Showing papers in "Journal of Sleep Research in 2022"

Insomnia disorder: State of the science and challenges for the future

Abstract: Insomnia disorder comprises symptoms during night and day that strongly affect quality of life and wellbeing. Prolonged sleep latency, difficulties to maintain sleep and early morning wakening characterize sleep complaints, whereas fatigue, reduced attention, impaired cognitive functioning, irritability, anxiety and low mood are key daytime impairments. Insomnia disorder is well acknowledged in all relevant diagnostic systems: Diagnostic and Statistical Manual of the American Psychiatric Association, 5th revision, International Classification of Sleep Disorders, 3rd version, and International Classification of Diseases, 11th revision. Insomnia disorder as a chronic condition is frequent (up to 10% of the adult population, with a preponderance of females), and signifies an important and independent risk factor for physical and, especially, mental health. Insomnia disorder diagnosis primarily rests on self‐report. Objective measures like actigraphy or polysomnography are not (yet) part of the routine diagnostic canon, but play an important role in research. Disease concepts of insomnia range from cognitive‐behavioural models to (epi‐) genetics and psychoneurobiological approaches. The latter is derived from knowledge about basic sleep–wake regulation and encompass theories like rapid eye movement sleep instability/restless rapid eye movement sleep. Cognitive‐behavioural models of insomnia led to the conceptualization of cognitive‐behavioural therapy for insomnia, which is now considered as first‐line treatment for insomnia worldwide. Future research strategies will include the combination of experimental paradigms with neuroimaging and may benefit from more attention to dysfunctional overnight alleviation of distress in insomnia. With respect to therapy, cognitive‐behavioural therapy for insomnia merits widespread implementation, and digital cognitive‐behavioural therapy may assist delivery along treatment guidelines. However, given the still considerable proportion of patients responding insufficiently to cognitive‐behavioural therapy for insomnia, fundamental studies are highly necessary to better understand the brain and behavioural mechanisms underlying insomnia. Mediators and moderators of treatment response/non‐response and the associated development of tailored and novel interventions also require investigation. Recent studies suggest that treatment of insomnia may prove to add significantly as a preventive strategy to combat the global burden of mental disorders.

The two‐process model of sleep regulation: Beginnings and outlook

Abstract: The two‐process model serves as a major conceptual framework in sleep science. Although dating back more than four decades, it has not lost its relevance for research today. Retracing its origins, I describe how animal experiments aimed at exploring the oscillators driving the circadian sleep–wake rhythm led to the recognition of gradients of sleep states within the daily sleep period. Advances in signal analysis revealed that the level of slow‐wave activity in non‐rapid eye movement sleep electroencephalogram is high at the beginning of the 12‐light period and then declines. After sleep deprivation, the level of slow‐wave activity is enhanced. By scheduling recovery sleep to the animal's activity period, the conflict between the sleep–wake‐dependent and the circadian influence resulted in a two‐stage recovery pattern. These experiments provided the basis for the first version of the two‐process model. Sleep deprivation experiments in humans showed that the decline of slow‐wave activity during sleep is exponential. The two‐process model posits that a sleep–wake‐dependent homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C). At present, homeostatic and circadian facets of sleep regulation are being investigated at the synaptic level as well as in the transcriptome and proteome domains. The notion of sleep has been extended from a global phenomenon to local representations, while the master circadian pacemaker has been supplemented by multiple peripheral oscillators. The original interpretation that the emergence of sleep may be viewed as an escape from the rigid control imposed by the circadian pacemaker is still upheld.

Obstructive sleep apnea: transition from pathophysiology to an integrative disease model

Abstract: Obstructive sleep apnea (OSA) is characterised by recurring episodes of upper airway obstruction during sleep and the fundamental abnormality reflects the inability of the upper airway dilating muscles to withstand the negative forces generated within the upper airway during inspiration. Factors that result in narrowing of the oropharynx such as abnormal craniofacial anatomy, soft tissue accumulation in the neck, and rostral fluid shift in the recumbent position increase the collapsing forces within the airway. The counteracting forces of upper airway dilating muscles, especially the genioglossus, are negatively influenced by sleep onset, inadequacy of the genioglossus responsiveness, ventilatory instability, especially post arousal, and loop gain. OSA is frequently associated with comorbidities that include metabolic, cardiovascular, renal, pulmonary, and neuropsychiatric, and there is growing evidence of bidirectional relationships between OSA and comorbidity, especially for heart failure, metabolic syndrome, and stroke. A detailed understanding of the complex pathophysiology of OSA encourages the development of therapies targeted at pathophysiological endotypes and facilitates a move towards precision medicine as a potential alternative to continuous positive airway pressure therapy in selected patients.

