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Abstract Feeling awake although sleep recordings indicate clear-cut sleep sometimes occurs in good sleepers and to an extreme degree in patients with so-called paradoxical insomnia. It is unknown what underlies sleep misperception, as standard polysomnographic (PSG) parameters are often normal in these cases. Here we asked whether regional changes in brain activity could account for the mismatch between objective and subjective total sleep times (TST). To set cutoffs and define the norm, we first evaluated sleep perception in a population-based sample, consisting of 2,092 individuals who underwent a full PSG at home and estimated TST the next day. We then compared participants with a low mismatch (normoestimators, n = 1,147, ±0.5 SD of mean) with those who severely underestimated (n = 52, <2.5th percentile) or overestimated TST (n = 53, >97.5th percentile). Compared with normoestimators, underestimators displayed higher electroencephalographic (EEG) activation (beta/delta power ratio) in both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, while overestimators showed lower EEG activation (significant in REM sleep). To spatially map these changes, we performed a second experiment, in which 24 healthy subjects and 10 insomnia patients underwent high-density sleep EEG recordings. Similarly to underestimators, patients displayed increased EEG activation during NREM sleep, which we localized to central-posterior brain areas. Our results indicate that a relative shift from low- to high-frequency spectral power in central-posterior brain regions, not readily apparent in conventional PSG parameters, is associated with underestimation of sleep duration. This challenges the concept of sleep misperception, and suggests that instead of misperceiving sleep, insomnia patients may correctly perceive subtle shifts toward wake-like brain activity.

Study Objectives Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with neurodegenerative synucleinopathies. Its prevalence is largely unknown. This study determined the prevalence and characteristics of RBD in the general population using gold-standard polysomnography. Methods Full polysomnographic data from 1,997 participants (age = 59 ± 11.1 years, 53.6% women) participating in a population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Sleep-related complaints and habits were investigated using various sleep measures including the Munich Parasomnia Screening (MUPS) questionnaire, which includes two questions evaluating complex motor behaviors suggestive of RBD. Full polysomnography was performed at home. For participants screening positive for RBD, muscle activity during REM sleep was quantified to diagnose RBD. Results Three hundred sixty-eight participants endorsed dream-enactment behavior on either of the two MUPS questions, and 21 fulfilled polysomnographic criteria for RBD, resulting in an estimated prevalence of 1.06% (95% CI = 0.61–1.50), with no difference between men and women. Compared with RBD− participants, RBD+ took more frequently antidepressants and antipsychotics (23.8% vs. 5.4%, p = .005; 14.3% vs. 1.5%, p = .004, respectively) and were more frequently smokers or ex-smokers (85% vs. 56.6%, p = .011). On polysomnography, RBD+ had more stage N2 sleep (52 ± 11.5% vs. 46.3 ± 10.2%, p = .024) and less REM sleep (18 ± 6.4% vs. 21.9 ± 6.2%, p = .007), lower apnea–hypopnea index in REM sleep (3.8 ± 5.2 vs. 8.9 ± 13/hour, p = .035), and lower autonomic arousal index (31 ± 14.9 vs. 42.6 ± 19.5/hour, p = .002). Conclusions In our middle-to-older age population-based sample, the prevalence of RBD was 1.06%, with no difference between men and women. RBD was associated with antidepressant and antipsychotic use and with minor differences in sleep structure.

Although several studies have linked short and long sleep duration to weight gain, mixed results exist. Contrarily, few studies associated objectively measured sleep characteristics with weight gain. We investigated the association between several sleep characteristics measured by questionnaire and polysomnography with prospective weight gain in a population-based, middle-aged cohort. Three samples were analyzed: sample 1 (n = 2551, 47.3% men, 56.9 ± 10.3 years) had data for subjective sleep characteristics, sample 2 (n = 1422, 49.4% men, 57.6 ± 10.4 years) had objective sleep assessment (polysomnography), and sample 3 consisting of 1259 subjects included in both samples. Multivariable logistic regressions were performed to assess the relationship between sleep characteristics and ≥5 kg weight gain during a median follow-up of 5.3 years. In both study samples, 12% of the subjects gained ≥5 kg during follow-up. Multivariable analyses showed poor subjective sleep quality (as assessed by Pittsburgh Sleep Quality Index: odds ratio [95% confidence interval] = 1.54 [1.19 to 1.99]), percentage of sleep spent in stage 2 (1.32 [1.10 to 1.58]), and less than 90% oxygen saturation (SpO2 < 90) (1.23 [1.07 to 1.41]); moderate/severe Oxygen Desaturation Index (1.70 [1.01 to 2.85]) and autonomic arousal duration (1.22 [1.02 to 1.45]) were related to ≥5 kg weight gain. Only poor subjective sleep quality was robustly associated with weight gain in all sensitivity analyses, except in female subsamples. Poor subjective sleep quality, and to some extent moderate to severe oxygen desaturation, but no other sleep characteristics, were robustly associated with weight gain. Future studies should confirm the relationship between sleep quality and weight gain, assess sex differences, and investigate underlying mechanisms.

