Impact of sleep disturbances on outcomes in intensive care units.

BACKGROUND: Sleep deprivation is common in intensive care units (ICUs) and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients. OBJECTIVES: We hypothesized that sleep disturbances may be associated with poor outcomes in ICUs. METHODS: Post-hoc analysis pooling three observational studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in a group of patients admitted for acute respiratory failure while breathing spontaneously (n = 34), or under mechanical ventilation in patients with weaning difficulties (n = 45), or immediately after extubation (n = 52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes. RESULTS: Whereas deep sleep remained preserved in patients admitted for acute respiratory failure, it was markedly reduced under mechanical ventilation and after extubation (p < 0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p < 0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03). CONCLUSION: Complete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients.

Integrating the Memory Support Intervention into the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C): can improving memory for treatment in midlife and older adults improve patient outcomes? Study protocol for a randomized controlled trial.

BACKGROUND: Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. METHODS: Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. DISCUSSION: This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Cortical kappa opioid receptors integrate negative affect and sleep disturbance.

Sleep disruption and negative affect are attendant features of many psychiatric and neurological conditions that are often co-morbid including major depressive disorder, generalized anxiety disorder and chronic pain. Whether there is a causal relationship between negative affect and sleep disruption remains unclear. We therefore asked if mechanisms promoting negative affect can disrupt sleep and whether inhibition of pathological negative affect can normalize disrupted sleep. Signaling at the kappa opioid receptor (KOR) elicits dysphoria in humans and aversive conditioning in animals. We tested the possibility that (a) increased KOR signaling in the anterior cingulate cortex (ACC), a brain region associated with negative emotions, would be sufficient to promote both aversiveness and sleep disruption and (b) inhibition of KOR signaling would normalize pathological negative affect and sleep disruption induced by chronic pain. Chemogenetic Gi-mediated inhibition of KOR-expressing ACC neurons produced conditioned place aversion (CPA) as well as sleep fragmentation in naïve mice. CRISPR/Cas9 editing of ACC KOR normalized both the negative affect and sleep disruption elicited by pathological chronic pain while maintaining the physiologically critical sensory features of pain. These findings suggest therapeutic utility of KOR antagonists for treatment of disease conditions that are associated with both negative affect and sleep disturbances.

High Somatization Rates, Frequent Spontaneous Recovery, and a Lack of Organic Biomarkers in Post-Covid-19 Condition.

INTRODUCTION: Many patients report neuropsychiatric symptoms after SARS-CoV-2 infection. Data on prevalence of post-COVID-19 condition (PCC) vary due to the lack of specific diagnostic criteria, the report of unspecific symptoms, and reliable biomarkers. METHODS: PCC patients seen in a neurological outpatient department were followed for up to 18 months. Neurological examination, SARS-CoV-2 antibodies, Epstein-Barr virus antibodies, and cortisol levels as possible biomarkers, questionnaires to evaluate neuropsychiatric symptoms and somatization (Patient Health Questionnaires D [PHQ-D]), cognition deficits (Montreal Cognitive Assessment [MoCA]), sleep disorders (ISS, Epworth Sleepiness Scale [ESS]), and fatigue (FSS) were included. RESULTS: A total of 175 consecutive patients (78% females, median age 42 years) were seen between May 2021 and February 2023. Fatigue, subjective stress intolerance, and subjective cognitive deficits were the most common symptoms. Specific scores were positive for fatigue, insomnia, and sleepiness and were present in 95%, 62.1%, and 44.0%, respectively. Cognitive deficits were found in 2.3%. Signs of somatization were identified in 61%, who also had an average of two symptoms more than patients without somatization. Overall, 28% had a psychiatric disorder, including depression and anxiety. At the second visit (n = 92), fatigue (67.3%) and insomnia (45.5%) had decreased. At visit three (n = 43), symptom load had decreased in 76.8%; overall, 51.2% of patients were symptom-free. Biomarker testing did not confirm an anti-EBV response. SARS-CoV-2-specific immune reactions increased over time, and cortisol levels were within the physiological range. CONCLUSION: Despite high initial symptom load, 76.8% improved over time. The prevalence of somatization and psychiatric disorders was high. Our data do not confirm the role of previously suggested biomarkers in PCC patients.

Sleep correlates of behavior functioning in Cornelia de Lange syndrome.

