dysfunction, more depressive symptoms, and lower verbal fluency and symbol coding test scores than patients without MH. After follow-up (median, 2.50 years), 13.9% (5/36) of all patients developed phenoconversion (Parkinson's disease, two patients; dementia with Lewy bodies, three patients). The rate of phenoconversion was significantly higher in patients with MH (40.0% vs. 3.8%, p = .005). The Cox proportional hazards model adjusted for age, sex, and disease duration revealed that MH was a significant risk factor for phenoconversion (hazard ratio, 14.72; 95% confidence interval, 1.35-160.5). CONCLUSIONS: Minor hallucinations may be utilized as early clinical markers for prodromal estimation of neurodegenerative diseases.

Explosive sound without external stimuli following electroencephalography kappa rhythm fluctuation: A case report.

BACKGROUND: The pathology underlying exploding head syndrome, a parasomnia causing a loud sound/sense of explosion, is not well understood. Kappa rhythm is a type of electroencephalogram alpha band activity with maximum potential between contralateral temporal electrodes We report a case of preceding kappa activity before exploding head syndrome attacks. CASE REPORT: A 57-year-old woman complained of explosive sounds for 2 months; a loud sound would transpire every day before sleep onset. She was diagnosed with exploding head syndrome. During polysomnography and the multiple sleep latency test, the exploding head syndrome attacks occurred six times. A kappa wave with activity disappearing a few seconds before most exploding head syndrome attacks was observed. The alpha band power in T3-T4 derivation gradually waxed followed by termination around the attacks. CONCLUSION: This case demonstrated that the dynamics of kappa activity precede exploding head syndrome attacks. Finding ways to modulate electroencephalogram oscillation could elucidate their causality and lead to therapeutic intervention.

Association between discontinuation of benzodiazepine receptor agonists and post-operative delirium among inpatients with liaison intervention: A retrospective cohort study.

BACKGROUND: Several studies have investigated the association between benzodiazepine receptor agonist (BZDRA) use during the perioperative period and an elevated incidence of delirium. However, no study has focused on the time course of BZDRA use, including continuation, discontinuation, initiation, and no use. This study aimed to examine the influence of the time course of BZDRA use on post-operative delirium. METHODS: This retrospective cohort study was conducted by reviewing medical records. We included patients who were scheduled for surgery under general anesthesia and had been referred to a liaison psychiatrist for pre-operative psychiatric assessment. The patients were classified into four groups based on the pre- and post-operative time course of oral BZDRA use, as follows: continuation, discontinuation, initiation, and no use (never used). The primary outcome was the prevalence of post-operative delirium in non-intensive care unit settings. We also performed stratified analyses according to age, the presence of cognitive impairment, the presence of delirium history, and antipsychotic drug use on admission. RESULTS: Among 250 patients, 78 (31%) developed post-operative delirium. The Discontinuation group had a higher rate of delirium (49%, 24/49) than the other groups (Continuation [14%, 4/29]; Initiation [38%, 3/8], Never used [29%, 47/164], p = 0.008). CONCLUSIONS: Abrupt discontinuation of BZDRAs during the perioperative period may be a risk factor for post-operative delirium and should therefore be avoided.

Screening of sleep apnea based on heart rate variability and long short-term memory.

PURPOSE: Sleep apnea syndrome (SAS) is a prevalent sleep disorder in which apnea and hypopnea occur frequently during sleep and result in increase of the risk of lifestyle-related disease development as well as daytime sleepiness. Although SAS is a common sleep disorder, most patients remain undiagnosed because the gold standard test polysomnography (PSG), is high-cost and unavailable in many hospitals. Thus, an SAS screening system that can be used easily at home is needed. METHODS: Apnea during sleep affects changes in the autonomic nervous function, which causes fluctuation of the heart rate. In this study, we propose a new SAS screening method that combines heart rate measurement and long short-term memory (LSTM) which is a type of recurrent neural network (RNN). We analyzed the data of intervals between adjacent R waves (R-R interval; RRI) on the electrocardiogram (ECG) records, and used an LSTM model whose inputs are the RRI data is trained to discriminate the respiratory condition during sleep. RESULTS: The application of the proposed method to clinical data showed that it distinguished between patients with moderate-to-severe SAS with a sensitivity of 100% and specificity of 100%, results which are superior to any other existing SAS screening methods. CONCLUSION: Since the RRI data can be easily measured by means of wearable heart rate sensors, our method may prove to be useful as an SAS screening system at home.