Study Objectives:To evaluate continuous positive airway pressure (CPAP) treatment in patients with moderate to severe sleep-disordered breathing (SDB) after an ischemic stroke.Methods:We identified patients included in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent polysomnography after an ischemic stroke. We compared patients without significant SDB (apnea-hypopnea index [AHI] < 15 events/h: SDB−), with AHI ≥ 15 events/h who refused CPAP or with poor CPAP adherence (SDB+ CPAP−), and patients with SDB effectively treated by CPAP (SDB+ CPAP+).Results:We analyzed data from 101 patients (age 68.5 ± 11.1 years, 84.1% men). In multivariate analysis the SDB+ CPAP+ group was associated with a significant reduction of stroke recurrence and mortality (odds ratio 0.13, 95% confidence interval 0.00–0.86, P = .031), whereas atrial fibrillation was independently associated with a higher risk (odds ratio 4.32, 95% confidence interval 1.51–12.33, P = .006). Event-free survival analysis (stroke recurrence and death) after 2-year follow-up showed that those in the SDB+ CPAP+ group had significantly higher cardiovascular survival, and Cox proportion hazard model identified CPAP treatment as significantly associated with survival time (P = .025). The AHI and the National Institutes of Health Stroke Scale subacute score were independently associated with CPAP adherence among patients with SDB.Conclusions:This observational study shows that CPAP treatment in stroke patients with moderate to severe SDB is associated with lower rates of stroke recurrence and death.Citation:Haba-Rubio J, Vujica J, Franc Y, Michel P, Heinzer R. Effect of CPAP treatment of sleep apnea on clinical prognosis after ischemic stroke: an observational study. J Clin Sleep Med 2019;15(6):839–847.

Background Sleep spindles have been involved in sleep stabilization and sleep-related memory mechanisms and their deficit emerged as possible biomarker in schizophrenia. However, whether this sleep phenotype is also present in other disorders that share psychotic symptoms remains unclear. To address this gap, we assessed sleep spindles in participants of a prospective population-based cohort who underwent psychiatric assessment (CoLaus|PsyCoLaus) and polysomnographic recording (HypnoLaus). Methods Sleep was recorded using ambulatory polysomnography in participants ( N  = 1037) to the PsyCoLaus study. Sleep spindle parameters were measured in people with a lifelong diagnosis of schizophrenia (SZ), schizoaffective depressive (SAD), schizoaffective manic (SAM), bipolar disorder type I (BP-I) and type II (BP-II). The associations between lifetime diagnostic status (independent variables, SZ, SAD, SAM, BPD-I, BPD-II, controls) and spindle parameters (dependent variables) including density, duration, frequency and maximum amplitude, for all (slow and fast), slow- and fast-spindle were assessed using linear mixed models. Pairwise comparisons of the different spindle parameters between the SZ group and each of the other psychiatric groups was performed using a contrast testing framework from our multiple linear mixed models. Results Our results showed a deficit in the density and duration of sleep spindles in people with SZ. They also indicated that participants with a diagnosis of SAD, SAM, BP-I and BP-II exhibited different sleep spindle phenotypes. Interestingly, spindle densities and frequencies were different in people with a history of manic symptoms (SAM, BP-I, and BP-II) from those without (SZ, SAD). Conclusions Although carried out on a very small number of participants due to the low prevalence of these disorders in general population, this pilot study brought new elements that argued in favor of a deficit of sleep spindles density and duration in people with schizophrenia. In addition, while we could expect a gradual change in intensity of the same sleep spindle parameters through psychotic diagnoses, our results seem to indicate a more complex situation in which the frequency of sleep spindles might be more impacted by diagnoses including a history of mania or hypomania. Further studies with a larger number of participants are required to confirm these effects.

