Sleep medicine最新文献

Objectives

Pre-sleep stress or hyperarousal is a known key etiological component in insomnia disorder. Despite this, physiological alterations during the sleep onset are not well-understood. In particular, insomnia and obstructive sleep apnea (OSA) are highly prevalent co-morbid conditions, where autonomic regulation may be altered. We aimed to characterize heart rate variability (HRV) during sleep onset as a potential measure of pre-sleep hyperarousal.

Methods

We described the profile of pre-sleep HRV measures and explore autonomic differences in participants with self-reported insomnia disorder (with no OSA, n = 69; with mild OSA, n = 70; with moderate or severe OSA, n = 66), compared to normal sleep controls (n = 123). Heart rate data during the sleep onset process were extracted for HRV analyses.

Results

During the sleep onset process, compared to normal sleep controls, participants with insomnia had altered HRV, indicated by higher heart rate (p = 0.004), lower SDNN (p = 0.003), reduced pNN20 (p < 0.001) and pNN50 (p = 0.010) and lower powers (p < 0.001). Participants with insomnia and moderate/severe OSA may have further deteriorated HRV outcomes compared to no/mild OSA patients with insomnia but differences were not significant. Insomnia itself was associated with significantly higher heart rate, lower pNN20, and lower high frequency power even after adjustment for age, gender, BMI and OSA severity.

Conclusions

Participants with insomnia had lower vagal activity during the sleep onset period, which may be compounded by OSA, reflected in higher heart rates and lower HRV. These altered heart rate dynamics may serve as a physiological biomarker for insomnia during bedtime wakefulness, or as a potential tool to evaluate the efficacy of behavioral interventions which target bedtime stress.

Objectives

This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD).

Methods

Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I).

Results

In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes.

Conclusion

The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.

Objective

Previous studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship.

Methods

Firstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.

Results

The results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates.

Conclusions

This study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

Objectives

The current literature lacks a clear evaluation of the effectiveness of Cognitive Behavioral Therapy for Insomnia (CBT-I) on acute insomnia. Our study aims to address this issue through a systematic review and meta-analysis of Randomized Controlled Trials (RCTs).

Method

We systematically searched PubMed, Embase, and Cochrane Library in April 2024 for RCTs comparing patients with clinically significant insomnia symptoms for less than 6 months (ie, acute insomnia) assigned to 1–6 weeks of CBT-I versus no CBT-I.

Results

We included four RCTs comprising 327 patients with acute insomnia, of whom 162 (49.5 %) were randomized to CBT-I. CBT-I significantly reduced the Insomnia Severity Index score (MD –5.28; 95 % CI −6.01, −4.56; p < 0.00001; I² = 18 %), the incidence of chronic insomnia (MD 0.50; 95 % CI 0.35, 0.70; p < 0.0001; I² = 0 %), and the sleep latency (MD -11.04; 95 % CI –18.46, −3.61; p = 0.004; I² = 0 %).

Conclusion

These findings provide preliminary evidence that minimal CBT-I may be a feasible and effective preventive measure against chronic insomnia. However, future RCTs and effectiveness trials are necessary to validate, with greater statistical power, the hypothesis that CBT-I can prevent transition from acute to chronic insomnia, given the limited number of studies in our meta-analysis.

Objective

This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.

Patients/methods

490 patients with insomnia disorder from 95 sites in Japan were randomized to daridorexant 50 mg (n = 163), 25 mg (n = 163) or placebo (n = 164) for 4 weeks, followed by a 7-day placebo run-out and a 30-day safety follow-up. The primary efficacy endpoints, in hierarchical order, were change from baseline at Week 4 in subjective total sleep time (sTST) and subjective latency to sleep onset (sLSO), for daridorexant 50 mg vs placebo. sTST and sLSO were also evaluated (secondary endpoints) for daridorexant 25 mg vs placebo. Safety endpoints included adverse events and next-morning sleepiness (Visual Analog Scale, VAS).

