A tendency toward evening chronotype associates with less healthy diet among preschoolers: cross-sectional findings from the DAGIS study.

Study Objectives: Evidence suggests that adolescents and adults with a later chronotype have poorer sleep habits and are more susceptible to unhealthy behaviors, but little is known about these associations in younger children. The objective of the study was to (1) identify and compare individual chronotype tendencies among preschool-aged children and (2) investigate associations of sleep dimensions and chronotype with diet. Methods: Participants were 636 3-6 years old (mean ±â€…SD age: 4.74 ±â€…0.89 years, 49% girls) preschoolers from the cross-sectional Increased Health and Well-Being in Preschoolers (DAGIS) study in Finland. Sleep duration, sleep variability (in duration and midpoint), social jetlag, and midsleep on weekends adjusted for sleep debt (MSWEadj) were measured with 7-day actigraphy. Morning, intermediate, and evening chronotype tendencies were defined based on the lowest and highest 10th percentile cutoffs of MSWEadj. Food, energy, and macronutrient intake were assessed from 3-day records. Associations between sleep dimensions and diet were assessed with regression models. Results: MSWEadj was 1:13 ±â€…14 minutes for morning (n = 64), 2:25 ±â€…28 minutes for intermediate (n = 560), and 3:38 ±â€…15 minutes for evening (n = 64) chronotype tendency. Children with an evening chronotype tendency had greater social jetlag and sleep variability. Having an evening chronotype tendency was associated with higher added sugar, higher sugary food consumption, and lower vegetable consumption compared to intermediate tendency types. A later chronotype (MSWEadj) was associated with higher sugary food consumption, as well as lower vegetable and fiber intake. Sleep duration, social jetlag, and sleep variability were not associated with diet. Conclusions: Several less healthy sleep and diet behaviors were observed among children with later chronotypes. Future public health interventions aimed towards children would benefit from taking into account chronotype.

Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: Preliminary evidence.

OBJECTIVE/BACKGROUND: Idiopathic/isolated REM sleep behavior disorder (iRBD) is widely regarded as an early sign of neurodegeneration leading to synucleinopathies. While circadian rhythm alterations in iRBD have been preliminarily demonstrated, evidence on melatonin secretion patterns in this clinical condition is limited. To address this knowledge gap, this exploratory study aimed to integrate salivary melatonin measurement with actigraphic monitoring in individuals with iRBD and age-matched healthy controls (HC) under real-life conditions. METHODS: Participants diagnosed with iRBD and HC underwent clinical evaluation and wore an actigraph for seven days and nights. Salivary melatonin concentrations were measured at five time points during the last night of recording. Comparative analyses were conducted on clinical data, actigraphic parameters, and melatonin levels between the two groups. RESULTS: iRBD participants (n = 18) showed greater motor (p < 0.01) and non-motor symptoms (p < 0.001), alongside disruptions in circadian sleep-wake rhythm compared to HC (n = 10). Specifically, actigraphy revealed a delayed central phase measurement (p < 0.05), reduced activity during the most active hours (p < 0.001), and decreased relative amplitude (p < 0.05). Total salivary melatonin concentration was significantly lower in iRBD (p < 0.05), with a slight but non-significant phase delay in dim light melatonin onset. CONCLUSIONS: This exploratory study highlights a dysregulation of circadian sleep-wake rhythm coupled with reduced melatonin secretion in iRBD. Future research could add to these preliminary findings to evaluate novel treatment approaches to regulate the sleep-wake cycle and elucidate the implications of circadian dysregulation in the conversion from iRBD to neurodegeneration.

Assessment of cognitive function and sleep-wake rhythms in community-dwelling older adults.

Disruption of the circadian rhythm and sleep-wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60 years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r = - 0.276, p = 0.013, TE: r = 0.311, p = 0.005, PEN: r = 0.241, p = 0.032, NPE: r = 0.250, p = 0.025, DMS: r = 0.235, p = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD, revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: ß = - 0.322, p = 0.004; sleep timing SD: ß = - 0.250, p = 0.022). Assessment of sleep-wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population.

Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report.

The author recently observed a case involving a 12-year-old sighted girl who exhibited symptoms typical of non-24-hour sleep-wake rhythm disorder (N24SWD). This disorder, more commonly found in blind individuals, presents a unique challenge when diagnosed in those with vision. Several interventions can be attempted, ranging from behavioral adjustments to light therapy. Although melatonin has been noted for its effectiveness in realigning the patient's sleep-wake cycle, the use of ramelteon, a melatonin receptor agonist, has seldom been reported in managing N24SWD. However, this case illuminates the potential of ramelteon as another therapeutic option for sighted individuals with N24SWD. Further study is suggested to determine the potential of ramelteon in managing this disorder among sighted individuals of varying age groups. CITATION: Huang C-H. Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report. J Clin Sleep Med. 2024;20(6):995-997.