Pathogenic variants in the cohesin genes, NIPBL and SMC1A, both cause Cornelia de Lange syndrome (CdLS), a rare genetic disorder associated with developmental delay and intellectual disability. This study aimed to compare sleep behaviors across individuals with CdLS caused by a variant in NIPBL or SMC1A, and identify relationships between sleep and behavior functioning. A total of 31 caregivers of individuals with a variant in NIPBL (N = 22) or SMC1A (N = 9) completed questionnaires regarding their child's sleep behaviors, behavior regulation, attention, and autistic features (repetitive behaviors and social communication difficulties) as part of the Coordination of Rare Diseases (CoRDS) registry. Findings showed a trend of increased behavior regulation difficulties and repetitive behaviors in the NIPBL compared to the SMC1A participants. Both groups presented with a similar degree of attention, social communication, and sleep challenges. In the whole sample, sleep disturbance was strongly correlated with more behavior regulation difficulties, a relationship that was more robust in the NIPBL sample. In brief, study results support our prior observations of greater behavior difficulties among those with a variant in NIPBL as compared to SMC1A. Preliminary findings point to unique associations between sleep and behavior regulation in the NIPBL group, suggesting sleep interventions may yield differential effects on behavior management across variants.

[Sleep in chronic neuropediatric diseases]. / Sueño en enfermedades neuropediátricas crónicas.

The prevalence of sleep disorders (SD) is notoriously increased in children with chronic neurological disease, with a negative bidirectional link that aggravates their symptomatology and has a negative impact on the quality of life of the child and their families. Identifying and recognizing this association is key for the child neurologist since the treatment of SD significantly improves daytime symptomatology in neurodevelopmental disorders, epilepsy, primary headaches, cerebral palsy and neuromuscular diseases.

La prevalencia de los trastornos del sueño (TS) se incrementa notoriamente en niños con enfermedad neurológica crónica, con un vínculo bidireccional negativo que agrava su sintomatología y repercute negativamente en la calidad de vida del niño y su familia. Identificar y reconocer dicha asociación es clave para el neuropediatra, ya que el tratamiento del TS mejora significativamente la sintomatología diurna de los trastornos del neurodesarrollo, epilepsia, cefaleas primarias, parálisis cerebral y enfermedades neuromusculares.

SPECT/CT imaging of poor sleep quality in people with epilepsy.

PURPOSE: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE). METHODS: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE. RESULTS: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups. CONCLUSION: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe.

Association between waist circumference and sleep disorder in the elderly: Based on the NHANES 2005-2018.

The existing data do not consistently support the link between elderly adults' waist circumferences and sleep disorders. This study aimed to evaluate whether waist circumference was connected with sleep disorder in the elderly. This cross-sectional study utilized data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) regarding waist circumference, sleep disorders, and confounding factors. Included in the study were participants older than 60 who completed sleep questionnaires and waist circumference measurements. Using a multivariate logistic regression model and subgroup analyses, the relationship between waist circumference and sleep disorder was evaluated. To explore the non-linear relationship, restricted cubic spline (RCS) with three knots coupled with a logistic regression model to assess the dose-response relationship between waist circumference (continuous variables) and sleep disorder. A total of 2,545 (Weighted 14,682,916.3) elderly participants with complete information were included in the analysis and 312 (Weighted 1,777,137.8) subjects met the definition of sleep disorder. Compared with participants without sleep disorder, those with sleep disorder had a higher waist circumference (100.80 cm vs. 108.96 cm, P< 0.001). The results of the multivariable adjusted logistic regression model suggested that those in quartiles 4 (≥ 75th percentile) for their waist circumference had higher odds of sleep disorder [adjusted odds ratio (AOR) = 2.75, 95% confidence interval (CI) = 1.66-4.54, P < 0.001] compared with those in quartile 1. The RCS result showed that the OR of sleep disorder and waist circumference displayed a linear relationship (P <0.001, Non-linear P = 0.642). Age and gender subgroup analysis revealed comparable relationships between waist circumference and sleep disorder among elderly individuals. Waist circumference was associated with sleep disorders in the elderly. There was a dose-response relationship between waist circumference and the likelihood of sleep disorder. Those with a larger waist circumference were more likely to have a sleep disorder than those with a smaller waist circumference.

Sleep Disorders.