Sleep, insomnia and mental health

Abstract: While sleep serves important regulatory functions for mental health, sleep disturbances, in particular insomnia, may favour a state of allostatic overload impairing brain neuroplasticity and stress immune pathways, hence contributing to mental disorders. In this framework, the aim of this work was to link current understanding about insomnia mechanisms with current knowledge about mental health dysregulatory mechanisms. The focus of the present work was on mood, anxiety, and psychotic disorders, which represent important challenges in clinical practice. Literature searches were conducted on clinical, neurobiological, and therapeutic implications for insomnia comorbid with these mental disorders. Given the complexity and heterogeneity of the existing literature, we ended up with a narrative review. Insomnia may play an important role as a risk factor, a comorbid condition and transdiagnostic symptom for many mental disorders including mood/anxiety disorders and schizophrenia. Insomnia may also play a role as a marker of disrupted neuroplasticity contributing to dysregulation of different neurobiological mechanisms involved in these different mental conditions. In this framework, insomnia treatment may not only foster normal sleep processes but also the stress system, neuroinflammation and brain plasticity. Insomnia treatment may play an important preventive and neuroprotective role with cognitive behavioural therapy for insomnia being the treatment with important new evidence of efficacy for insomnia, psychopathology, and indices of disrupted neuroplasticity. On the other hand, pharmacological pathways for insomnia treatment in these mental conditions are still not well defined. Therapeutic options acting on melatonergic systems and new therapeutic options acting on orexinergic systems may represents interesting pathways of interventions that may open new windows on insomnia treatment in mental disorders.

Adenosine, caffeine, and sleep–wake regulation: state of the science and perspectives

Abstract: For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. For ~100 years now, systematic research has been performed, first started by testing the effects of different dosages of caffeine on sleep and waking behaviour. About 70 years ago, adenosine itself entered the picture as a possible ligand of the receptors where caffeine hooks on as an antagonist to reduce sleepiness. Since the scientific demonstration that this is indeed the case, progress has been fast. Today, adenosine is widely accepted as an endogenous sleep‐regulatory substance. In this review, we discuss the current state of the science in model organisms and humans on the working mechanisms of adenosine and caffeine on sleep. We critically investigate the evidence for a direct involvement in sleep homeostatic mechanisms and whether the effects of caffeine on sleep differ between acute intake and chronic consumption. In addition, we review the more recent evidence that adenosine levels may also influence the functioning of the circadian clock and address the question of whether sleep homeostasis and the circadian clock may interact through adenosinergic signalling. In the final section, we discuss the perspectives of possible clinical applications of the accumulated knowledge over the last century that may improve sleep‐related disorders. We conclude our review by highlighting some open questions that need to be answered, to better understand how adenosine and caffeine exactly regulate and influence sleep.

Sleep health

Abstract: Objective: In the United States (US), the health and financial consequences of COVID-19 have dis- proportionately impacted women and minoritized racial-ethnic groups. Yet, few US studies have investigated financial hardship during the COVID-19 pandemic and sleep health disparities. Our objective was to investigate associations between financial hardship and sleep disturbances during the COVID-19 pandemic by gender and race and ethnicity in the United States. Methods: We used the nationally representative COVID-19 ′ s Unequal Racial Burden cross-sectional survey data collected among 5339 men and women from 12/2020 to 2/2021. Participants reported financial hardship (eg, debt, employment/work loss) since the pandemic began and completed the Patient-Reported Outcomes Management Information System Short Form 4a for sleep disturbances. Prevalence ratios (PRs) and 95% confidence intervals were estimated using adjusted, weighted Poisson regression with robust variance. Results: Most (71%) participants reported financial hardship. Prevalence of moderate to severe sleep disturbances was 20% overall, higher among women (23%), and highest among American Indian/Alaska Native (29%) and multiracial adults (28%). Associations between financial hardship and moderate to severe sleep disturbances (PR = 1.52 [95% confidence interval: 1.18, 1.94]) did not differ by gender but varied by race and ethnicity: associations were strongest among Black/African American (PR = 3.52 [1.99,6.23]) adults. Conclusions: Both financial hardship and sleep disturbances were prevalent, and their relationships were strongest among certain minoritized racial-ethnic groups, particularly Black/African American adults. Interventions that alleviate financial insecurity may reduce sleep health disparities.

Sleep symptoms are essential features of long‐COVID – Comparing healthy controls with COVID‐19 cases of different severity in the international COVID sleep study (ICOSS‐II)

Abstract: Many people report suffering from post‐acute sequelae of COVID‐19 or “long‐COVID”, but there are still open questions on what actually constitutes long‐COVID and how prevalent it is. The current definition of post‐acute sequelae of COVID‐19 is based on voting using the Delphi‐method by the WHO post‐COVID‐19 working group. It emphasizes long‐lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post‐acute sequelae of COVID‐19. In this international survey study consisting of 13,628 subjects aged 18–99 years from 16 countries of Asia, Europe, North America and South America (May–Dec 2021), we show that post‐acute sequelae of COVID‐19 symptoms were more prevalent amongst the more severe COVID‐19 cases, i.e. those requiring hospitalisation for COVID‐19. We also found that long‐lasting sleep symptoms are at the core of post‐acute sequelae of COVID‐19 and associate with the COVID‐19 severity when COVID‐19 cases are compared with COVID‐negative cases. Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long‐lasting symptoms after hospitalisation for COVID‐19. Understanding the importance of sleep‐related symptoms in post‐acute sequelae of COVID‐19 has a clinical relevance when diagnosing and treating long‐COVID.

