A randomized controlled trial of alpha phase-locked auditory stimulation to treat symptoms of sleep onset insomnia.

Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked to slow-wave sleep oscillations have been shown to augment deep sleep, but it is unknown whether a similar approach can be used to accelerate sleep onset. The present randomized controlled crossover trial enrolled adults with objectively verified sleep onset latencies (SOLs) greater than 30 min to test the effect of auditory stimuli delivered at specific phases of participants' alpha oscillations prior to sleep onset. During the intervention week, participants wore an electroencephalogram (EEG)-enabled headband that delivered acoustic pulses timed to arrive anti-phase with alpha for 30 min (Stimulation). During the Sham week, the headband silently recorded EEG. The primary outcome was SOL determined by blinded scoring of EEG records. For the 21 subjects included in the analyses, stimulation had a significant effect on SOL according to a linear mixed effects model (p = 0.0019), and weekly average SOL decreased by 10.5 ± 15.9 min (29.3 ± 44.4%). These data suggest that phase-locked acoustic stimulation can be a viable alternative to pharmaceuticals to accelerate sleep onset in individuals with prolonged sleep onset latencies. Trial Registration: This trial was first registered on clinicaltrials.gov on 24/02/2023 under the name Sounds Locked to ElectroEncephalogram Phase For the Acceleration of Sleep Onset Time (SLEEPFAST), and assigned registry number NCT05743114.

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Insomnia.

Sleep significantly impacts health. Insomnia, characterized by difficulty with sleep onset, maintenance, and subsequent daytime symptoms, is increasingly prevalent and increases the risk of other medical comorbidities. The pathophysiology involves hyperarousal during non-REM sleep and altered sleep homeostasis. The 3P model explains the development and persistence of insomnia. Assessment is primarily clinical and based on appropriate history while distinguishing from other sleep disorders. "Somnomics" suggests a personalized approach to management. Cognitive behavioral therapy for insomnia is the first-line treatment in addition to other nonpharmacological strategies. Medications are a secondary option with weak supporting evidence.

Comparison of the Protective Effects of Casein Hydrolysate Containing Tyr-Pro-Val-Glu-Pro-Phe and Casein on the Behaviors and Peripheral and Brain Functions in Mice with Chronic-Stress-Induced Anxiety and Insomnia.

Chronic stress is a major inducer of anxiety and insomnia. Milk casein has been studied for its stress-relieving effects. We previously prepared a casein hydrolysate (CP) rich in the sleep-enhancing peptide YPVEPF, and this study aims to systemically investigate the different protective effects of CP and casein on dysfunction and anxiety/insomnia behavior and its underlying mechanisms in chronically stressed mice. Behavioral results showed that CP ameliorated stress-induced insomnia and anxiety more effectively than milk casein, and this difference in amelioration was highly correlated with an increase in GABA, 5-HT, GABAA, 5-HT1A receptors, and BDNF and a decrease in IL-6 and NMDA receptors in stressed mice. Furthermore, CP restored these dysfunctions in the brain and colon by activating the HPA response, modulating the ERK/CREB-BDNF-TrκB signaling pathway, and alleviating inflammation. The abundant YPVEPF (1.20 ± 0.04%) and Tyr-based/Trp-containing peptides of CP may be the key reasons for its different effects compared to casein. Thus, this work revealed the main active structures of CP and provided a novel dietary intervention strategy for the prevention and treatment of chronic-stress-induced dysfunction and anxiety/insomnia behaviors.

Polysomnographic parameters associated with cognitive function in patients with major depression and insomnia.

OBJECTIVE: To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. METHOD: Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. RESULTS: Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. CONCLUSION: Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.

Contribution of dysfunctional sleep-related cognitions on insomnia severity: a network perspective.