AbstractThere are more than 90 recognized sleep disorders, many of which impair sleep and daytime function and adversely impact heath, well-being, and chronic disease risk. Unfortunately, many sleep disorders are undiagnosed or not managed effectively. This review describes how to identify, evaluate, and treat common sleep disorders.

Sleep disorders and Parkinson's disease: is there a right direction?

In the last years, the hypothesis of a close relationship between sleep disorders (SDs) and Parkinson's disease (PD) has significantly strengthened. Whether this association is causal has been also highlighted by recent evidence demonstrating a neurobiological link between SDs and PD. Thus, the question is not whether these two chronic conditions are mutually connected, but rather how and when this relationship is expressed. Supporting this, not all SDs manifest with the same temporal sequence in PD patients. Indeed, SDs can precede or occur concomitantly with the onset of the clinical manifestation of PD. This review discusses the existing literature, putting under a magnifying glass the timing of occurrence of SDs in PD-neurodegeneration. Based on this, here, we propose two possible directions for studying the SDs-PD relationship: the first direction, from SDs to PD, considers SDs as potential biomarker/precursor of future PD-neurodegeneration; the second direction, from PD to SDs, considers SDs as concomitant symptoms in manifest PD, mainly related to primary PD-neuropathology and/or parkinsonian drugs. Furthermore, for each direction, we questioned SDs-PD relationship in terms of risk factors, neuronal circuits/mechanisms, and impact on the clinical phenotype and disease progression. Future research is needed to investigate whether targeting sleep may be the winning strategy to treat PD, in the context of a personalized precision medicine.

Subjective sleep parameters: A marker to PTSD symptoms evolution? A 4-year longitudinal study.

Disturbed sleep is a common feature after exposure to a traumatic event, especially when PTSD develops. However, although there is evidence suggesting a potential role of sleep disturbance in the progression of PTSD symptoms, the interrelationship between sleep and PTSD symptoms has yet to be determined. In order to address this knowledge gap, we have investigated the influence of initial sleep characteristics on the evolution of post-traumatic stress disorder (PTSD) symptoms over 4 years of follow-up among individuals exposed to the Brazilian Kiss nightclub fire. Participants were individuals exposed to the 2013 Kiss nightclub fire in Brazil. Sleep characteristics and PTSD symptoms were measured within the 4 years following the fire by self-report questionnaires, such as The Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist - Civilian version (PCL-C). Generalized estimating equations (GEE) models were used to examine the longitudinal associations (by estimating the relative effects of initial sleep problems on PTSD symptoms after adjusting for covariates). Comprehensive information concerning socio-demographic factors, health status, and sleep complaints were obtained. A total of 232 individuals were included. In GEE models, no significant interactions were observed between sociodemographic variables and PTSD symptoms in the follow-up period, however, associations were found between PTSD at baseline and the following factors: the female gender, the victim individuals and the existence of prior psychiatric disease. Initial subjective sleep parameters were strongly associated with PTSD symptoms over 4 years, mainly the presence of disturbed dreams (p = 0.012), increased sleep latency (p = 0.029), and reduced sleep duration (p = 0.012). Sleep complaints and PTSD symptoms were common among individuals after the disaster. The current study has found that the presence of sleep complaints, especially increased sleep latency, presence of disturbed dreams and short sleep duration, in the initial presentation after the fire was consistently associated with the perpetration of PTSD symptoms in the next 4 years of follow-up. These findings suggest that interventions addressing these sleep complaints have the potential to reduce the persistence and/or severity of PTSD symptoms.

Alzheimer's disease and sleep disorders: A bidirectional relationship.

Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-ß (Aß) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) and nonrapid eye movement sleep (NREM), plays a key role in consolidating social and spatial memory. Emerging evidence has revealed that sleep disorders such as circadian disturbances and disruption of neuronal rhythm activity are considered as both candidate risks and consequence of AD, suggesting a bidirectional relationship between sleep and AD. This review will firstly grasp basic knowledge of AD pathogenesis, then highlight macrostructural and microstructural alteration of sleep along with AD progression, explain the interaction between accumulation of Aß and hyperphosphorylated tau, which are two critical neuropathological processes of AD, as well as neuroinflammation and sleep, and finally introduce several methods of sleep enhancement as strategies to reduce AD-associated neuropathology. Although theories about the bidirectional relationship and relevant therapeutic methods in mice have been well developed in recent years, the knowledge in human is still limited. More studies on how to effectively ameliorate AD pathology in patients by sleep enhancement and what specific roles of sleep play in AD are needed.