Registry and survey of circadian rhythm sleep-wake disorder patients.

Objective: Circadian Sleep Disorders Network has created a registry of circadian rhythm sleep-wake disorder (CRSWD) patients, and a survey of their experiences. The purpose of the registry is to provide volunteers willing to participate in research; the purpose of the survey is to fill some of the knowledge gaps on these disorders, including information on subjective patient experience and the efficacy and durability of treatments.Researchers are invited to contact Circadian Sleep Disorders Network for permission to use the registry to find potential research participants, and to further analyze the survey data. Patients: Over 1627 patients have participated; 1298 have completed the entire survey. Here we present results based on the 479 clinically diagnosed CRSWD patients. Methods: The survey covers a variety of topics relating to CRSWDs, including diagnosis, comorbidities, treatments, and work/educational accommodations. Conclusions: Results of this survey diverged from much of the literature. More than half the participants reported tiredness even when sleeping on their preferred schedule. While depression may cause sleep problems, our data suggests that sleep/circadian problems often precede depression.There were more people suffering from sighted non-24-hour sleep-wake rhythm disorder than some of the literature would lead us to expect.Current treatments did not appear to be helpful to a large percentage of our participants. Most of them did not find light therapy helpful and nearly all participants who tried phase-delay chronotherapy reported at best only short-term improvement. A sizable proportion of people who tried phase-delay chronotherapy subsequently developed non-24-hour sleep-wake rhythm disorder.

Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease.

Sleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk of disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted sleep and Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, and several orexin receptor antagonists (ORAs) are approved for the treatment of insomnia in adults. Dysregulation of the orexin system occurs in aging and AD, positioning ORAs as advantageous for these populations. Indeed, several clinical studies indicate that ORAs are efficacious hypnotics in older persons and dementia patients and, as in adults, are generally well tolerated. ORAs are likely to be more effective when administered early in sleep/wake dysregulation to reestablish good sleep/wake-related behaviors and reduce the accumulation of dementia-associated proteinopathic substrates. Improving sleep in aging and dementia represents a tremendous opportunity to benefit patients, caregivers, and health systems.

Images: Irregular sleep-wake rhythm disorder in transgender individuals.

Growing evidence suggests that transgender individuals face a significant health disparity and are particularly vulnerable to sleep disorders. We present two patients who developed irregular sleep-wake rhythm disorder after gender reassignment and hormone replacement therapy. The growing interest in transgender health warrants further evaluation of the effects and frequency of all sleep disorders in this population. Efforts to address sleep disorders should consider assessing sleep disturbance in terms of sleep/wake patterns and schedules. CITATION: Kokash A, Vendrame M. Images: irregular sleep-wake rhythm disorder in transgender individuals. J Clin Sleep Med. 2023;19(11):1981-1984.

Problems in the Development of the Sleep-Wake Rhythm Influence Neurodevelopmental Disorders in Children.

Development of the sleep-wake rhythm has a significant effect on the physical and mental development of children. The sleep-wake rhythm is controlled by aminergic neurons in the brainstem's ascending reticular activating system, which is associated with synaptogenesis and the promotion of brain development. The sleep-wake rhythm develops rapidly within the first year after birth. At 3-4 months of age, the framework of the circadian rhythm is established. The objective of the present review is to assess a hypothesis concerning problems in the development of the sleep-wake rhythm and their effect on neurodevelopmental disorders. Autism spectrum disorder is characterised by a delay in the development of sleep rhythms at 3-4 months of age and also insomnia and night-time awakenings, as supported by several reports. Melatonin may shorten the sleep latency in ASD. Rett syndrome sufferers kept awake during the daytime were analysed by the Sleep-wake Rhythm Investigation Support System (SWRISS) (IAC, Inc., (Tokyo, Japan)), and the cause was found to be the dysfunction of aminergic neurons. Children and adolescents with attention deficit hyperactivity disorder show sleep problems such as resistance to bedtime, difficulty falling asleep, sleep apnoea, and restless legs syndrome. Sleep deprivation syndrome in schoolchildren is deeply influenced by Internet use, games, and smartphones, and this syndrome affects emotion, learning, concentration, and executive functioning. Sleep disorders in adults are strongly considered to affect not only the physiological/autonomic nervous system but also neurocognitive/psychiatric symptoms. Even adults cannot avoid serious problems, much less children, and the impact of sleep problems is considerably greater in adults. Paediatricians and nurses should be aware of the significance, from birth, of sleep development and sleep hygiene education for carers and parents. This research was reviewed and approved by the ethical committee of the Segawa Memorial Neurological Clinic for Children (No. SMNCC23-02).