Worry about COVID‐19 as a predictor of future insomnia

Abstract: The coronavirus disease 2019 (COVID‐19) pandemic resulted in significant increases in insomnia, with up to 60% of people reporting increased insomnia. However, it is unclear whether exposure to risk factors for the virus or worries about COVID‐19 are more strongly associated with insomnia. Using a three‐part survey over the course of the first 6 months of the pandemic, we evaluated associations between COVID‐19 exposures, COVID‐19 worries, and insomnia. We hypothesised that COVID‐19‐related worries and exposure to risk of COVID‐19 would predict increases in insomnia. Participants (N = 3,560) completed a survey at three time‐points indicating their exposures to COVID‐19 risk factors, COVID‐19‐related worries, and insomnia. COVID‐19 worry variables were consistently associated with greater insomnia severity, whereas COVID‐19 exposure variables were not. COVID‐19 worries decreased significantly over time, and there were significant interactions between change in COVID‐19 worries and change in insomnia severity over time. Individuals who experienced increases in COVID‐19 worries also experienced increases in insomnia severity. Changes in worry during the COVID‐19 pandemic were associated with changes in insomnia; worries about COVID‐19 were a more consistent predictor of insomnia than COVID‐19 exposures. Evidence‐based treatments targeting virus‐related worries may improve insomnia during this and future calamities.

The multidimensionality of sleep in population‐based samples: a narrative review

Abstract: The identification of optimal sleep duration recommendations for the general population has long been an important goal on the public health agenda, as both short and long sleep duration have been linked to unfavourable health outcomes. Yet, sleep is more than duration alone and can be described across multiple domains, such as timing, regularity, satisfaction, alertness, and efficiency. We reviewed observational population‐based studies that examined differences in age, sex, and origin across multiple dimensions of sleep. Reviewed literature suggests an increasing prevalence of insomnia symptoms, shorter and less deep sleep in old age. Overall, women report poorer sleep quality than men despite objective measures revealing shorter and more fragmented sleep in men. Minorities generally have poorer quantity and quality of sleep, but multi‐ethnic studies have reported mixed results regarding the subjective experience of sleep. In sum, effects of age, sex and origin differ across sleep dimensions, thereby suggesting that the multidimensionality of sleep and how these different aspects interact should be studied across individuals. Studies should include both self‐reported measures and objective assessments in diverse population‐based samples, as both aspects are important to understand sleep health in the general population. Data‐driven descriptions could provide researchers and clinicians with insights into how well individuals are sleeping and offer concrete targets for promotion of sleep health across the population.

The circadian system, sleep, and the health/disease balance: a conceptual review

Abstract: The field of “circadian medicine” is a recent addition to chronobiology and sleep research efforts. It represents a logical step arising from the increasing insights into the circadian system and its interactions with life in urbanised societies; applying these insights to the health/disease balance at home and in the medical practice (outpatient) and clinic (inpatient). Despite its fast expansion and proliferating research efforts, circadian medicine lacks a formal framework to categorise the many observations describing interactions among the circadian system, sleep, and the health/disease balance. A good framework allows us to categorise observations and then assign them to one or more components with hypothesised interactions. Such assignments can lead to experiments that document causal (rather than correlational) relationships and move from describing observations to discovering mechanisms. This review details such a proposed formal framework for circadian medicine and will hopefully trigger discussion among our colleagues, so that the framework can be improved and expanded. As the basis of the framework for circadian medicine, we define “circadian health” and how it links to general health. We then define interactions among the circadian system, sleep, and the health/disease balance and put the framework into the context of the literature with examples from six domains of health/disease balance: fertility, cancer, immune system, mental health, cardiovascular, and metabolism.

What about dreams? State of the art and open questions

Abstract: Several studies have tried to identify the neurobiological bases of dream experiences, nevertheless some questions are still at the centre of the debate. Here, we summarise the main open issues concerning the neuroscientific study of dreaming. After overcoming the rapid eye movement (REM) ‐ non‐REM (NREM) sleep dichotomy, investigations have focussed on the specific functional or structural brain features predicting dream experience. On the one hand, some results underlined that specific trait‐like factors are associated with higher dream recall frequency. On the other hand, the electrophysiological milieu preceding dream report upon awakening is a crucial state‐like factor influencing the subsequent recall. Furthermore, dreaming is strictly related to waking experiences. Based on the continuity hypothesis, some findings reveal that dreaming could be modulated through visual, olfactory, or somatosensory stimulations. Also, it should be considered that the indirect access to dreaming remains an intrinsic limitation. Recent findings have revealed a greater concordance between parasomnia‐like events and dream contents. This means that parasomnia episodes might be an expression of the ongoing mental sleep activity and could represent a viable direct access to dream experience. Finally, we provide a picture on nightmares and emphasise the possible role of oneiric activity in psychotherapy. Overall, further efforts in dream science are needed (a) to develop a uniform protocol to study dream experience, (b) to introduce and integrate advanced techniques to better understand whether dreaming can be manipulated, (c) to clarify the relationship between parasomnia events and dreaming, and (d) to determine the clinical valence of dreams.