STUDY OBJECTIVES: Various models of insomnia stress the role of cognitive components, such as dysfunctional sleep-related beliefs, in maintenance and exacerbation of insomnia. This study aimed to use network analysis to identify the particular beliefs that are central and have strong associations with insomnia severity. In addition, we aimed to use a relative importance network to map out predictive pathways between types of dysfunctional beliefs and insomnia severity. METHODS: This study was a retrospective study, with data collected from 219 patients with insomnia. Patients' responses to the Dysfunctional Beliefs about Sleep Scale-16 (DBAS-16) and Insomnia Severity Index (ISI) were collected. All network analyses were performed using R Studio to produce 3 networks: (1) DBAS-16 network, (2) DBAS-16 and ISI network, and (3) relative importance network containing DBAS-16 subscales and ISI. RESULTS: Beliefs reflecting overestimation of negative consequences of sleep (eg, "insomnia is ruining life"), loss of ability (eg, "worry about losing abilities to sleep"), and unpredictability (eg, "can't predict sleep quality") were identified as most central and strongly associated with insomnia severity. Worry/helplessness about insomnia had the largest predictive value on insomnia severity, and also acted as a mediator between other subscales and insomnia severity. CONCLUSIONS: The results of our study suggest that overestimation of negative consequences, loss of ability, and unpredictability are key beliefs that exacerbate and maintain insomnia, thus supporting existing cognitive models of insomnia. CITATION: Cha EJ, Hong S, Kim S, Chung S, Jeon HJ. Contribution of dysfunctional sleep-related cognitions on insomnia severity: a network perspective. J Clin Sleep Med. 2024;20(5):743-751.

Is the insomnia phenotype the common denominator in LUTS during transition periods? An expert NOPIA research group review.

AIMS: As people age, sleep stages and characteristics transition over time, but sleep deficits can profoundly impact health and cognitive functioning. Chronic sleep deprivation is linked to impaired attention and productivity, weakened immunity, increased risk of cardiovascular disease, obesity, and mental health disorders. Insomnia, obstructive sleep apnea syndrome, hormonal changes, nocturia, neurological disorders, and life events interfere with sleep patterns and some are linked to lower urinary tract symptoms (LUTS). This NOPIA symposium on Lifelong LUTS aimed to analyze the literature on associations between sleep and LUTS, generate ideas for future research, and explore whether there is support for the concept of lifelong LUTS in relation to changes in sleep throughout the lifespan. METHODS: An international panel of experts took part in an online meeting addressing the role of lifelong LUTS in relationship to sleep and the brain organized by the NOPIA research group. The manuscript summarizes existing literature, hypotheses, future research ideas, and clinical recommendations. RESULTS: Insomnia, sleep fragmentation, hyperarousal, and sensory processing disorders emerged as potential factors in the relationship between sleep and LUTS. Insomnia is often a persistent factor and may have been the initial symptom; however, it is often unrecognized and/or unaddressed in healthcare settings. By recognizing insomnia as a primary driver of various health issues, including nocturia, transitional care aims to address root causes and underlying problems earlier to initiate appropriate treatment. CONCLUSIONS: A multidisciplinary approach with collaboration between healthcare professionals from various disciplines, such as urology, sleep medicine, gynecology, pediatrics, and geriatrics, is needed and should include validated measurements such as the insomnia severity index and sleep and voiding diaries. Ensuring ongoing follow-up and monitoring through transitional care is crucial for individuals with persistent sleep problems and LUTS, allowing issues that arise or fluctuate over the lifespan to be addressed.

The association between sleep parameters and sarcopenia in Japanese community-dwelling older adults.

PURPOSE: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. METHODS: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. RESULTS: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. CONCLUSIONS: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

Sleep as a protective factor of children's executive functions: A study during COVID-19 confinement.

Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children's sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental intervention, we tested whether worsened children's sleep affects executive functions outcomes 6 months downstream. We hypothesized that acutely increased night awakenings and sleep latency relate to reduced later executive functions. With an online survey during the acute confinement phase we analyzed sleep behavior in 45 children (36-72 months). A first survey referred to the (retrospective) time before and (acute) situation during confinement, and a follow-up survey assessed executive functions 6 months later (6 months retrospectively). Indeed, acutely increased nighttime awakenings related to reduced inhibition at FOLLOW-UP. Associations were specific to the confinement-induced sleep-change and not the sleep behavior before confinement. These findings highlight that specifically acute changes of children's nighttime sleep during sensitive periods are associated with behavioral outcome consequences. This aligns with observations in animals that inducing poor sleep during developmental periods affects later brain function.