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review.

Background: The incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved. Methods: In this review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023. Results: Prolonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine's ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep-wake rhythm transitions. Conclusion: Our review revealed that the functional and structural abnormalities of sleep-wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.

Internal and external modulation factors of the orexin system (REVIEW).

Orexin-A and -B (identical to hypocretin-1 and -2) are neuropeptides synthesized in the lateral hypothalamus and perifornical area, and orexin neurons project their axon terminals broadly throughout the entire central nervous system (CNS). The activity of orexins is mediated by two specific G protein-coupled receptors (GPCRs), termed orexin type1 receptor (OX1R) and orexin type2 receptor (OX2R). The orexin system plays a relevant role in various physiological functions, including arousal, feeding, reward, and thermogenesis, and is key to human health. Orexin neurons receive various signals related to environmental, physiological, and emotional stimuli. Previous studies have reported that several neurotransmitters and neuromodulators influence the activation or inhibition of orexin neuron activity. In this review, we summarize the modulating factors of orexin neurons in the sleep/wake rhythm and feeding behavior, particularly in the context of the modulation of appetite, body fluids, and circadian signaling. We also describe the effects of life activity, behavior, and diet on the orexin system. Some studies have observed phenomena that have been verified in animal experiments, revealing the detailed mechanism and neural pathway, while their applications to humans is expected in future research.

Negative Impacts of Sleep-Wake Rhythm Disturbances on Attention in Young Adults.

Sleep-wake rhythm disturbances have a negative impact on attention. However, how it affects attention and whether the restoration of regular rhythms can restore attention are unclear. This study aims to explore the effects of sleep-wake rhythm disturbances on three subfunctions of attention (alertness, orientation, and executive control) and the restoration of regular rhythms on these functions. Twenty-one participants in the experimental group (who experienced sleep-wake rhythm disturbances for at least one month; aged 18-26) were required to sleep regularly following a sleep schedule, whereas 20 participants in the control group (who maintained regular sleep for at least three months; aged 19-22) received no manipulation of their sleep. All participants were assessed using the attention network test three times in six days. All of them wore spectrum activity monitors and kept sleep diaries every day. The results showed that the effects of alertness and executive control in the experimental group were significantly lower than those in the control group. After five days of regular sleep, the difference in the alertness effect between the two groups significantly decreased. These results suggested that under natural conditions, sleep-wake rhythm disturbances could negatively influence alertness and executive control, and a short period of restoring a regular rhythm has a recovery effect on alertness.

Delayed sleep-wake rhythm is associated with cognitive dysfunction, social dysfunction, and deteriorated quality of life in patients with major depressive disorder.

Background: The delayed sleep-wake phase is commonly observed in major depressive disorder (MDD) and thought to be associated with functional impairments. This study aimed to evaluate the relationship between the delayed sleep-wake phase, cognitive dysfunction, social dysfunction, and quality of life in patients with MDD. Methods: This cross-sectional design included 33 outpatients with MDD. Objective sleep-wake rhythm was assessed by actigraphy. Functional impairments were evaluated by the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J), World Health Organization Disability Assessment Schedule (WHO-DAS), and Euro QOL 5 dimensions (EQ5D). Results: Actigraphic assessment of the delayed sleep-wake phase (midpoint of sleep) was significantly correlated with the composite score of the BACS-J (r = -0.489, p = 0.010), WHO-DAS score (r = 0.466, p = 0.014), and EQ5D score (r = 0.472, p = 0.013). No significant correlation was found between the other actigraphic sleep parameters (sleep latency, total sleep time, and sleep efficiency) and functional impairments. Conclusion: Our study's results suggested that the delayed sleep-wake phase is associated with cognitive dysfunction, social dysfunction, and deteriorated quality of life in patients with MDD. Clinicians should pay attention to the sleep-wake rhythm in patients with MDD in clinical settings.

The two-process model of sleep regulation: Beginnings and outlook.

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.

Influence of shift work on rest-activity rhythms, sleep quality, and fatigue of female nurses.