The Sleep Revolution project: the concept and objectives

Abstract: Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea–hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.

The orexin story, sleep and sleep disturbances

Abstract: The orexins, also known as hypocretins, are two neuropeptides (orexin A and B or hypocretin 1 and 2) produced by a few thousand neurons located in the lateral hypothalamus that were independently discovered by two research groups in 1998. Those two peptides bind two receptors (orexin/hypocretin receptor 1 and receptor 2) that are widely distributed in the brain and involved in the central physiological regulation of sleep and wakefulness, orexin receptor 2 having the major role in the maintenance of arousal. They are also implicated in a multiplicity of other functions, such as reward seeking, energy balance, autonomic regulation and emotional behaviours. The destruction of orexin neurons is responsible for the sleep disorder narcolepsy with cataplexy (type 1) in humans, and a defect of orexin signalling also causes a narcoleptic phenotype in several animal species. Orexin discovery is unprecedented in the history of sleep research, and pharmacological manipulations of orexin may have multiple therapeutic applications. Several orexin receptor antagonists were recently developed as new drugs for insomnia, and orexin agonists may be the next‐generation drugs for narcolepsy. Given the broad range of functions of the orexin system, these drugs might also be beneficial for treating various conditions other than sleep disorders in the near future.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid‐beta levels

Abstract: Obstructive sleep apnea is characterized by intermittent hypoxia and sleep disruption, leading to accelerated neurodegenerative changes and cognitive decline. Serum amyloid‐beta and tau proteins, which are markers for Alzheimer's disease, have been reported to increase in patients with obstructive sleep apnea. This study compared the serum levels of amyloid‐beta proteins and tau proteins in 46 cognitively normal obstructive sleep apnea patients and 30 healthy controls. Sleep parameters and severity of obstructive sleep apnea were determined using overnight polysomnography. Serum levels of Aβ40, Aβ42, total tau and phosphorylated‐tau were determined by enzyme‐linked immunosorbent assay. Patients with obstructive sleep apnea had significantly higher median serum levels of Aβ40 (121.0 versus 78.3 pg ml–1), Aβ42 (105.6 versus 18.6 pg ml–1) and total tau (168.5 versus 10.9 pg ml–1) than controls. Serum levels of phosphorylated‐tau did not differ significantly between the two groups. Serum levels of amyloid and tau proteins correlated with parameters of nocturnal oxygen saturation. Rapid eye movement sleep was negatively correlated with total amyloid‐beta proteins. We conclude that serum levels of amyloid‐beta and total tau are higher in patients with obstructive sleep apnea and hypoxia as well as changes in sleep architecture associated with their increased levels. Patients with obstructive sleep apnea should be closely monitored for the signs of cognitive impairment. Obstructive sleep apnea is a modifiable risk factor, and its treatment may reverse neurodegenerative changes and prevent cognitive impairment.

Effects of the COVID‐19 pandemic on sleep quality in children and adolescents: A systematic review and meta‐analysis

Abstract: We synthesise the literature on the potential influence of the COVID‐19 pandemic on sleep quality in children and adolescents. The search identified studies that examined the relationship between sleep quality and disorders during the COVID‐19 pandemic. It began in May 2021 and has had two updates with the last in January 2022. The databases used were LILACS, PubMed, and EMBASE. Random effects models were performed to explore heterogeneity between studies. Data were presented as continuous variables (mean value and standard deviation) to perform a meta‐analysis. Twenty‐nine studies from 16 countries were identified: Nine had children and eight had adolescents. The overall quality of the studies ranged from high (27.6%) to medium (65.5%) and low (6.9%). Eight studies were eligible for meta‐analysis. There was an increase in sleep duration during the pandemic when compared with the previous period 0.33 (95%CI −0.07; 0.60) (p < 0.001) and late bedtime 0.78 (95%CI −0.33; 1.22) (p < 0.001). A trend toward reduced sleep efficiency was also detected 0.54 (95%CI −0.75; −0.33) p = 0.20. Parents’ reports of increased use of screen media/electronic devices were associated with worse sleep quality. The results suggest an influence of the pandemic on sleep characteristics such as increased sleep duration, late bedtimes, and poor sleep quality. These alterations were related to changes in family routines during this period.