Study Objectives:Apnea-hypopnea index (AHI) is the main polysomnographic measure to diagnose obstructive sleep apnea (OSA). We aimed to evaluate the effect of three standard hypopnea definitions on the prevalence of OSA and its association with cardiometabolic outcomes in the general population.Methods:We analyzed data from the HypnoLaus study (Lausanne, Switzerland), in which 2,162 participants (51% women, 57 ± 19 years) underwent in-home full polysomnography. AHI was calculated using three hypopnea definitions: AASM1999 (≥ 50% decrease in airflow or lower airflow reduction associated with oxygen desaturation ≥ 3% or an arousal), AASM2007 (≥ 30% airflow reduction associated with ≥ 4% oxygen desaturation), and AASM2012(≥ 30% airflow reduction associated with ≥ 3% oxygen desaturation or an arousal). Participants underwent clinical assessment for hypertension, diabetes, and metabolic syndrome.Results:Median AHI of AASM1999, AASM2007 and AASM2012 criteria were 10.9, 4.4, and 10.1 events/h, respectively. OSA prevalence defined as AHI ≥ 5, ≥ 15, and ≥ 30 events/h was 74.5%, 39.3%, and 16.3% using AASM1999; 46.9%, 18.8%, and 6.8% using AASM2007; and 72.2%, 36.6%, and 14.9% using AASM2012. Different AHI thresholds derived from AASM1999, AASM2007, and AASM2012 criteria, respectively, were associated with hypertension (11.5, 4.8, 10.7 events/h), diabetes (15.7, 7.1, 14.4 events/h), and metabolic syndrome (12.8, 5.5, 11.8 events/h).Conclusions:Hypopnea definition has a major effect on AHI and on OSA prevalence in the general population and, hence, important implications for public health policies. There is a twofold difference in the threshold above which an association with diabetes, hypertension, and metabolic syndrome is observed using AASM2007 compared to AASM1999 or AASM2012 criteria.Citation:Hirotsu C, Haba-Rubio J, Andries D, Tobback N, Marques-Vidal P, Vollenweider P, Waeber G, Heinzer R. Effect of three hypopnea scoring criteria on OSA prevalence and associated comorbidities in the general population. J Clin Sleep Med 2019;15(2):183–194.

Abstract Study Objectives Although recent investigations combining noradrenergic and antimuscarinic drugs have shown promising short-term results to treat obstructive sleep apnea (OSA), the mid-term effect and optimal dosage remain uncertain. The present study aimed to evaluate the effect of 1 week of 5 mg oxybutynin and 6 mg reboxetine (oxy-reb) on OSA versus placebo. Methods We performed a randomized, placebo-controlled, double-blind, crossover trial comparing the effect of 1 week of oxy-reb versus 1 week of placebo on OSA severity. At-home polysomnography was performed at baseline and after each week of intervention. Results Fifteen participants (male 66.7%) aged 59 [44–62] years (median [interquartile range]) with a mean body mass index of 33.1 ± 6.6 kg/m2 were included. No significant difference in apnea–hypopnea index (AHI) was observed between conditions (estimated marginal means [95% confidence interval] at baseline: 39.7 [28.5–55.3]; oxy-reb: 34.5 [22.7–52.3]; placebo: 37.9 [27.1–52.9]; p = 0.652), but oxy-reb improved average oxygen desaturation (p = 0.016) and hypoxic burden (p = 0.011) and lowered sleep efficiency (p = 0.019) and rapid eye movement sleep (p = 0.002). Moreover, participants reported reduced sleep quality during the week of oxy-reb compared to the week of placebo (4.7 [3.5; 5.9] vs. 6.5 [5.5; 7.5] on a 0–10 visual analogic scale, respectively; p = 0.001). No significant differences in sleepiness, vigilance, and fatigue were observed. No serious adverse events occurred. Conclusions Administration of oxybutynin 5 mg and reboxetine 6 mg did not improve OSA severity assessed by AHI, but did alter sleep architecture and sleep quality. Reduced average oxygen desaturation and hypoxic burden were also observed. Clinical Trial ClinicalTrials.gov, https://clinicaltrials.gov, NCT04394143. Graphical abstract Graphical Abstract