Temporal relations between peripheral and central arousals in good and poor sleepers.

Good sleepers and patients with insomnia symptoms (poor sleepers) were tracked with two measures of arousal; conventional polysomnography (PSG) for electroencephalogram (EEG) assessed cortical arousals, and a peripheral arterial tonometry device was used for the detection of peripheral nervous system (PNS) arousals associated with vasoconstrictions. The relationship between central (cortical) and peripheral (autonomic) arousals was examined by evaluating their close temporal dynamics. Cortical arousals almost invariably were preceded and followed by peripheral activations, while large peripheral autonomic arousals were followed by cortical arousals only half of the time. The temporal contiguity of these two types of arousals was altered in poor sleepers, and poor sleepers displayed a higher number of cortical and peripheral arousals compared with good sleepers. Given the difference in the number of peripheral autonomic arousals between good and poor sleepers, an evaluation of such arousals could become a means of physiologically distinguishing poor sleepers.

Etiologies of insomnia in Parkinson's disease - Lessons from human studies and animal models.

Sleep disorders are integral to Parkinson's disease (PD). Insomnia, an inability to maintain stable sleep, affects most patients and is widely rated as one of the most debilitating facets of this disease. PD insomnia is often perceived as a multifactorial entity - a consequence of several of the disease symptoms, comorbidities and therapeutic strategies. Yet, this view evolved against a backdrop of a relative scarcity of works trying to directly dissect the underlying neural correlates and mechanisms in animal models. The last years have seen the emergence of a wealth of new evidence regarding the neural underpinnings of insomnia in PD. Here, we review early and recent reports from patients and animal models evaluating the etiology of PD insomnia. We start by outlining the phenomenology of PD insomnia and continue to analyze the evidence supporting insomnia as emanating from four distinct subdivisions of etiologies - the symptoms and comorbidities of the disease, the medical therapy, the degeneration of non-dopaminergic cell groups and subsequent alterations in circadian rhythms, and the degeneration of dopaminergic neurons in the brainstem and its resulting effect on the basal ganglia. Finally, we review emerging neuromodulation-based therapeutic avenues for PD insomnia.

Is there any relation between arterial stiffness and insomnia? A challenging question.

PURPOSE: Insomnia is a common sleep disorder which has high comorbidity with a number of cardiovascular diseases (CVD). As a possible risk factor for the CVDs, arterial stiffness may be assessed non-invasively by pulse wave velocity (PWV) and augmentation index (AI). The aim of this study was to evaluate any relation between insomnia and arterial stiffness. METHODS: Patients with insomnia were included in the study after the exclusion of other sleep disorders by polysomnography. Sleep quality and the degree of insomnia symptoms were evaluated by the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI), respectively. PWV and AI were assessed by Mobil-O-Graph arteriograph system. RESULTS: Consecutive patients with insomnia (n = 72, 56 women, mean age 55.8 ± 9.1 years) were included. Patients were grouped as those with severe ISI scores (22-28) and those with mild to moderate ISI scores (8-21). Despite no significant difference in characteristics and clinical data, patients with severe ISI scores had significantly higher total PSQI scores and NREM-2 with significantly lower REM duration. They also had significantly higher systolic blood pressure, mean blood pressure, pulse pressure, PWV, and AI compared to patients with mild and moderate ISI scores. Correlation analysis revealed that PWV and AI were significantly correlated with the ISI score and PSQI score. CONCLUSION: There is a close relation between arterial stiffness and insomnia suggesting a risk for CVD in patients with insomnia.

Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns).