Sleepwalking, sleep terrors, sexsomnia and other disorders of arousal: the old and the new

Abstract: Disorders of arousal (DOA) is an umbrella term initially covering classical sleepwalking, sleep terrors, and confusional arousals, and now including a wider spectrum of specialised forms of non rapid eye movement (non REM) parasomnias such as sexsomnia, sleep‐related eating disorder, and sleep‐related choking syndrome. Growing evidence has shown that DOA are not restricted to children but are also prevalent in adults (2%–4% of the adult population). While DOA run in family, genetics studies remain scarce and inconclusive. In addition to the risk of injury on themselves and others (including sexual assaults in sexsomnia), adults with DOA frequently suffer from excessive daytime sleepiness, pain, and altered quality of life. The widespread view of DOA as automatic and amnesiac behaviours has now been challenged by subjective (dream reports) and objective (dream‐enacting behaviours documented on video‐polysomnography) observations, suggesting that sleepwalkers are ‘dream walking’ during their episodes. Behavioural, experiential, cognitive, and brain (scalp electroencephalography [EEG], stereo‐EEG, high density‐EEG, functional brain imaging) data converge in showing a dissociated pattern during the episodes. This dissociated pattern resembles the new concept of local arousal with a wake‐like activation in motor and limbic regions and a preserved (or even increased) sleep intensity over a frontoparietal network. EEG and behavioural criteria supporting the DOA diagnosis with high sensitivity and specificity are now available. However, treatment is still based on controlling priming and precipitating factors, as well as on clinicians’ personal experience with sedative drugs. Placebo‐controlled trials are needed to improve patients’ treatment. DOA deserve more attention from sleep researchers and clinicians.

The association of co‐morbid insomnia and sleep apnea with prevalent cardiovascular disease and incident cardiovascular events

Abstract: Insomnia and obstructive sleep apnea commonly co‐occur (co‐morbid insomnia and sleep apnea), and their co‐occurrence has been associated with worse cardiometabolic and mental health. However, it remains unknown if people with co‐morbid insomnia and sleep apnea are at a heightened risk of incident cardiovascular events. This study used longitudinal data from the Sleep Heart Health Study (N = 5803) to investigate potential associations between co‐morbid insomnia and sleep apnea and cardiovascular disease prevalence at baseline and cardiovascular event incidence over ~11 years follow‐up. Insomnia was defined as self‐reported difficulties initiating and/or maintaining sleep AND daytime impairment. Obstructive sleep apnea was defined as an apnea–hypopnea index ≥ 15 events per hr sleep. Co‐morbid insomnia and sleep apnea was defined if both conditions were present. Data from 4160 participants were used for this analysis. The prevalence of no insomnia/obstructive sleep apnea, insomnia only, obstructive sleep apnea only and co‐morbid insomnia and sleep apnea was 53.2%, 3.1%, 39.9% and 1.9%, respectively. Co‐morbid insomnia and sleep apnea was associated with a 75% (odd ratios [95% confidence interval]; 1.75 [1.14, 2.67]) increase in likelihood of having cardiovascular disease at baseline after adjusting for pre‐specified confounders. In the unadjusted model, co‐morbid insomnia and sleep apnea was associated with a twofold increase (hazard ratio, 95% confidence interval: 2.00 [1.33, 2.99]) in risk of cardiovascular event incidence. However, after adjusting for pre‐specified covariates, co‐morbid insomnia and sleep apnea was not significantly associated with incident cardiovascular events (hazard ratio 1.38 [0.92, 2.07]). Comparable findings were obtained when an alternative definition of insomnia (difficulties initiating and/or maintaining sleep without daytime impairment) was used.

The role of sleep and dreams in long‐COVID

Abstract: Recent investigations show that many people affected by SARS‐CoV2 (COVID‐19) report persistent symptoms 2–3 months from the onset of the infection. Here, we report the Italian findings from the second International COVID‐19 Sleep Study survey, aiming to investigate sleep and dream alterations in participants with post‐acute symptoms, and identify the best determinants of these alterations among patients with long‐COVID. Data from 383 participants who have had COVID‐19 were collected through a web‐survey (May–November 2021). Descriptive analyses were performed to outline the sociodemographic characteristics of long‐COVID (N = 270, with at least two long‐lasting symptoms) and short‐COVID (N = 113, with none or one long‐lasting symptom) participants. They were then compared concerning sleep and dream measures. We performed multiple linear regressions considering as dependent variables sleep and dream parameters discriminating the long‐COVID group. Age, gender, work status, financial burden, COVID‐19 severity and the level of care were significantly different between long‐COVID and short‐COVID subjects. The long‐COVID group showed greater sleep alterations (sleep quality, daytime sleepiness, sleep inertia, naps, insomnia, sleep apnea, nightmares) compared with the short‐COVID group. We also found that the number of long‐COVID symptoms, psychological factors and age were the best explanatory variables of sleep and oneiric alterations. Our findings highlight that sleep alterations are part of the clinical presentation of the long‐COVID syndrome. Moreover, psychological status and the number of post‐acute symptoms should be considered as state‐like variables modulating the sleep problems in long‐COVID individuals. Finally, according to previous investigations, oneiric alterations are confirmed as a reliable mental health index.