Background Workplace telepressure and private life telepressure refer to the preoccupation with and the urge to respond quickly to electronic messages from people at work or in private life, respectively. We aimed to adapt and validate workplace and private life telepressure measures in French and to explore their nomological networks and relationships with psychological health and wellbeing. Methods Participants were recruited via flyers, local press, and social media to complete two online surveys. Participants had to be French-speaking employees working in Switzerland and regularly using information and communication technologies for work purposes. The sample included 347 employees (200 females, 146 males, one nonbinary individual; mean age: 36.8 years) who completed both surveys. The first questionnaire assessed sociodemographic characteristics and the workplace and private life telepressure measures. The second questionnaire, which was administered approximately two weeks later, assessed complementary sociodemographic characteristics, nomologicals (five technostress creators, workaholism, neuroticism, conscientiousness, and mindfulness), measures of psychological health and wellbeing (depression, anxiety, stress, and psychological detachment from work), and the two telepressure measures. Results Both telepressure measures exhibited strong psychometric properties, including validity, reliability, and measurement invariance across age, gender, and time. Confirmatory factor analysis revealed that the two-factor model (preoccupation and urge factors) provided a better fit than did the one-factor model for both measures. Correlation analyses revealed that both telepressure measures were significantly positively associated with techno-invasion, techno-complexity, techno-insecurity, workaholism, and neuroticism and negatively associated with mindfulness. However, only workplace telepressure was significantly associated with techno-overload, and neither telepressure measure was significantly associated with techno-uncertainty. Structural equation modeling showed that workplace telepressure significantly predicted stress, anxiety, depression, and psychological detachment from work, whereas private life telepressure significantly predicted stress, anxiety, and psychological detachment from work, but not depression. Most effects were significantly greater for workplace telepressure than for private life telepressure. Conclusions This study confirms the validity of the workplace telepressure and private life telepressure measures for use in French-speaking populations and contributes to our understanding of the role of these two constructs in employees' psychological health and wellbeing.

Abstract Study Objectives Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects. Methods The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization. Results We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10−12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10−22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS. Conclusions Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Background The daily working life of many employees requires the use of modern information and communication technology (ICT) devices such as computers, tablets, and smartphones. The double-edged nature of digital work environments has been increasingly highlighted. Benefits such as increased flexibility come at a personal cost. One of the potential downsides is workplace telepressure, i.e., the experience of urge and preoccupation to quickly reply to work-related messages and demands using ICT. There is initial − mainly survey-based−evidence that workplace telepressure may have negative effects on a variety of wellbeing and health outcomes. Aims and hypotheses Adopting the Effort-Recovery Model and the concept of allostatic load as theoretical frameworks, the present study aims to investigate the hypothesis that workplace telepressure is significantly associated with increased “wear and tear”, in the form of more psychosomatic complaints, worse sleep quality (self-reported and actigraphy-based), worse mood, and biological alterations (lower cardiac vagal tone, lower anabolic balance defined as the ratio of salivary dehydroepiandrosterone to salivary cortisol, and higher salivary alpha-amylase). Additionally, the study aims to investigate the hypothesis that connection to work defined as work-related workload and work-related perseverative cognition plays a significant role in the mediation of these relationships. Methods To test our hypotheses, we will conduct an ambulatory assessment study with a convenience sample of 120 healthy workers regularly using ICTs for job communication. For one week, participants will be asked to complete electronic diaries assessing their level of workplace telepressure, psychosomatic complaints, sleep quality, mood, work-related workload, and work-related perseverative cognition. They will also continuously wear the Bittium Faros 180L ECG monitor, the wrist-worn actigraph MotionWatch 8, and perform saliva sampling five times per day. Discussion This study will be the most comprehensive ambulatory investigation of workplace telepressure and its psychophysiological concomitants to date and constitutes an important step towards understanding how high levels of workplace telepressure may lead in the long term to secondary alterations (e.g., hypertension, chronic inflammation) and disease (e.g., heart disease). The findings of this study are also anticipated to contribute to guiding the development and implementation of interventions, programs, and policies relevant to employees’ digital wellbeing.