Boosting obstructive sleep apnea therapy by non-pharmacological approaches: A network meta-analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common breathing-related sleep disorder with a considerable economic burden, low diagnosis and treatment rates. Continuous positive airway pressure (CPAP/PAP) is the principal therapy for OSA treatment; nevertheless, effectiveness is often limited by suboptimal adherence. The present network meta-analysis aims to systematically summarize and quantify different interventions' effects on CPAP/PAP adherence (such as mean usage CPAP or PAP in hours per night) in OSA patients, comparing Behavioral, Educational, Supportive and Mixed interventions in Randomized Control Trials (RCT). METHODS: We conducted a computer-based search using the electronic databases of Pubmed, Psycinfo, Scopus, Embase, Chinal and Medline until August 2022, selecting 50 RCT. RESULTS: By means of a random effect model network meta-analysis, results suggested that the most effective treatment in improving CPAP/PAP adherence was the Supportive approach followed by Behavioral Therapy focused on OSA treatment adherence. CONCLUSION: This network meta-analysis might encourage the most experienced clinicians and researchers in the field to collaborate and implement treatments for improving CPAP/PAP treatment adherence. Moreover, these results support the importance of multidisciplinary approaches for OSA treatment, which should be framed within a biopsychological model.

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

Challenging subjective excessive daytime sleepiness as an insomnia symptom: a retrospective study.

Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT-I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre-post evaluation of the ESS in a sub-sample of patients with ID who underwent CBT-I. Component 2 of the Insomnia Severity Index and Profile of Mood States-Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT-I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.

Non-pharmacological and melatonin interventions for pediatric sleep initiation and maintenance problems: A systematic review and network meta-analysis.

Sleep initiation and maintenance problems are common in the pediatric population and while behavioral interventions are recommended, their efficacy remains to be evaluated in clinical trials. We conducted a systematic review and network meta-analysis to assess the efficacy of non-pharmacological treatments and melatonin for sleep initiation and maintenance problems in healthy pediatric populations. We included 30 studies in the systematic review and 15 in the meta-analysis. Three network meta-analyses were conducted for sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time (TST). For SOL variable, the results support greater effectiveness of light therapy and melatonin than evidence-based psychological interventions, whether implemented in combination with light therapy or not. Regarding WASO variable, evidence-based psychological interventions and a combination of those techniques plus light treatment were the most efficacious. Finally, for TST variable, a larger effect was shown for the combined treatment of evidence-based psychological intervention with light therapy in comparison to other interventions. In conclusion, we found a high variability between study protocols likely impacting the results of the meta-analysis. Future randomized control trials studies, stratified by pediatric age classes, are needed in order to provide clear suggestions in clinical settings.

A data-driven approach to neuropsychological features in isolated REM behaviour disorder: A latent class analysis.

Recent evidence demonstrated that neuropsychological assessment may be considered a valid marker of neurodegeneration in idiopathic REM sleep behaviour disorder (iRBD). However, little is known about the possible neuropsychological heterogeneity within the iRBD population. This retrospective study aimed to identify and describe different neuropsychological phenotypes in iRBD patients by means of a data-driven approach using latent class analysis. A total of 289 iRBD patients underwent a neuropsychological assessment evaluating cognitive domains: global cognition, language, short- and long-term memory, executive functions and visuospatial abilities. The presence of mild cognitive impairment (MCI) was also assessed. Latent class analysis was carried out to identify iRBD subtypes according to neuropsychological scores. The most parsimonious model identified three latent classes. Groups were labelled as follows: Class 2 "severely impaired" (n = 83/289): mean pathological scores in different tests, a high percentage of MCI multiple-domain and impairment in all neuropsychological domains. Class 1 "moderately impaired" (n = 44/289): mean neuropsychological score within the normal value, a high percentage of MCI (high risk to phenoconversion) and great impairment in the visuospatial domain. Class 3 "slightly impaired" (n = 162/289): no deficit worthy of attention except for short- and long-term memory. Our results suggest three different clinical phenotypes within the iRBD population. These findings may be relevant in the future for predicting the clinical trajectories of phenoconversion in iRBD.

"Thinking About Thinking" in Insomnia Disorder: The Effect of Cognitive-Behavioral Therapy for Insomnia on Sleep-Related Metacognition.