Two years after lockdown: Longitudinal trajectories of sleep disturbances and mental health over the COVID‐19 pandemic, and the effects of age, gender and chronotype

Abstract: Since the first lockdown of Spring 2020, the COVID‐19 contagion waves pervasively disrupted the sleep and mental health of the worldwide population. Notwithstanding the largest vaccination campaign in human history, the pandemic has continued to impact the everyday life of the general population for 2 years now. The present study provides the first evidence of the longitudinal trajectories of sleep disturbances and mental health throughout the pandemic in Italy, also describing the differential time course of age groups, genders and chronotypes. A total of 1062 Italians participated in a three‐time‐point longitudinal study covering two critical stages of the emergency (the first lockdown in April 2020 and the second partial lockdown in December 2020) and providing a long‐term overview 2 years after the pandemic outbreak (April 2022). We administered validated questionnaires to evaluate sleep quality/habits, insomnia, depression, stress and anxiety symptoms. Analyses showed a gradual improvement in sleep disturbances, depression and anxiety. Conversely, sleep duration progressively decreased, particularly in evening‐type and younger people. Participants reported substantial earlier bedtime and get‐up time. Stress levels increased during December 2020 and then stabilised. This effect was stronger in the population groups apparently more resilient during the first lockdown (older people, men and morning‐types). Our results describe a promising scenario 2 years after the pandemic onset. However, the improvements were relatively small, the perceived stress increased, and the re‐establishment of pre‐existing social/working dynamics led to general sleep curtailment. Further long‐term monitoring is required to claim the end of the COVID‐19 emergency on Italians' sleep and mental health.

Rise and shine: The use of polychromatic short‐wavelength‐enriched light to mitigate sleep inertia at night following awakening from slow‐wave sleep

Abstract: Sleep inertia is the brief period of performance impairment and reduced alertness experienced after waking, especially from slow‐wave sleep. We assessed the efficacy of polychromatic short‐wavelength‐enriched light to improve vigilant attention, alertness and mood immediately after waking from slow‐wave sleep at night. Twelve participants (six female, 23.3 ± 4.2 years) maintained an actigraphy‐confirmed sleep schedule of 8.5 hr for 5 nights, and 5 hr for 1 night prior to an overnight laboratory visit. In the laboratory, participants were awakened from slow‐wave sleep, and immediately exposed to either dim, red ambient light (control) or polychromatic short‐wavelength‐enriched light (light) for 1 hr in a randomized crossover design. They completed a 5‐min Psychomotor Vigilance Task, the Karolinska Sleepiness Scale, and Visual Analogue Scales of mood at 2, 17, 32 and 47 min after waking. Following this testing period, lights were turned off and participants returned to sleep. They were awakened from their subsequent slow‐wave sleep period and received the opposite condition. Compared with the control condition, participants exposed to light had fewer Psychomotor Vigilance Task lapses (χ2[1] = 5.285, p = 0.022), reported feeling more alert (Karolinska Sleepiness Scale: F1,77 = 4.955, p = 0.029; Visual Analogue Scalealert: F1,77 = 8.226, p = 0.005), and reported improved mood (Visual Analogue Scalecheerful: F1,77 = 8.615, p = 0.004). There was no significant difference in sleep‐onset latency between conditions following the testing period (t10 = 1.024, p = 0.330). Our results suggest that exposure to polychromatic short‐wavelength‐enriched light immediately after waking from slow‐wave sleep at night may help improve vigilant attention, subjective alertness, and mood. Future studies should explore the potential mechanisms of this countermeasure and its efficacy in real‐world environments.

50th anniversary of the ESRS in 2022-JSR special issue.

Abstract: This article addresses the clinical presentation, diagnosis, pathophysiology and management of narcolepsy type 1 and 2, with a focus on recent findings. A low level of hypocretin-1/orexin-A in the cerebrospinal fluid is sufficient to diagnose narcolepsy type 1, being a highly specific and sensitive biomarker, and the irreversible loss of hypocretin neurons is responsible for the main symptoms of the disease: sleepiness, cataplexy, sleep-related hallucinations and paralysis, and disrupted nocturnal sleep. The process responsible for the destruction of hypocretin neurons is highly suspected to be autoimmune, or dysimmune. Over the last two decades, remarkable progress has been made for the understanding of these mechanisms that were made possible with the development of new techniques. Conversely, narcolepsy type 2 is a less well-defined disorder, with a variable phenotype and evolution, and few reliable biomarkers discovered so far. There is a dearth of knowledge about this disorder, and its aetiology remains unclear and needs to be further explored. Treatment of narcolepsy is still nowadays only symptomatic, targeting sleepiness, cataplexy and disrupted nocturnal sleep. However, new psychostimulants have been recently developed, and the upcoming arrival of non-peptide hypocretin receptor-2 agonists should be a revolution in the management of this rare sleep disease, and maybe also for disorders beyond narcolepsy.