Female nurses working rotating shifts must change their daily routines often, which affects their biological circadian rhythms and could cause sleep disorders and fatigue. The objective of this study was to compare the sleep-wake rhythms, sleep quality, and fatigue of female nurses working rotating shifts and fixed day shifts and to analyze the factors that influence their fatigue. Participants comprised a shift worker group of 101 nurses and a day worker group of 76 nurses. Following the collection of basic information of the nurses and their scores in the various constructs of the Pittsburg Sleep Quality Index (PSQI) and the Checklist Individual Strength (CIS) questionnaire, each nurse wore an actigraph for seven consecutive days to collect for analysis the sleep-wake rhythm parameter dichotomy index (I < O) and durations of continuous sleep and wake. Multivariable linear regression was then used to determine whether the influence of various variables on fatigue differed between the two groups. Results revealed that the sleep-wake rhythm parameter I < O of the day worker group was significantly higher than that of the shift worker group (t = 5.08, p < .001). The shift worker group exhibited significantly higher PSQI global scores (t = -2.00, p = .047), longer total sleep time (t = 2.07, p = .040), poorer habitual sleep efficiency (t = -3.06, p = .003), and greater use of sleeping medication (t = -2.90, p = .004) than did the day worker group. Multivariable linear regression was performed to analyze the important predictors of the CIS score in the two groups with body mass index, age, work experience, marital status, educational background, department of employment, shift type at the time of recruitment, sleep-wake rhythm parameter I < O, and quality of sleep as independent variables. Results indicated that in the shift worker group, the overall explanatory power (R2) of the multivariable linear regression model was 22.9% (F = 3.01, p = .003), and only the PSQI global score (ß = 0.33, p = .003) influenced the CIS score. In the day worker group, the various variables did not influence the CIS score in the multivariable linear regression model. Although the female nurses working rotating shifts spent more time in bed, their sleep-wake rhythms and sleep quality were poorer than those of the day worker group. Furthermore, the sleep quality of female nurses in the shift worker group had a significant impact on their fatigue. In other words, for female nurses who must work rotating shifts, sleep quality determines whether fatigue can be reduced. The shift-working nurses themselves should implement sleep management, such as avoiding disruptions to their sleep-wake rhythm and improving sleep quality, which should be effective strategies to reduce fatigue.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

STUDY OBJECTIVES: To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. METHODS: Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. RESULTS: No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. CONCLUSIONS: These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. CITATION: Emens JS, St Hilaire MA, Klerman EB, et al. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Wrist actigraphic approach in primary, secondary and tertiary care based on the principles of predictive, preventive and personalised (3P) medicine.

ABSTRACT: Sleep quality and duration as well as activity-rest-cycles at individual level are crucial for maintaining physical and mental health. Although several methods do exist to monitor these parameters, optimal approaches are still under consideration and technological development. Wrist actigraphy is a non-invasive electro-physical method validated in the field of chronobiology to record movements and to allow for monitoring human activity-rest-cycles. Based on the continuous recording of motor activity and light exposure, actigraphy provides valuable information about the quality and quantity of the sleep-wake rhythm and about the amount of motor activity at day and night that is highly relevant for predicting a potential disease and its targeted prevention as well as personalisation of medical services provided to individuals in suboptimal health conditions and patients. Being generally used in the field of sleep medicine, actigraphy demonstrates a great potential to be successfully implemented in primary, secondary and tertiary care, psychiatry, oncology, and intensive care, military and sports medicines as well as epidemiological monitoring of behavioural habits as well as well-being medical support, amongst others. PREDICTION OF DISEASE DEVELOPMENT AND INDIVIDUAL OUTCOMES: Activity-rest-cycles have been demonstrated to be an important predictor for many diseases including but not restricted to the development of metabolic, psychiatric and malignant pathologies. Moreover, activity-rest-cycles directly impact individual outcomes in corresponding patient cohorts. TARGETED PREVENTION: Data acquired by actigraphy are instrumental for the evidence-based targeted prevention by analysing individualised patient profiles including light exposure, sleep duration and quality, activity-rest-cycles, intensity and structure of motion pattern. PERSONALISED THERAPY: Wrist actigraphic approach is increasingly used in clinical care. Personalised measurements of sedation/agitation rhythms are useful for ICU patients, for evaluation of motor fatigue in oncologic patients, for an individual enhancement of performance in military and sport medicine. In the framework of personalised therapy intervention, patients can be encouraged to optimise their behavioural habits improving recovery and activity patterns. This opens excellent perspectives for the sleep-inducing medication and stimulants replacement as well as for increasing the role of participatory medicine by visualising and encouraging optimal behavioural patterns of the individual.

Sleep quality and COVID-19 outcomes: the evidence-based lessons in the framework of predictive, preventive and personalised (3P) medicine.

