Genetics and epigenetics of rare hypersomnia.

Herein we focus on connections between genetics and some central disorders of hypersomnolence - narcolepsy types 1 and 2 (NT1, NT2), idiopathic hypersomnia (IH), and Kleine-Levin syndrome (KLS) - for a better understanding of their etiopathogenetic mechanisms and a better diagnostic and therapeutic definition. Gene pleiotropism influences neurological and sleep disorders such as hypersomnia; therefore, genetics allows us to uncover common pathways to different pathologies, with potential new therapeutic perspectives. An important body of evidence has accumulated on NT1 and IH, allowing a better understanding of etiopathogenesis, disease biomarkers, and possible new therapeutic approaches. Further studies are needed in the field of epigenetics, which has a potential role in the modulation of biological specific hypersomnia pathways.

The Epworth sleepiness scale may have more advantages than the multiple sleep latency test in assessing sleepiness in patients with obstructive sleep apnea.

This study aimed to analyze the brain function of severe obstructive sleep apnea patients with various sleepiness assessment methods and explore the brain imaging basis for the differences between these methods. This study included 30 severe obstructive sleep apnea patients and 19 healthy controls. Obstructive sleep apnea patients were divided into a subjective excessive daytime sleepiness group and a subjective non-excessive daytime sleepiness group according to the Epworth sleepiness scale. Moreover, they were divided into an objective excessive daytime sleepiness group and an objective non-excessive daytime sleepiness group according to the multiple sleep latency test. The fractional amplitude of low-frequency fluctuation was used to assess the features of brain function. Compared with healthy controls, participants in the subjective excessive daytime sleepiness group exhibited higher fractional amplitude of low-frequency fluctuation signals in the right thalamus, left cerebellar lobe 6, left putamen, and pallidum. Participants in the objective excessive daytime sleepiness group showed higher fractional amplitude of low-frequency fluctuation signals in the right thalamus and lower fractional amplitude of low-frequency fluctuation signals in the right superior frontal gyrus, the dorsolateral and superior frontal gyrus, and the medial orbital. We concluded that the thalamus may be involved in subjective and objective sleepiness regulation. Functional abnormalities in the putamen and pallidum may be involved in subjective sleepiness, whereas the frontal lobe may be involved in objective sleepiness.

Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. METHODS: This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. RESULTS: Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). INTERPRETATION: Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. FUNDING: Progressive Ladies Welfare Association.

Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers.

Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20-89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7-8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings.SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.

Idiopathic hypersomnia years after the diagnosis.

Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

Pre-pandemic circadian phase predicts pandemic alcohol use among adolescents.

Later circadian timing during adolescence is linked to worse sleep, more severe depression and greater alcohol involvement, perhaps due to circadian misalignment imposed by early school schedules. School schedules shifted later during the COVID-19 pandemic, ostensibly reducing circadian misalignment and potentially mitigating problems with depression and alcohol. We used the pandemic as a natural experiment to test whether adolescent drinkers with later circadian timing showed improvements in sleep, depression and alcohol involvement. Participants were 42 adolescents reporting alcohol use. We assessed circadian phase via dim light melatonin onset prior to the pandemic, then conducted remote assessments of sleep, depressive symptoms and alcohol use during the pandemic. Mixed-effects models were used to test for pandemic effects, covarying for age, sex, time since baseline evaluation, and current school/work status. Adolescents with later circadian timing reported less sleep than other teens on school nights, both before and during the pandemic. Although school night sleep increased during the pandemic (F = 28.36, p < 0.001), those increases were not greater for individuals with later circadian timing. Individuals with later circadian timing reported larger increases in alcohol use than other teens during the pandemic (X2 = 36.03, p < 0.001). Depressive symptoms increased during the pandemic (X2 = 46.51, p < 0.001) but did not differ based on circadian timing. Consistent with prior reports, adolescents with later circadian timing obtained less sleep, and later school schedules facilitated increased sleep duration. Nonetheless, individuals with later circadian timing reported the sharpest increases in alcohol use, suggesting that circadian timing contributes to risk for alcohol use beyond the effects of insufficient sleep.

Preliminary evidence of psychological improvements and increased maternal-fetal attachment associated with a mindfulness sleep programme: secondary analysis of uncontrolled data in 11 pregnant women with insomnia disorder.