OBJECTIVES: Knowledge on the course of symptoms patients with ovarian cancer experience is limited. We documented the prevalence and trajectories of symptoms after first-line chemotherapy using the Measure of Ovarian Symptoms and Treatment concerns (MOST). METHODS: A total of 726 patients who received platinum-based chemotherapy for ovarian cancer were asked to complete the MOST every 3 months, beginning 6 months post-diagnosis and continuing for up to 4 years. We used descriptive statistics to examine temporal changes in MOST-S26 index scores for disease or treatment-related (MOST-DorT), neurotoxicity (MOST-NTx), abdominal (MOST-Abdo), and psychological (MOST-Psych) symptoms, and wellbeing (MOST-Wellbeing) and selected individual symptoms. We used group-based trajectory models to identify groups with persistently poor symptoms. RESULTS: The median MOST-Abdo, MOST-DorT and MOST-Wellbeing score were worst at chemotherapy-end but improved and stabilised by 1, 3 and 12 months after treatment, respectively. The median MOST-NTx score peaked at 1 month after treatment before improving, while the median MOST-Psych score did not change substantially over time. Long-term moderate-to-severe fatigue (32%), trouble sleeping (31%), sore hands and feet (21%), pins and needles (20%) and anxiety (18%) were common. Trajectory models revealed groups of patients with persistent symptoms had MOST-DorT scores above 30 and MOST-NTx scores above 40 at treatment-end. CONCLUSIONS: Although many patients report improvements in symptoms by 3 months after first-line chemotherapy for ovarian cancer, patients who score > 30/100 on MOST-S26-DorT or > 40/100 on MOST-S26-NTx at the end of chemotherapy are likely to have persistent symptoms. The MOST could triage this at-risk subset for early intervention.

Application of Chaihu-Guizhi-Longgu-Muli decoction combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum ß-endorphin (ß-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P<0.001). The estrogen levels, ß-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P<0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P<0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

Insomnia and sleep deprivation in patients with epilepsy: issues about the pathophysiological interaction between them / Insônia e privação de sono em pacientes com epilepsia: questões sobre a interação fisiopatológica entre eles

There is a known relationship between seizures and sleep deprivation that increases epileptiform abnormalities and slow waves expressed in the EEG, but chronic insomnia, greater in patients with epilepsy (PWEs) than in healthy control, supposedly has a different mechanism linked to a hyperarousability state with increased rapid EEG activity and associated "restless REM". Therefore, there is a complex interaction at various levels between insomnia and epilepsy that may play a role in seizure presentation. The recognized interconnection between mood and anxiety disorders and insomnia should also advise special care in the management of psychiatric comorbidities in PWEs. This article raises questions related to the interaction between the brain basis of insomnia and epilepsy and the triggers of seizures, particularly sleep deprivation.

Há uma relação conhecida entre crises epilépticas e privação de sono que aumenta as anormalidades epileptiformes e as ondas lentas expressas no EEG, mas a insônia crônica, maior em pacientes com epilepsia (PCE) do que no controle saudável, supostamente tem um mecanismo diferente ligado a um estado de hiperexcitabilidade com aumento da atividade rápida do EEG e associado "REM inquieto". Consequentemente, existe uma complexa interação em vários níveis entre a insônia e a epilepsia que pode desempenhar um papel na apresentação das crises. A reconhecida interligação entre transtornos de humor e ansiedade com a insônia também deve aconselhar um cuidado especial no manejo das comorbidades psiquiátricas do PCE. Este artigo levanta questões relacionadas à interação entre a base cerebral da insônia e da epilepsia e os desencadeadores de crises epilépticas, principalmente a privação do sono.

Examining relationships between sleep posture, waking spinal symptoms and quality of sleep: A cross sectional study.