Correlates of excessive daytime sleepiness in obstructive sleep apnea: Results from the nationwide SESAR cohort including 34,684 patients

Abstract: Excessive daytime sleepiness (EDS) is a hallmark symptom in obstructive sleep apnea (OSA). It is commonly eliminated by obstructive sleep apnea therapy and constitutes a major treatment indication. This study aimed to identify determinants of excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS) scores in the large, representative national obstructive sleep apnea patient cohort of the Swedish Sleep Apnea Registry (SESAR, www.sesar.se). Data from 34,684 patients with obstructive sleep apnea recruited at 23 sites (33% females, mean age 55.7 ± 13.7 years, BMI 30.2 ± 6.3 kg/m2, AHI 29.1 ± 22.3, and ODI 24.9 ± 21.4 events/h) had a mean ESS score in the mild to moderate excessive daytime sleepiness range (9.7 ± 4.9). The proportion of patients with excessive daytime sleepiness was 41.4% in men and 44.6% in women. Independent predictors of excessive daytime sleepiness included gender, age, and hypoxic markers (high ODI and low mean saturation). Univariate and multivariate analyses were used to identify significant predictors for the ESS score and for excessive daytime sleepiness (ESS ≥10) amongst anthropometric factors, sleep apnea frequency (apnea‐hypopnea index (AHI)), markers of intermittent hypoxia (oxygen desaturation index (ODI), mean saturation (mSaO2)), as well as prevalent comorbidities. Depression was associated with higher ESS scores and hypertension/atrial fibrillation with lower scores. The oxygen desaturation index provided a stronger predictor of excessive daytime sleepiness than the apnea‐hypopnea index. The severity of obstructive sleep apnea, captured as the apnea‐hypopnea index, was only weakly associated with daytime sleepiness in this representative obstructive sleep apnea patient cohort. Age had different effects in men and women.The impact of obstructive sleep apnea in a wider patient related perspective needs to be determined after the inclusion of factors other than the apnea‐hypopnea index.

Circadian rest‐activity misalignment in critically ill medical intensive care unit patients

Abstract: Circadian alignment of rest–activity rhythms is an essential biological process that may be vulnerable to misalignment in critically ill patients. We evaluated circadian rest–activity rhythms in critically ill patients and their association with baseline (e.g. age) and clinical (e.g. mechanical ventilation status) variables, along with intensive care unit light–dark cycles. Using wrist actigraphy, we collected 48‐hr activity and light exposure data from critically ill patients in a tertiary care medical intensive care unit. We evaluated circadian rest–activity rhythms using COSINOR and non‐parametric circadian rhythm analysis models, and stratified these data across baseline and clinical variables. We used linear regression to evaluate the association of circadian rest–activity and light–dark exposure rhythms. In COSINOR and non‐parametric circadian rhythm analysis analyses, the 34 medical intensive care unit patients completing 48‐hr actigraphy recordings exhibited mean MESOR (mean activity levels of a fitted curve) and amplitudes of 0.50 ± 0.32 and 0.20 ± 0.19 movements per 30‐s epoch, with high interdaily variability. Patients who were older, mechanically ventilated, sedated, restrained and with higher organ failure scores tended to exhibit greater circadian rest–activity misalignment, with three of 34 (9%) patients exhibiting no circadian rhythmicity. Circadian light–dark exposure misalignment was observed as well and was associated with rest–activity misalignment (p = 0.03). Critically ill patients in our MICU experienced profound circadian rest–activity misalignment, with mostly weak or absent rhythms, along with circadian light–dark exposure misalignment. Potentially modifiable factors contributing to rest–activity misalignment (i.e. mechanical ventilation, restraints, low daytime light levels) highlight possible targets for future improvement efforts.

Sleep and epilepsy: A snapshot of knowledge and future research lines

Abstract: Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the “European school.” In particular, different aspects concerning the sleep–epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders.

Narcolepsy

Abstract: This article addresses the clinical presentation, diagnosis, pathophysiology and management of narcolepsy type 1 and 2, with a focus on recent findings. A low level of hypocretin‐1/orexin‐A in the cerebrospinal fluid is sufficient to diagnose narcolepsy type 1, being a highly specific and sensitive biomarker, and the irreversible loss of hypocretin neurons is responsible for the main symptoms of the disease: sleepiness, cataplexy, sleep‐related hallucinations and paralysis, and disrupted nocturnal sleep. The process responsible for the destruction of hypocretin neurons is highly suspected to be autoimmune, or dysimmune. Over the last two decades, remarkable progress has been made for the understanding of these mechanisms that were made possible with the development of new techniques. Conversely, narcolepsy type 2 is a less well‐defined disorder, with a variable phenotype and evolution, and few reliable biomarkers discovered so far. There is a dearth of knowledge about this disorder, and its aetiology remains unclear and needs to be further explored. Treatment of narcolepsy is still nowadays only symptomatic, targeting sleepiness, cataplexy and disrupted nocturnal sleep. However, new psychostimulants have been recently developed, and the upcoming arrival of non‐peptide hypocretin receptor‐2 agonists should be a revolution in the management of this rare sleep disease, and maybe also for disorders beyond narcolepsy.

Sleep apnea and the risk of dementia: A systematic review and meta‐analysis

Abstract: Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta‐analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26–1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16–1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30–1.84]). No statistically significant association was found for vascular dementia. One study reported a two‐fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45–2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

Rapid eye movement sleep behaviour disorder: Past, present, and future

Abstract: This manuscript presents an overview of REM sleep behaviour disorder (RBD) with a special focus on European contributions. After an introduction examining the history of the disorder, we address the pathophysiological and clinical aspects, as well as the diagnostic issues. Further, implications of RBD diagnosis and biomarkers are discussed. Contributions of European researchers to this field are highlighted.