Efficient Sleep Stage Identification Using Piecewise Linear EEG Signal Reduction: A Novel Algorithm for Sleep Disorder Diagnosis.

Sleep is a vital physiological process for human health, and accurately detecting various sleep states is crucial for diagnosing sleep disorders. This study presents a novel algorithm for identifying sleep stages using EEG signals, which is more efficient and accurate than the state-of-the-art methods. The key innovation lies in employing a piecewise linear data reduction technique called the Halfwave method in the time domain. This method simplifies EEG signals into a piecewise linear form with reduced complexity while preserving sleep stage characteristics. Then, a features vector with six statistical features is built using parameters obtained from the reduced piecewise linear function. We used the MIT-BIH Polysomnographic Database to test our proposed method, which includes more than 80 h of long data from different biomedical signals with six main sleep classes. We used different classifiers and found that the K-Nearest Neighbor classifier performs better in our proposed method. According to experimental findings, the average sensitivity, specificity, and accuracy of the proposed algorithm on the Polysomnographic Database considering eight records is estimated as 94.82%, 96.65%, and 95.73%, respectively. Furthermore, the algorithm shows promise in its computational efficiency, making it suitable for real-time applications such as sleep monitoring devices. Its robust performance across various sleep classes suggests its potential for widespread clinical adoption, making significant advances in the knowledge, detection, and management of sleep problems.

Recent Insights into Hippocampal Dysfunction and Neuroplasticity in Sleep Disorders: An Update from Preclinical Studies.

Sleep disorders are prevalent neurological conditions linked to neurocognitive impairments. Understanding the neuroplasticity changes in the hippocampus, which plays a central role in regulating neurocognitive function, is crucial in the context of sleep disorders. However, research on neurodegenerative disorders and the influence of sleep disorders on hippocampal neuroplasticity remains largely unclear. Therefore, this review aims to highlight the latest advancements regarding hippocampal neuroplasticity and functional changes during sleep disorders, drawing insights from clinical and preclinical research involving sleep-deprived animal models. These articles were gathered through comprehensive literature searches across databases, including Google Scholar, PubMed, Web of Science, and Scopus. Maternal sleep deprivation has been observed to cause neurocognitive impairment in offspring, along with changes in protein expression levels associated with neuroplasticity. Similarly, sleep deprivation in adult mice has been shown to affect several cognitive functions and fear extinction without influencing the acquisition of fear conditioning. While mechanistic research on neurocognitive dysfunction induced by maternal and adult sleep deprivation is limited, it suggests the involvement of several signaling pathways, including neurotrophic factors, synaptic proteins, and inflammatory molecules, which are triggered by sleep deprivation. Further studies are needed to clarify the mechanistic pathways underlying hippocampal dysfunction and synaptic alterations associated with sleep disturbances.

Microglia and Sleep Disorders.

Sleep is a physiological state that is essential for maintaining physical and mental health. Sleep disorders and sleep deprivation therefore have many adverse effects, including an increased risk of metabolic diseases and a decline in cognitive function that may be implicated in the long-term development of neurodegenerative diseases. There is increasing evidence that microglia, the resident immune cells of the central nervous system (CNS), are involved in regulating the sleep-wake cycle and the CNS response to sleep alteration and deprivation. In this chapter, we will discuss the involvement of microglia in various sleep disorders, including sleep-disordered breathing, insomnia, narcolepsy, myalgic encephalomyelitis/chronic fatigue syndrome, and idiopathic rapid-eye-movement sleep behavior disorder. We will also explore the impact of acute and chronic sleep deprivation on microglial functions. Moreover, we will look into the potential involvement of microglia in sleep disorders as a comorbidity to Alzheimer's disease and Parkinson's disease.

Restless Legs Syndrome Affects Sleep in de novo Parkinson's Disease Patients.

BACKGROUND: Restless legs syndrome (RLS) is common in Parkinson's disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. OBJECTIVE: This study aimed to identify the clinical factors affected by RLS in patients with PD. METHODS: We included 369 de novo PD patients. RLS was assessed by face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RESULTS: RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the sleep/fatigue domain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. CONCLUSIONS: RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.

Joint effects of sleep disturbance and renal function impairment on incident new-onset severe metabolic dysfunction-associated steatotic liver disease.

AIM: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD. RESULTS: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk. CONCLUSIONS: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.