Sleep quality and duration play a pivotal role in maintaining physical and mental health. In turn, sleep shortage, deprivation and disorders are per evidence the risk factors and facilitators of a broad spectrum of disorders, amongst others including depression, stroke, chronic inflammation, cancers, immune defence insufficiency and individual predisposition to infection diseases with poor outcomes, for example, related to the COVID-19 pandemic. Keeping in mind that COVID-19-related global infection distribution is neither the first nor the last pandemic severely affecting societies around the globe to the costs of human lives accompanied with enormous economic burden, lessons by predictive, preventive and personalised (3P) medical approach are essential to learn and to follow being better prepared to defend against global pandemics. To this end, under extreme conditions such as the current COVID-19 pandemic, the reciprocal interrelationship between the sleep quality and individual outcomes becomes evident, namely, at the levels of disease predisposition, severe versus mild disease progression, development of disease complications, poor outcomes and related mortality for both - population and healthcare givers. The latter is the prominent example clearly demonstrating the causality of severe outcomes, when the long-lasting work overload and shift work rhythm evidently lead to the sleep shortage and/or deprivation that in turn causes immune response insufficiency and strong predisposition to the acute infection with complications. This article highlights and provides an in-depth analysis of the concerted risk factors related to the sleep disturbances under the COVID-19 pandemic followed by the evidence-based recommendations in the framework of predictive, preventive and personalised medical approach.

Treatment of a patient with a circadian sleep-wake disorder using a combination of melatonin and metoprolol.

CITATION: Circadian rhythm sleep-wake disorders result from the lack of synchronization between endogenous circadian rhythms and daily environmental or behavioral cycles. Current treatment of circadian rhythm sleep-wake disorders relies on strengthening normal zeitgebers, or temporal cues, through the combination of strict behavioral modification, controlled light exposure, and supplemental melatonin or melatonin receptor agonists. These therapies can be difficult to maintain and are supported with only limited clinical outcome data. The effectiveness of exogenous melatonin, in particular, may be reduced by the patient's continued production of endogenous melatonin with a temporal pattern that is not conducive to the desired sleep schedule. Here we describe the case of a single, sighted patient with a circadian rhythm sleep-wake disorder who benefited from the combined use of a beta blocker to suppress endogenous melatonin secretion along with the timed administration of exogenous melatonin. We suggest that the positive results obtained justify further study of this mechanism-guided approach. CITATION: Gehrman PR, Anafi RC. Treatment of a patient with a circadian sleep-wake disorder using a combination of melatonin and metoprolol. J Clin Sleep Med. 2021;17(10):2121-2124.

Evaluation of SAMP8 Mice as a Model for Sleep-Wake and Rhythm Disturbances Associated with Alzheimer's Disease: Impact of Treatment with the Dual Orexin (Hypocretin) Receptor Antagonist Lemborexant.

BACKGROUND: Many patients with Alzheimer's disease (AD) display circadian rhythm and sleep-wake disturbances. However, few mouse AD models exhibit these disturbances. Lemborexant, a dual orexin receptor antagonist, is under development for treating circadian rhythm disorders in dementia. OBJECTIVE: Evaluation of senescence-accelerated mouse prone-8 (SAMP8) mice as a model for sleep-wake and rhythm disturbances in AD and the effect of lemborexant by assessing sleep-wake/diurnal rhythm behavior. METHODS: SAMP8 and control senescence-accelerated mouse resistant-1 (SAMR1) mice received vehicle or lemborexant at light onset; plasma lemborexant and diurnal cerebrospinal fluid (CSF) orexin concentrations were assessed. Sleep-wake behavior and running wheel activity were evaluated. RESULTS: Plasma lemborexant concentrations were similar between strains. The peak/nadir timing of CSF orexin concentrations were approximately opposite between strains. During lights-on, SAMP8 mice showed less non-rapid eye movement (non-REM) and REM sleep than SAMR1 mice. Lemborexant treatment normalized wakefulness/non-REM sleep in SAMP8 mice. During lights-off, lemborexant-treated SAMR1 mice showed increased non-REM sleep; lemborexant-treated SAMP8 mice displayed increased wakefulness. SAMP8 mice showed differences in electroencephalogram architecture versus SAMR1 mice. SAMP8 mice exhibited more running wheel activity during lights-on. Lemborexant treatment reduced activity during lights-on and increased activity in the latter half of lights-off, demonstrating a corrective effect on overall diurnal rhythm. Lemborexant delayed the acrophase of activity in both strains by approximately 1 hour. CONCLUSION: SAMP8 mice display several aspects of sleep-wake and rhythm disturbances in AD, notably mistimed activity. These findings provide some preclinical rationale for evaluating lemborexant in patients with AD who experience sleep-wake and rhythm disturbances.

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.