INTRODUCTION: Research with a focus on sleep posture has been conducted in association with sleep pathologies such as insomnia and positional obstructive sleep apnoea. Research examining the potential role sleep posture may have on waking spinal symptoms and quality of sleep is however limited. The aims of this research were to compare sleep posture and sleep quality in participants with and without waking spinal symptoms. METHODS: Fifty-three participants (36 female) were, based on symptoms, allocated to one of three groups; Control (n = 20, 16 female), Cervical (n = 13, 10 female) and Lumbar (n = 20, 10 female). Participants completed an online survey to collect general information and patient reported outcomes and were videoed over two consecutive nights to determine sleep posture using a validated classification system including intermediate sleep postures. RESULTS: Participants in the symptomatic groups also reported a lower sleep quality than the Control group. Compared to Control group participants, those in the Cervical group had more frequent posture changes (mean (SD); 18.3(6.5) versus 23.6(6.6)), spent more time in undesirable/provocative sleep postures (median IQR; 83.8(16.4,105.2) versus 185.1(118.0,251.8)) minutes and had more long periods of immobility in a provocative posture, (median IQR: 0.5(0.0,1.5) versus 2.0 (1.5,4.0)). There were no significant differences between the Control and Lumbar groups in the number of posture changes (18.3(6.5) versus 22.9(9.1)) or the time spent in provocative sleep postures (0.5(0.0,1.5) versus 1.5(1.5,3.4)) minutes. DISCUSSION: This is the first study using a validated objective measure of sleep posture to compare symptomatic and Control group participants sleeping in their home environment. In general, participants with waking spinal symptoms spent more time in provocative sleep postures, and experienced poorer sleep quality.

Persistence of sleep difficulties for over 16 years amongst 66,948 working-aged adults.

The objective was to investigate the persistence of sleep difficulties for over 16 years amongst a population of working age. In this prospective cohort study, a group-based trajectory analysis of repeated surveys amongst 66,948 employees in public sector (mean age 44.7 [SD 9.4] years, 80% women) was employed. The main outcome measure was sleep difficulties based on Jenkins Sleep Scale (JSS). Up to 70% of the respondents did not experience sleep difficulties whereas up to 4% reported high frequency of notable sleep difficulties through the entire 16-year follow-up. Heavy drinking predicted sleep difficulties (OR 2.3 95% CI 1.6 to 3.3) except for the respondents younger than 40 years. Smoking was associated with sleep difficulties amongst women younger than 40 years (OR 1.2, 95% CI 1.0 to 1.5). Obesity was associated with sleep difficulties amongst men (OR 1.9, 95% CI 1.4 to 2.7) and women (OR 1.2, 95% CI 1.1 to 1.3) of middle age and amongst women older than 50 (OR 1.5, 95% CI 1.2 to 1.8) years. Physical inactivity predicted sleep difficulties amongst older men (OR 1.3, 95% CI 1.1 to 1.6). In this working-age population, sleep difficulties showed a great persistence over time. In most of the groups, the level of sleep difficulties during the follow-up was almost solely dependent on the level of initial severity. Depending on sex and age, increasing sleep problems were sometimes associated with high alcohol consumption, smoking, obesity and physical inactivity, but the strength of these associations varied.

Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link.

Sleep disturbances, such as insomnia, obstructive sleep apnea, and daytime sleepiness, are common in people diagnosed with epilepsy. These disturbances can be attributed to nocturnal seizures, psychosocial factors, and/or the use of anti-epileptic drugs with sleep-modifying side effects. Epilepsy patients with poor sleep quality have intensified seizure frequency and disease progression compared to their well-rested counterparts. A better understanding of the complex relationship between sleep and epilepsy is needed, since approximately 20% of seizures and more than 90% of sudden unexpected deaths in epilepsy occur during sleep. Emerging studies suggest that neuroinflammation, (e.g., the CNS immune response characterized by the change in expression of inflammatory mediators and glial activation) may be a potential link between sleep deprivation and seizures. Here, we review the mechanisms by which sleep deprivation induces neuroinflammation and propose that neuroinflammation synergizes with seizure activity to worsen neurodegeneration in the epileptic brain. Additionally, we highlight the relevance of sleep interventions, often overlooked by physicians, to manage seizures, prevent epilepsy-related mortality, and improve quality of life.