Novel oxygen desaturation parameters are associated with cardiac troponin I: Data from the Akershus Sleep Apnea Project

Abstract: Novel diagnostic markers for obstructive sleep apnea beyond the apnea–hypopnea index (AHI) have been introduced. There are no studies on their association with markers of subclinical myocardial injury. We assessed the association between novel desaturation parameters and elevated cardiac troponin I and T. Participants with polysomnography (498) from the Akershus Sleep Apnea study were divided into normal and elevated biomarker groups based on sex‐specific concentration thresholds (cardiac troponin I: ≥4 ng/L for women, ≥6 ng/L for men; and cardiac troponin T: ≥7 ng/L for women, ≥8 ng/L for men). Severity of obstructive sleep apnea was evaluated with the AHI, oxygen desaturation index, total sleep time with oxygen saturation below 90% (T90), lowest oxygen saturation (Min SpO2%), and novel oxygen desaturation parameters: desaturation duration and desaturation severity. How the AHI and novel desaturation parameters predicted elevated cardiac troponin I and cardiac troponin T levels was assessed by the area under the curve (AUC). Based on multivariable‐adjusted linear regression, the AHI (β = 0.004, p = 0.012), desaturation duration (β = 0.007, p = 0.004), and desaturation severity (β = 0.147, p = 0.002) were associated with cardiac troponin I levels but not cardiac troponin T. T90 was associated with cardiac troponin I (β = 0.006, p = 0.009) and cardiac troponin T (β = 0.005, p = 0.007). The AUC for the AHI 0.592 (standard error 0.043) was not significantly different from the AUC of T90 (SD 0.640, p = 0.08), desaturation duration 0.609 (SD 0.044, p = 0.42) or desaturation severity 0.616 (SD 0.043, p = 0.26) in predicting myocardial injury as assessed by cardiac troponin I. Oxygen desaturation parameters and the AHI were associated with cardiac troponin I levels but not cardiac troponin T levels. Novel oxygen desaturation parameters did not improve the prediction of subclinical myocardial injury compared to the AHI.

Association of social jetlag and eating patterns with sleep quality and daytime sleepiness in Japanese high school students

Abstract: A high prevalence of excessive daytime sleepiness and poor sleep quality has been reported in adolescents, but the effects of social jetlag on sleep quality and daytime sleepiness are unclear. Therefore, we assessed the association of sleep and eating patterns with daytime sleepiness and sleep quality among a total of 756 Japanese high school students. Participants completed the Pittsburgh Sleep Quality Index to evaluate sleep quality, the Pediatric Daytime Sleepiness Scale to evaluate daytime sleepiness, and an 8‐day sleep diary. Data on average sleep duration, social jetlag, midsleep on free days sleep corrected, and the differences in the first and last meal timing between school days and non‐school days were obtained from participants' sleep diaries. The results reveal that social jetlag is associated with differences in the first meal timing between school days and non‐school days, and that social jetlag of more than 2 hr is associated with extremely poor sleep quality and excessive daytime sleepiness in Japanese high school students. Our findings suggest that reducing social jetlag to within a 2‐hr window is important to prevent poor sleep quality and excessive daytime sleepiness for this population.

Multimodal phenotypic labelling using drug‐induced sleep endoscopy, awake nasendoscopy and computational fluid dynamics for the prediction of mandibular advancement device treatment outcome: a prospective study

Abstract: Mandibular advancement device (MAD) treatment outcome for obstructive sleep apnea (OSA) is variable and patient dependent. A global, clinically applicable predictive model is lacking. Our aim was to combine characteristics obtained during drug‐induced sleep endoscopy (DISE), awake nasendoscopy, and computed tomography scan‐based computational fluid dynamic (CFD) measurements in one multifactorial model, to explain MAD treatment outcome. A total of 100 patients with OSA were prospectively recruited and treated with a MAD at fixed 75% protrusion. In all, 72 underwent CFD analysis, DISE, and awake nasendoscopy at baseline in a blinded fashion and completed a 3‐month follow‐up polysomnography with a MAD. Treatment response was defined as a reduction in the apnea–hypopnea index (AHI) of ≥50% and deterioration as an increase of ≥10% during MAD treatment. To cope with missing data, multiple imputation with predictive mean matching was used. Multivariate logistic regression, adjusting for body mass index and baseline AHI, was used to combine all potential predictor variables. The strongest impact concerning odds ratios (ORs) was present for complete concentric palatal collapse (CCCp) during DISE on deterioration (OR 28.88, 95% confidence interval [CI] 1.18–704.35; p = 0.0391), followed by a C‐shape versus an oval shape of the soft palate during wakefulness (OR 8.54, 95% CI 1.09–67.23; p = 0.0416) and tongue base collapse during DISE on response (OR 3.29, 95% CI 1.02–10.64; p = 0.0464). Both logistic regression models exhibited excellent and fair predictive accuracy. Our findings suggest DISE to be the most robust examination associated with MAD treatment outcome, with tongue base collapse as a predictor for successful MAD treatment and CCCp as an adverse DISE phenotype.