Effects of Cognitive Behavioral Therapy for Insomnia on Subjective-Objective Sleep Discrepancy in Patients with Primary Insomnia: a Small-Scale Cohort Pilot Study.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia METHODS: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1-2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I. RESULTS: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy. CONCLUSIONS: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies.

A missense variant in PER2 is associated with delayed sleep-wake phase disorder in a Japanese population.

Delayed sleep-wake phase disorder (DSWPD) is a subtype of circadian rhythm sleep-wake disorders, and is characterized by an inability to fall asleep until late at night and wake up at a socially acceptable time in the morning. The study aim was to identify low-frequency nonsense and missense variants that are associated with DSWPD. Candidate variants in circadian rhythm-related genes were extracted by integration of genetic variation databases and in silico assessment. We narrowed down the candidates to six variants. To examine whether the six variants are associated with DSWPD, we performed an association study in 236 Japanese patients with DSWPD and 1436 controls. A low-frequency missense variant (p.Val1205Met) in PER2 showed a significant association with DSWPD (2.5% in cases and 1.1% in controls, P = 0.026, odds ratio (OR) = 2.32). The variant was also associated with idiopathic hypersomnia known to have a tendency toward phase delay (P = 0.038, OR = 2.07). PER2 forms a heterodimer with CRY, and the heterodimer plays an important role in the regulation of circadian rhythms. Val1205 is located in the CRY-binding domain of PER2 and was hypothesized to interact with CRY. The p.Val1205Met substitution could be a potential genetic marker for DSWPD.

Non-REM sleep-disordered breathing affects performance on the psychomotor vigilance task.

PURPOSE: Although many studies have investigated the clinical importance of sleep apnea on rapid eye movement (REM) and non-REM (NREM) sleep, the relationship between behavioral performance and apneic events during different sleep phases remains unclear. In the present study, we sought to investigate the effect of sleep phase fragmentation due to sleep-disordered breathing (SDB) during REM and NREM on the vigilance and sustainability of attention based on psychomotor vigilance task (PVT) performance. METHODS: From a pool of subjects who underwent consecutive diagnostic polysomnography (PSG) for obstructive sleep apnea, 163 adult subjects with both REM and NREM sleep ≥ 30 min were enrolled for our study and performed a standardized 10-min PVT. The main outcome variables of the PVT were mean reaction time (RT), PVT Lapse count, and the slope of the reciprocal RT. Subjective sleepiness was measured using the Epworth Sleepiness Scale (ESS). RESULTS: After multivariate linear regression analysis with adjustment for age, sex, body mass index, and the apnea-hypopnea index (AHI) of the counterpart sleep phase, we found that AHI during NREM (AHINREM) compared to AHI during REM (AHIREM) was significantly associated with PVT lapses. CONCLUSIONS: Our results suggest that SDB during NREM has a significant impact on vigilance lapses compared to that of REM.

Association of sleep-disordered breathing with decreased cognitive function among patients with dementia.

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type-4 portable monitor, is suitable. In this study, a type-4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep-disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep-disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early-stage dementia.

Associations among chronic obstructive pulmonary disease and sleep-disordered breathing in an urban male working population in Japan.