Metacognition is defined as the ability to reflect on one's mental state and to govern thoughts and beliefs. Metacognitive dysfunctions are typical of several psychopathologic conditions, and also a feature of insomnia disorder, possibly playing a crucial role in its genesis and maintenance. In the context of insomnia, metacognition describes how individuals react to their own sleep-related thoughts and beliefs, boosting the hyperarousal state experienced by these patients. Up to now, no studies evaluated the effect of cognitive behavioral therapy for insomnia (CBT-I) on metacognitive functioning. Therefore, the aim of our study was to evaluate the effect of CBT-I administered in group format in patients with insomnia disorder. As expected, all patients showed significant improvements in both insomnia and sleep diary parameters after treatment. Furthermore, an improvement was observed also in dysfunctional metacognitive levels, assessed by means of the Metacognitions Questionnaire-Insomnia (MCQ-I). However, 63% of patients still showed a MCQ-I score above the clinical cutoff after treatment. Dividing the sample on the basis of MCQ-I questionnaire scores after CBT-I, we found that patients, who still presented metacognitive impairment, received significant beneficial effects from CBT-I both on insomnia symptoms and on dysfunctional beliefs, but not on dysfunctional metacognitive functioning. These findings suggest that metacognition should be carefully evaluated in insomnia patients and further studies are needed to evaluate long-term implications of this remaining dysfunction.

Depressive and stress symptoms in insomnia patients predict group cognitive-behavioral therapy for insomnia long-term effectiveness: A data-driven analysis.

BACKGROUND: Insomnia Disorder is characterized by high degree of phenotypic heterogeneity, that might influence treatment response. METHODS: 123 of 294 insomnia patients initially recruited (66.7% females, age=40.59±11.89) were assessed before and after group Cognitive-Behavioral Therapy for Insomnia (CBT-I), as well as at follow-up (7.8±1.6 years after the end-of-treatment). By use of latent class analysis (LCA) we identified insomnia subtypes according with baseline scores of insomnia severity and features, anxiety, depression, stress and sleepiness symptoms, circadian rhythm, and treatment effectiveness (Delta score of Insomnia Severity Index-ISI between baseline and end-of-treatment). RESULTS: By LCA we revealed three classes: "PURE INSOMNIA", "INSOMNIA+ANXIETY+DEPRESSION+STRESS", and "INSOMNIA+ANXIETY". The improvements in insomnia severity was maintained up to 10 years after the end-of-treatment, but with differences between classes (p<0.05). Class "INSOMNIA+ANXIETY+DEPRESSION+STRESS" showed at the end-of-treatment the largest percentage of responders (63.5% = Insomnia Severity Index decrease ≥8). However, at follow up the effect was less and 48.1% had a moderate or severe insomnia (Insomnia Severity Index >14). LIMITATIONS: The lack of a control group and the absence of a complete clinical assessment at the follow-up limit the interpretability of our results. CONCLUSIONS: Our data driven analysis suggest insomnia heterogeneity can be categorized into sub-classes by depression, anxiety, and stress symptoms. In addition, insomnia patients with stress and depression symptoms maintained highest percentage of clinical depression at the end-of-treatment and insomnia at follow-up, in comparison with others classes. Stress and depression symptoms should be considered risk factors that play an important role in the long-term outcome of CBT-I.

The reliability of objective total sleep time in predicting the effectiveness of cognitive-behavioral therapy for insomnia.

BACKGROUND: Despite insomnia diagnosis is based only on subjective sleep assessment, recent literature suggested the usefulness of objective sleep duration for the identification of two insomnia phenotypes based on objective total sleep time (oTST). In particular, insomnia with short sleep duration (SS) (oTST<6 h) seems to receive less benefit from Cognitive-Behavioral Therapy for Insomnia (CBT-I) compared to patients with normal sleep duration (NS) (oTST≥6 h). The aim of this study is to evaluate CBT-I response of patients previously divided into SS and NS and to assess the agreement between oTST measured by polysomnography (PSG) and by actigraphy in identifying the two subgroups. METHODS: Fifty-three insomnia patients (50.9% females; mean age 56.53 ± 11.43) underwent a baseline PSG and an actigraphic evaluation to identify SS and NS subjects. Insomnia Severity Index (ISI) and sleep diaries data (wakefulness after sleep onset) were considered primary outcomes. All the other sleep diaries variables were used as secondary outcomes. RESULTS: Throughout PSG we identified 22 NS (41.5%) and 31 SS (58.5%) patients, whereas actigraphic evaluation identified 38 NS (71.7%) and 15 SS (28.3%) patients. All subjects showed significant improvement after treatment, however, no effect of group membership was found to influence CBT-I response. Strikingly, actigraphy and PSG differed in identifying the two subgroups. Specifically, only 27 out 53 (51%) were consistently classified as SS [K = 0.086, 95% confidence interval: -0.132 to 0.305, p = 0.448]. CONCLUSIONS: Our results challenge the reliability and usefulness of oTST in predicting CBT-I effectiveness. Future studies might focus on night-to-night variability experienced by insomnia patients for the prediction of CBT-I outcomes.