Results

Daridorexant 50 mg significantly increased sTST and decreased sLSO versus placebo at Week 4 (least-squares mean difference [LSMD]: sTST 20.3 min [95 % CI 11.4, 29.2] p < 0.001; sLSO −10.7 min [−15.8, −5.5] p < 0.001). Daridorexant 25 mg also significantly improved both endpoints versus placebo (LSMD: sTST 9.2 min [0.3, 18.1] p = 0.042; sLSO −7.2 min [-12.3, −2.0] p = 0.006). Overall incidence of adverse events was similar across groups (50 mg: 22 %; 25 mg: 18 %; placebo 23 %); somnolence, the most common event, increased with increasing dose (50 mg: 6.8 %; 25 mg: 3.7 %; placebo 1.8 %). However, daridorexant did not increase VAS next-morning sleepiness. No rebound or withdrawal-related symptoms were observed after treatment discontinuation.

Conclusions

In Japanese patients with insomnia disorder, daridorexant (25 and 50 mg) was well tolerated and significantly improved subjective sleep outcomes, with no evidence of residual effects.

Background

The arousal state has been demonstrated to be involved in the fundamental pathophysiological mechanism of sleep disturbances. Tai chi (TC) and repetitive transcranial magnetic stimulation (rTMS) have been documented to alleviate sleep disturbances by interfering with different arousal components. It is reasonable to assume that combining TC and rTMS could induce synergistic and longer-lasting benefits for sleep disturbances.

Methods

Thirty-eight older community-dwelling people were randomly assigned to one of three groups: TC plus rTMS (n = 12), TC alone (n = 13), and treat-as-usual (TAU) (n = 13). The interventions were conducted three times per week for 4 weeks for the two intervention groups. The primary outcome was the insomnia severity, while the secondary outcomes were the actigraphy-assessed sleep patterns, use of hypnotic medications, mood states, and quality of life. The mediator outcomes included self-reported somatic arousal and cognitive arousal as well as electroencephalogram (EEG)-assessed cortical arousal. The assessments were conducted at baseline (T0), post-intervention (T1), and 3-month follow-up (T2).

Results

Significant improvements in the insomnia severity were observed in the TC plus rTMS group compared with the TAU group at T1 (Cohen's d = 1.62, p = 0.003) and T2 (Cohen's d = 1.97, p < 0.001). In contrast, significant improvements in the TC alone group were found only at T2 (Cohen's d = 1.03, p = 0.010) when compared with the TAU group. Significant interaction effects were noted on the actigraphy-assessed sleep efficiency (p = 0.015) and total sleep time (p = 0.004), depression (p = 0.003) and stress scores (p = 0.002), and mental function in relation to quality of life (p = 0.042). However, none of the mediators elucidated how combining TC and rTMS could improve the insomnia severity.

Conclusion

The research findings are expected to guide further clinical practice in the management of sleep disturbances among older adults using various interventions. Future studies are needed to unravel the underlying mechanism and optimize the protocol to maximize the therapeutic benefits.

The aims were (i) to determine the effects of Cognitive behavioral therapy for insomnia (CBT-I) on sleep disturbances, pain intensity and disability in patients with chronic musculoskeletal pain (CMP), and (ii) to determine the dose-response association between CBT-I dose (total minutes) and improvements in sleep disorders, pain intensity and disability in patients with CMP. A comprehensive search was conducted in PubMed/MEDLINE, Web of Science, CINAHL, and SCOPUS until December 17, 2023. Randomized clinical trials (RCTs) using CBT-I without co-interventions in people with CMP and sleep disorders were eligible. Two reviewers independently extracted data and assessed risk of bias and certainty of the evidence. A random effects meta-analysis was applied to determine the effects on the variables of interest. The dose-response association was assessed using a restricted cubic spline model. Eleven RCTs (n = 1801 participants) were included. We found a significant effect in favor of CBT-I for insomnia (SMD: −1.34; 95%CI: −2.12 to −0.56), with a peak effect size at 450 min of CBT-I (−1.65, 95%CI: −1.89 to −1.40). A non-significant effect was found for pain intensity. A meta-analysis of disability was not possible due to the lack of data. This review found benefits of CBT-I for insomnia compared to control interventions, with a large effect size. In addition, it was estimated that a 250-min dose of CBT-I had a large effect on reducing insomnia and that the peak effect was reached at 450 min. These novel findings may guide clinicians in optimizing the use of CBT-I in people with CMP and insomnia.