BACKGROUND: There are few reports about sleep disturbances in patients with chronic obstructive pulmonary disease (COPD) in Asian countries. OBJECTIVES: To investigate the associations between sleep-disordered breathing (SDB) with hypoxemia and sleep quality, including sleep duration, in patients with COPD, we measured SDB and sleep quality including the objective sleep duration determined by an actigraph and portable monitoring. METHODS: A cross-sectional epidemiological health survey of 303 male employees (means ± SD: age 43.9 ± 8.2 years; BMI 24.0 ± 3.1) was conducted. Sleep quality was measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). A respiratory disturbance index (RDI) ≥5 indicated SDB. RESULTS: Nineteen subjects (6.3%) had COPD. Among these, 11 (3.6%) had COPD with SDB (overlap syndrome). Sleep duration, ESS, and PSQI scores were not significantly different between COPD patients and normal control subjects. However, COPD patients had significantly longer sleep latency (p = 0.019), a lower sleep efficiency (p = 0.017), and a higher sleep fragmentation index (p = 0.041) and average activity (p = 0.0097) during sleep than control subjects. They also had a significantly higher RDI and more severe desaturation during sleep than control subjects (p < 0.01). The differences remained after adjustment for age and BMI but disappeared following adjustment for RDI. CONCLUSIONS: COPD patients with even mild-to-moderate airflow limitations had nocturnal desaturation and RDI-related impaired sleep quality without significant symptoms.

Prevalence of obstructive sleep apnea syndrome in Japanese elementary school children aged 6-8 years.

PURPOSE: We aimed to determine the prevalence of and the risk factors for obstructive sleep apnea syndrome (OSAS) in Japanese children aged 6-8 years. METHODS: The parents of 202 children aged 6-8 years who attended a single elementary school in Shiga, Japan, were requested to complete the Child and Adolescent Sleep Checklist (CASC) and perform home Type 3 portable monitoring of their children. By using the CASC data and monitor recordings, we estimated the prevalence of pediatric OSAS with the help of different diagnostic criteria and identified the risk factors associated with OSAS. RESULTS: Complete data were obtained from 170 of the 194 children whose parents participated in the study. The mean total apnea-hypopnea index and obstructive apnea hypopnea index were 1.4 ± 1.3 and 0.4 ± 0.6 h(-1), respectively, and central apnea was the most prevalent type of respiratory event, accounting for 70.4% of all events. The overall prevalence of OSAS ranged from 0.6% to 43.5%, depending on the cutoff value used, and was 3.5% when using International Criteria of Sleep Disorders version II (ICSD II) diagnostic criteria. The presence of tonsillar hypertrophy was the only parameter whose prevalence was significantly elevated in children with OSAS across all diagnostic criteria. CONCLUSIONS: The prevalence of pediatric OSAS varies according to the diagnostic criteria used, indicating the need for further research focusing on outcomes to define a clinically significant diagnostic threshold. The presence of tonsillar hypertrophy is an important risk factor in the development of pediatric OSAS.

The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study.

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Mapping the landscape of sleep medicine training across Asia.

STUDY OBJECTIVES: This study assessed the current state of sleep medicine accreditation and training in Asia by conducting a comprehensive survey across 29 Asian countries and regions facilitated by the Asian Society of Sleep Medicine (ASSM) to identify existing gaps and provide recommendations for future enhancements. METHODS: The ASSM Education Task Force Committee designed a survey to gather data on accreditation, education, and training standards in sleep medicine, including information on challenges in enhancing education in the field. RESULTS: With an 86% (25 countries/regions) response rate, the survey showed that sleep medicine is recognized as an independent specialty in just nine countries/regions (36% of the countries/regions surveyed). Ten countries/regions have established sleep medicine training programs, with Japan and Saudi Arabia offering it as a distinct specialty. Significant disparities in training and accreditation standards were identified, with many countries/regions lacking formalized training and practice guidelines. The survey also revealed that most local sleep societies across Asia support the development of an Asian Sleep Medicine Training Curriculum led by the ASSM. However, several barriers significantly impede the establishment and development of sleep medicine training programs, including the scarcity of trained specialists and technologists and the absence of national accreditation for sleep medicine. CONCLUSIONS: The survey highlights the need for standardized sleep medicine training and accreditation across Asia. Developing an Asian Sleep Medicine Training Curriculum and promoting ASSM accreditation guidelines are key recommendations. Implementing these strategies is essential for advancing sleep medicine as a widely recognized discipline throughout Asia.

Circadian clock-controlled diurnal oscillation of Ras/ERK signaling in mouse liver.