Impact of pre-sleep habits on adolescent sleep: an Italian population-based study.

OBJECTIVE: Several evidences demonstrate that pre-sleep habits may negatively impact adolescent sleep, yet few data exist on Italian population. This study aimed to investigate the relationship between pre-sleep habits, use of technology/activity and sleep in Italian adolescents. METHODS: Self-report questionnaires including Italian version of School Sleep Habits Survey and use of technology/activity (eg smartphone, PC) at bedtime were administered to 972 adolescents (13-19 years) from Lombardia. We stratified the sample in five groups according to the age: Group I (13-14 years), Group II (15 years), Group III (16 years), Group IV (17 years), Group V (18-19 years). RESULTS: Our descriptive analysis reveals a different sleep profile across age-groups: Group III showed highest percentage of bad sleep (26.7%) and frequent nocturnal awakenings (24.1%), Group V had the highest percentage of insufficient sleep (40,4%) and difficulty falling asleep (42.7%) and Group IV presented an elevated difficulty in waking up in the morning (70.1%). A significant negative correlation was found in total group between use of smartphone, internet and studying/doing homework and total sleep time. The use of smartphone, internet videogames, listening to music and studying/doing homework was positively associated with delayed bedtime. CONCLUSIONS: This study confirms the great impact of pre-sleep habits, and in particular the use of technology on adolescent sleep. Our results demonstrate that sleep is strongly altered among Italian adolescents using electronic devices in evening. The type of technology may be related to specific sleep profile, emphasizing the importance of stratification analyses to identify associated factors to sleep problems.

The association between emotional dysregulation and REM sleep features in insomnia disorder.

Rapid Eye Movement (REM) sleep is involved in nightly emotional processing; therefore, its disruption might be associated with an impaired ability of emotional regulation during daytime. Accordingly, the aim of the present study was to evaluate the presence of emotional dysregulation in insomnia patients and to test its correlation with REM sleep features. Forty-six subjects (23 insomnia patients and 23 healthy controls) were enrolled. All subjects underwent an assessment for the evaluation of emotion dysregulation (Difficulties in Emotion Regulation Scale, DERS), sleep quality, insomnia severity, excessive daytime sleepiness, worry, rumination, depressive and anxious symptomatology. Insomnia patients underwent a nocturnal polysomnographic recording to characterize sleep macrostructure and REM sleep microstructure variables. Insomnia patients reported increased values of emotional dysregulation. REM sleep percentage and REM sleep latency significantly correlated with DERS total score, and with the subscales "Lack of Confidence in Emotional Regulation Skills", "Difficulties in Behavioral Control" and "Difficulty in recognizing emotions". Furthermore, positive correlations between REM arousal index and emotion dysregulation were found, whereas REM density negatively correlated with DERS. Our results suggest the presence of a relationship between REM sleep and emotional regulation in insomnia patients.

Insomnia Patients With Subjective Short Total Sleep Time Have a Boosted Response to Cognitive Behavioral Therapy for Insomnia Despite Residual Symptoms.

Background: Two distinct insomnia disorder (ID) phenotypes have been proposed, distinguished on the basis of an objective total sleep time less or more than 6 hr. In particular, it has been recently reported that patients with objective short sleep duration have a blunted response to cognitive behavioral therapy for insomnia (CBT-I). The aim of this study was to investigate the differences of CBT-I response in two groups of ID patients subdivided according to total sleep time. Methods: Two hundred forty-six ID patients were subdivided into two groups, depending on their reported total sleep time (TST) assessed by sleep diaries. Patients with a TST greater than 6 hr were classified as "normal sleepers" (NS), while those with a total sleep time less than 6 hr were classified as "short sleepers" (SS). Results: The delta between Insomnia Severity Index scores and sleep efficiency at the beginning as compared to the end of the treatment was significantly higher for SS in comparison to NS, even if they still exhibit more insomnia symptoms. No difference was found between groups in terms of remitters; however, more responders were observed in the SS group in comparison to the NS group. Conclusions: Our results demonstrate that ID patients with reported short total sleep time had a beneficial response to CBT-I of greater magnitude in comparison to NS. However, these patients may still experience the presence of residual insomnia symptoms after treatment.

Impact Of Phenotypic Heterogeneity Of Insomnia On The Patients' Response To Cognitive-Behavioral Therapy For Insomnia: Current Perspectives.