Background

The medullary nucleus of solitary tract (NTS) and its afferents of vagus nerve have long been investigated in regulation of cortical activity and sleep promotion. However, the underlying neural circuit by which the NTS regulates electroencephalogram (EEG) and sleep remain unclear. As the NTS has a strong projection to the pontine arousal site, the parabrachial nucleus (PB), we proposed the NTS via the pontine parabrachial nucleus (PB) regulates cortical activity and sleep.

Methods

We bilaterally and directly stimulated the NTS neurons by chemogenetic approach and NTS terminals in the PB by optogenetic approach and examined changes in EEG and sleep in rats.

Results

Opto- and chemo-stimulation of the NTS and NTS-PB pathway altered neither sleep amounts nor patterns; however, both stimulations consistently increased EEG delta (0.5–4.0 Hz) EEG power during non-rapid-eye-movement (NREM) sleep and alpha-beta (10–30 Hz) EEG power during wake and REM sleep.

Conclusion

Our results indicate that the NTS via its projections to the PB synchronizes low frequency EEG during NREM sleep and high frequency EEG during wake and REM sleep. This pathway may serve the neural foundation for the vagus nerve stimulation (VNS) treating cortical disorders.

Introduction

Recent studies suggest the existence of a physiologic basis for bone rarefaction and increased risk for fractures. This study aimed to address anthropometric differences between patients with narcolepsy type 1 (NT1) and type 2 (NT2) and discrepancies in bone mineral content (BMC) as a function of hypocretin-1 (Hcrt-1) measured in cerebrospinal fluid (CSF).

Methods

We have evaluated 31 adult patients (aged 18–65 years) with NT1 and 18 patients with NT2, comparing the groups in terms of anthropometric variables – body mass index (BMI) and waist-to-hip ratio (WHR) – and percentage of bone mineral content (%BMC), measured by bioelectrical impedance analysis (BIA). Statistical analysis assessed the effects of Hcrt-1 levels on CSF, dietary intake, and medication use over these variables. Statistical significance was achieved with a confidence interval of 95 % and p < 0.05.

Results

Patients with NT1 presented with higher BMI (32.04 ± 6.95 vs. 25.38 ± 4.26 kg/m²; p < 0.01) and WHR (0.89 ± 0.09 vs. 0.83 ± 0.09; p = 0.02) compared to NT2, in detriment of %BMC, which was lower for NT1 (4.1 ± 1.02 vs. 4.89 ± 0.59; p < 0.01). Hcrt-1 in CSF showed a positive correlation with %BMC (r = +0.48, p < 0.01) and a negative correlation with anthropometric features (BMI: r = −0.54, p < 0.01; WHR: r = −0.37, p = 0.01). There was a correlation between WHR and diary caloric intake (r = +0.42, p < 0.01).

Conclusion

The evaluation of patients with narcolepsy presupposes a syndromic approach comprising symptoms that go far beyond excessive daytime sleepiness. The integrated follow-up, including nutritional profile and anthropometric features, should add value in reducing morbidity in this population.

Objectives

Optimal sleep is crucial for developing and maintaining gifted children's cognitive abilities. However, only a few studies have explored the sleep profiles of gifted children and overlooked their internal variations. This study aimed to investigate subjective and object sleep profiles in school-aged gifted children with different levels of giftedness.

Methods

This study included 80 school-aged children (50 % male) aged 6–11 years. Giftedness was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). Subjective and objective sleep were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and Actiwatch 2.

Results

The sample was divided into three groups based on their full scale intelligence quotient (IQ): 16 typically developing children (IQ < 130), 38 moderately gifted children (IQ: 130–145), and 26 highly gifted children (IQ > 145). The highly gifted children had the mildest sleep problems, particularly in sleep duration and daytime sleepiness. Moderately gifted children had the shortest subjective average sleep duration, while the three groups had no significant differences in Actiwatch-measured sleep variables. Furthermore, CSHQ total and daytime sleepiness subscale scores were negatively associated with the full scale IQ in gifted children after controlling for confounders including emotional and behavioral problems.

Conclusions

Children with higher levels of giftedness experience fewer subjective sleep problems but have similar objective sleep parameters. It is imperative to implement tailored sleep strategies for fostering intellectual development and nurturing young talents.