Accumulating evidence indicates that ERK MAP kinase signaling plays an important role in the regulation of the circadian clock, especially in the clock-resetting mechanism in the suprachiasmatic nucleus (SCN) in mammals. Previous studies have also shown that ERK phosphorylation exhibits diurnal variation in the SCN. However, little is known about circadian regulation of ERK signaling in peripheral tissues. Here we show that the activity of Ras/ERK signaling exhibits circadian rhythms in mouse liver. We demonstrate that Ras activation, MEK phosphorylation, and ERK phosphorylation oscillate in a circadian manner. As the oscillation of ERK phosphorylation is lost in Cry1/Cry2 double-knockout mice, Ras/ERK signaling should be under the control of the circadian clock. Furthermore, expression of MAP kinase phosphatase-1 (Mkp-1) shows diurnal changes in liver. These results indicate that Ras/ERK signaling is strictly regulated by the circadian clock in liver, and suggest that the circadian oscillation of the activities of Ras, MEK, and ERK may regulate diurnal variation of liver function and/or homeostasis.(Communicated by Shigekazu NAGATA, M.J.A.).

Association of Sleep Reactivity and Anxiety Sensitivity with Insomnia-Related Depression and Anxiety among City Government Employees in Japan.

It has recently been noted that a reduction in sleep reactivity, characterized as the trait-like degree to which exposure to stress interferes with sleep, and anxiety sensitivity are associated with reduced insomnia severity. This study aimed to examine whether sleep reactivity and anxiety sensitivity are associated with insomnia-related depression and anxiety among city government employees in Japan. This cross-sectional study included 1810 city government employees of Koka City, Japan (mean age (standard deviation): 45.33 (12.20) years) who completely answered the scales for sleep reactivity, anxiety sensitivity, anxiety, and depression. Stepwise multiple regression analysis adjusted for demographic data showed that anxiety sensitivity (ß = 0.39) was significantly linked to anxiety, and sleep reactivity (ß = 0.36) was significantly linked to depression in individuals with insomnia. Additionally, the results of a logistic regression analysis adjusted for demographic data showed that anxiety sensitivity and sleep reactivity were relevant factors for anxious insomnia (OR = 12.69) and depressive insomnia (OR = 8.73), respectively. Whereas both sleep reactivity (OR = 14.67) and anxiety sensitivity (OR = 6.14) were associated with combined insomnia. These findings indicate that sleep reactivity is strongly associated with depressive symptoms, and anxiety sensitivity is strongly associated with anxiety symptoms in individuals with insomnia.

Correction to: Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography.

[This corrects the article DOI: 10.1007/s41105-022-00421-5.].

Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography.

Automatic algorithms are a proposed alternative to manual assessment of polysomnography data for analyzing sleep structure; however, none are acceptably accurate for clinical use. We investigated the feasibility of an automated sleep stage scoring system called Sleep Scope, which is intended for use with portable 1-channel electroencephalograph, and compared it with the traditional polysomnography scoring method. Twenty-six outpatients and fourteen healthy volunteers underwent Sleep Scope and polysomnography assessments simultaneously. Polysomnography records were manually scored by three sleep experts. Sleep Scope records were scored using a dedicated auto-staging algorithm. Sleep parameters, including total sleep time, sleep latency, wake after sleep onset, and sleep efficiency, were calculated. The epoch-by-epoch pairwise concordance based on the classification of sleep into five stages (i.e., wake, rapid eye movement, N1, N2, and N3) was also evaluated after validating homogeneity and bias between Sleep Scope and polysomnography. Compared with polysomnography, Sleep Scope seemed to overestimate sleep latency by approximately 3 min, but there was no consistent tendency in bias in other sleep parameters. The Κ values ranged from 0.66 to 0.75 for experts' inter-rater polysomnography scores and from 0.62 to 0.67 for Sleep Scope versus polysomnography scores, which indicated sufficient agreement in the determination of sleep stages based on the Landis and Koch criteria. We observed sufficient concordance between Sleep Scope and polysomnography despite lower concordance in sleep disorder patients. Thus, this auto-staging system might serve as a novel clinical tool for reducing the time and expenses required of medical staff and patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00421-5.