Insomnia is one of the most common mental disorders and the most frequent sleep disorder encountered in clinical practice, with a prevalence of about 7% in the European population. Insomnia Disorder (ID) is defined as a disturbance of sleep initiation or maintenance, followed by a feeling of non-restorative sleep and several diurnal consequences ranging from occupational and social difficulties to cognitive impairment. Cognitive-Behavioral Therapy for Insomnia (CBT-I) is considered the first-choice therapy for this disorder because its effectiveness has been proven to be greater in the long term with fewer side effects in comparison to pharmacotherapy. Although its effectiveness has been well established, it has been reported that nearly 40% of patients do not achieve remission after treatment. This finding could be the consequence of heterogeneity of ID between patients. It has been proposed that this heterogeneity might be ascribable to indices that are not related to sleep quality and quantity, such as comorbidities, life events, and personality traits. However, several works focused on the role of sleep markers, in particular objective total sleep time, for the phenotypization of ID and treatment response. The aim of this work is to summarize the available scientific literature regarding the impact of ID subtype on CBT-I response.

Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder.

Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). Therefore, a timely identification of biomarkers able to predict an early conversion into neurodegeneration is of utmost importance. Areas covered: In this review, the authors provide updated evidence regarding the presence of neuropsychological, electrophysiological and neuroimaging markers in isolated RBD (iRBD) patients when the neurodegeneration is yet to come. Expert opinion: Cognitive profile of iRBD patients is characterized by the presence of impairment in visuospatial abilities and executive function that is observed in α-synucleinopathies. However, longitudinal studies showed that impaired executive functions, rather than visuospatial abilities, augmented conversion risk. Cortical slowdown during wake and REM sleep suggest the presence of an ongoing neurodegenerative process paralleled by cognitive decline. Neuroimaging findings showed that impairment nigrostriatal dopaminergic system might be a good marker to identify those patients at higher risk of short-term conversion. Although a growing body of evidence the identification of biomarkers still represents a critical issue in iRBD.

Long-term clinical effect of group cognitive behavioral therapy for insomnia: a case series study.

OBJECTIVE: Cognitive-behavioral therapy for insomnia (CBT-I) is recognized as the first-choice intervention for insomnia. One of the best-known advantages of CBT-I in comparison with pharmacotherapy is its long-term effect. However, only few studies have assessed its benefits with follow-up periods of longer than three years. In this clinical case series study we aimed to describe the long-term effects of group CBT-I after a mean 7.8 ± 1.6 years of follow-up (range 4-10 years). METHODS: A total of 292 insomnia disorder (ID) patients were consecutively enrolled at the Sleep Disorders Center of San Raffaele Hospital, Milan; 123 patients (82 (66.7%) females and 41 (33.3%) males, mean age 40.59 ± 11.89 years) completed the follow-up evaluation within a range of 4-10 years. RESULTS: In the 258 patients who completed the treatment, insomnia severity index (ISI) total score improved significantly as well as all variables of the sleep diaries. Using ISI as the primary outcome, we demonstrated that the effect of CBT-I is maintained up to 10 years after the end of treatment. Furthermore, we found that patients that used only CBT-I techniques to deal with relapses were the ones with better outcomes, in particular compared to the patients that re-used medications. CONCLUSION: To the best of our knowledge this is the longest follow-up evaluation in the literature, both for group and individual CBT-I. These findings have an important clinical implication both suggesting and confirming that CBT-I can be considered the treatment of choice for insomnia.

Daytime sleepiness: more than just Obstructive Sleep Apnea (OSA).

Excessive Daytime Sleepiness (EDS) is a common condition with a significant impact on quality of life and general health. A mild form of sleepiness can be associated with reduced reactivity and modest distractibility symptoms, but more severe symptomatic forms are characterized by an overwhelming and uncontrollable need to sleep, causing sudden sleep attacks, amnesia and automatic behaviors. The prevalence in the general population is between 10 and 25%. Furthermore, EDS has been considered a core symptom of obstructive sleep apnea (OSA), as well as being the main symptom of primary hypersomnias such as narcolepsy types 1 and 2, and idiopathic hypersomnia. Moreover, it can be considered secondary to other sleep disorders (Restless Legs Syndrome, Chronic insomnia, Periodic Limb Movements), psychiatric conditions (Depression, Bipolar Disorder) or a consequence of the intake/abuse of drugs and/or substances. An accurate medical history cannot be sufficient for the differential diagnosis, therefore instrumental recordings by means of polysomnography and the Multiple Sleep Latency Test (MSLT) are mandatory for a correct diagnosis and treatment of the underlying cause of EDS.