Treating insomnia during pregnancy improves sleep and depressed mood. However, given well-established links between poor sleep and a broad spectrum of adverse maternal outcomes, the benefits of insomnia care may reach beyond sleep and depression. The present study evaluated the preliminary efficacy of 'Perinatal Understanding of Mindful Awareness for Sleep' (PUMAS)-a mindfulness sleep programme tailored to pregnancy that combines behavioural sleep strategies and meditation-for enhancing everyday mindfulness and maternal-fetal attachment, as well as for alleviating anxiety, repetitive thinking, and sleep-related daytime impairment. We conducted a secondary analysis of a single-arm proof-of-concept trial of 11 pregnant women with fifth edition of the Diagnostic and Statistical Manual of Mental Disorders diagnosed insomnia disorder who completed PUMAS (six sessions), which was delivered in an individual format via telemedicine video. Pre- and post-treatment outcomes included the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), Maternal-Fetal Attachment Scale (MFAS), Generalised Anxiety Disorder seven-item survey (GAD-7), Perseverative Thinking Questionnaire (PTQ), Daytime Insomnia Symptoms Response Scale (DISRS), and the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Scale (PROMIS-SRI). Symptom changes were evaluated with paired-samples t tests. Results showed PUMAS patients reported large increases in CAMS-R (Cohen's dz = 1.81) and medium-large increases in MFAS scores (Cohen's dz = 0.73). Moreover, PUMAS patients reported large reductions in scores on the GAD-7 (Cohen's dz = 1.09), PTQ (Cohen's dz = 1.26), DISRS (Cohen's dz = 1.38), and PROMIS-SRI (Cohen's dz = 1.53). Preliminary evidence suggests that a mindfulness-based perinatal sleep programme may benefit several domains of maternal wellbeing beyond sleep and depression. PUMAS substantially enhanced patient ratings of everyday mindfulness and maternal-fetal attachment, while reporting alleviations in anxiety, perseverative thinking, insomnia-focused rumination, and sleep-related daytime impairment.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

Hypersomnia in anti-glutamic acid decarboxylase 65 (GAD65) associated neurological syndromes: A pilot study.

BACKGROUND AND PURPOSE: Despite their detrimental impact on the quality of life in autoimmune encephalitis, sleep disorders have not been investigated in anti-glutamic acid decarboxylase (GAD65) associated neurological syndromes. METHODS: Six consecutive adult patients diagnosed with anti-GAD65-associated neurological syndromes (four with limbic encephalitis and two with stiff-person syndrome) and 12 healthy controls were enrolled. Participants underwent sleep interviews and sleep studies including night-time video-polysomnography, followed by five daytime multiple sleep latency tests (MSLTs, to assess propensity to fall asleep) and an 18 h bed rest polysomnography (to assess excessive sleep need). RESULTS: Patients reported the need for daily naps and that their cognition and quality of life were altered by sleepiness, but they had normal scores on the Epworth sleepiness scale. Compared with controls, sleep latencies during the MSLT were shorter in the patient group (median 5.8 min, interquartile range [IQR] 4.5, 6.0 vs. 17.7 min, IQR 16.3, 19.7, p = 0.001), and the arousal index was reduced (2.5/h, IQR 2.3, 3.0 vs. 22.3/h, IQR 13.8, 30.0, p = 0.002), although total sleep time was similar between groups (621 min, IQR 464, 651 vs. 542.5 min, IQR 499, 582, p = 0.51). Remarkably, all six patients had MSLT latencies ≤8 min, indicating severe sleepiness. No parasomnia or sleep-disordered breathing was detected. CONCLUSION: Central hypersomnia is a relevant characteristic of anti-GAD65-associated neurological syndromes.

Disentangling the complex landscape of sleep-wake disorders with data-driven phenotyping: A study of the Bernese center.

BACKGROUND AND PURPOSE: The diagnosis of sleep-wake disorders (SWDs) is challenging because of the existence of only few accurate biomarkers and the frequent coexistence of multiple SWDs and/or other comorbidities. The aim of this study was to assess in a large cohort of well-characterized SWD patients the potential of a data-driven approach for the identification of SWDs. METHODS: We included 6958 patients from the Bernese Sleep Registry and 300 variables/biomarkers including questionnaires, results of polysomnography/vigilance tests, and final clinical diagnoses. A pipeline, based on machine learning, was created to extract and cluster the clinical data. Our analysis was performed on three cohorts: patients with central disorders of hypersomnolence (CDHs), a full cohort of patients with SWDs, and a clean cohort without coexisting SWDs. RESULTS: A first analysis focused on the cohort of patients with CDHs and revealed four patient clusters: two clusters for narcolepsy type 1 (NT1) but not for narcolepsy type 2 or idiopathic hypersomnia. In the full cohort of SWDs, nine clusters were found: four contained patients with obstructive and central sleep apnea syndrome, one with NT1, and four with intermixed SWDs. In the cohort of patients without coexisting SWDs, an additional cluster of patients with chronic insomnia disorder was identified. CONCLUSIONS: This study confirms the existence of clear clusters of NT1 in CDHs, but mainly intermixed groups in the full spectrum of SWDs, with the exception of sleep apnea syndromes and NT1. New biomarkers are needed for better phenotyping and diagnosis of SWDs.

Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new-onset sleepiness in some post-COVID patients.

BACKGROUND AND PURPOSE: Infection with COVID-19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post-COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post-COVID syndrome using polysomnography. METHODS: Thirty-four patients with post-COVID syndrome and new-onset fatigue and sleepiness after a SARS-CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020). RESULTS: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long-term treatment of their OSAS and all reported discontinuation of daytime symptoms. CONCLUSIONS: Post-COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post-COVID syndrome.

Supplement use and its impact on daily life of cancer patients: a cross-sectional study.

PURPOSE: This cross-sectional study aimed to investigate the prevalence and characteristics of supplement usage among cancer patients and explore its potential associations with anxiety, excessive daytime sleepiness, and overall quality of life. METHODS: Cancer patients receiving specific care at Hôtel Dieu de France University Hospital, Beirut, were enrolled between April and June 2023. In face-to-face interviews, participants were asked to complete a questionnaire consisting of sociodemographic information, supplement usage details, and cancer-related variables. Three validated surveys (Epworth Sleepiness Scale, GAD-7, and EORTC-QLQ-C15-PAL) were employed to assess excessive daytime sleepiness, anxiety, and overall quality of life. Statistical analyses, including chi-square tests, t-tests, and multiple regression models, were conducted to examine associations between supplement use and other variables. RESULTS: A total of 202 participants were interviewed. Fifty-two percent reported regular use of supplements following their cancer diagnosis, with vitamin D being the most commonly used supplement. Using multivariate logistic regression, supplement use was associated with being female, having lower educational levels, having a longer duration since cancer diagnosis, and having a poor overall quality of life. The multivariate logistic regression showed no significant correlation between supplement use and excessive daytime sleepiness and anxiety. CONCLUSION: This study highlights a high prevalence of supplement usage among cancer patients in Lebanon, indicating a rising interest in alternative therapies aimed at enhancing quality of life. Larger prospective studies are needed to assess the relation between supplement intake and excessive daytime sleepiness and anxiety and establish clear guidelines pertaining to supplement use in cancer patients.

Evolution of Sleep Complaints in Myotonic Dystrophy Type 1: A 9-Year Longitudinal Study.

The objective was to characterize the progression of sleep complaints in 115 dystrophy type 1 (DM1) patients who filled out a sleep questionnaire twice at a 9-year interval. Daytime napping (22.1% vs. 34.5%, p < 0.05), early awakenings (11.4% vs 21.1%, p < 0.05), nonrestorative sleep (39.5% vs 51.8%, p < 0.05), stimulant use (7.0% vs 19.3%, p < 0.01), breathing cessation (10.7% vs 23.2%, p < 0.01), and nighttime urination (42.5% vs 54.9%, p < 0.05) increased between Time 1 and Time 2. Sleep-related complaints are prominent and augment rapidly in DM1 patients. Physicians need to better identify and treat them to help alleviate the burden they impose on patients and their caregivers.

Évolution des troubles du sommeil dans la dystrophie myotonique de type 1 : une étude longitudinale de 9 ans.L'objectif était de caractériser l'évolution des plaintes liées au sommeil chez 115 patients atteints de dystrophie myotonique de type 1 (DM1) ayant rempli un questionnaire sur le sommeil à deux reprises à 9 ans d'intervalle. La prévalence des siestes (22,1 % vs 34,5 %, p < 0,05), des réveils matinaux précoces (11,4 % vs 21,1 %, p < 0,05), du sommeil non réparateur (39,5 % vs 51,8 %, p < 0,05), de la consommation de stimulants (7,0 % vs 19,3 %, p < 0,01), des arrêts respiratoires (10,7 % vs 23,2 %, p < 0,01) et des mictions nocturnes (42,5 % vs 54,9 %, p < 0,05) a augmenté entre le temps 1 et le temps 2. Les plaintes liées au sommeil sont fréquentes et augmentent rapidement dans la DM1. Les médecins doivent mieux les identifier et les traiter pour aider à alléger le fardeau qu'ils imposent aux patients et à leurs aidants.

Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.

OBJECTIVE: This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. METHODS: Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3 T MRI scanner was used to acquire images in 35 of 77 PD patients. RESULTS: Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. CONCLUSIONS: This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment.

Genotype and sleep independently predict mental health in Rett syndrome: an observational study.

BACKGROUND: Rett syndrome is a genetically caused neurodevelopmental disorder associated with severe impairments and complex comorbidities. This study examined predictors of anxiety and depression in Rett syndrome, including genotype. METHODS: The International Rett Syndrome Database, InterRett, was the data source for this observational study. Associations between genotype, functional abilities, comorbidities, anxiety and depression were estimated with univariate and multivariate regression models. An additional regression model for anxiety included use of an anxiety medication as a predictor variable. RESULTS: The sample included 210 individuals aged 6-51 years of whom 54 (25.7%) were on psychotropic medication for anxiety or depression. Individuals with the p.Arg294* variant had the highest anxiety scores, as did those with insomnia or excessive daytime sleepiness, irrespective of anxiety medication use. Individuals with the p.Arg306Cys variant had the lowest depression scores, as did those with insomnia or excessive daytime sleepiness. CONCLUSION: Findings indicated that genotype and sleep have implications for mental health in Rett syndrome, suggesting that anticipatory guidance and proactive management of poor sleep could improve mental health. More research is needed to understand the effects of psychometric medications, which cannot be inferred from this cross-sectional study.

Patient-reported experience with hypoglossal nerve stimulation in the treatment of obstructive sleep apnea.

BACKGROUND: Breathing-synchronized hypoglossal nerve stimulation (HNS) is routinely used as an alternative treatment for patients with obstructive sleep apnea (OSA). Significant and clinically relevant improvements in disease severity and OSA symptoms such as daytime sleepiness as well as overall quality of life have been reported in randomized-controlled trials and large real-world cohort studies. However, so far, few data exist on patient-reported experience with the treatment. METHODS: A structured survey with 22 questions was constructed using five-level Likert scales (1 = no agreement, 5 = complete agreement) to evaluate patient experience with HNS and perception of the treatment in the domains "Overall experience with therapy," "Experience with treatment process," and "Side-effects from treatment." Additional data were collected on current symptom status, measured with Epworth sleepiness scale (ESS) questionnaire, and OSA disease history. Multiple linear regression analysis was conducted to test associations of medical variables and response behavior. Correlations between variables and domains, as well as individual items, were assessed using Spearman rank test. RESULTS: A total of 75 patients from Germany who were treated with breathing-synchronized HNS were enrolled (mean age 57.3 years, 78% male), and 71 questionnaires with complete data were included for analysis. Two-thirds of participants (67%) had a history of OSA history for 5 years or longer. Of all patients, 76% had normalized OSA symptoms at time of the study (ESS: 6.4 ± 5.0) and 98% reported using stimulation therapy every night. Regression analysis revealed an association of current symptoms measured with ESS and response behavior. Hence, patients with normalized daytime sleepiness reported significantly more positive experience across all domains assessed, compared to patients with residual daytime sleepiness. Overall, only 2% of participants reported side effects that made them reduce or discontinue stimulation therapy. The rate of reported side effects was associated with current symptom control under therapy. CONCLUSIONS: Overall patient-reported experience with breathing-synchronized HNS therapy was positive and high satisfaction with the treatment process was observed. Side effects occurred, but rarely affected subjective use of the therapy or satisfaction. Subjective experience and perception are influenced by residual daytime sleepiness with stimulation therapy.

Effects of mandibular advancement devices on the evolution of obstructive sleep apnea.

PURPOSE: Mandibular advancement devices (MADs) are a treatment for obstructive sleep apnea (OSA). Titration is a necessary component of proper fitting of MADs, yet little is known about what happens at each step of the titration. The objectives of this study were to determine the clinical and paraclinical evolution of OSA at every mm of MAD advancement. METHODS: Volunteers were fitted with MADs set to 50% of maximum advancement. MAD clinical and paraclinical results were recorded at every additional mm-titration, including apnea-hypopnea index (AHI), as well as symptoms of sleepiness and fatigue. RESULTS: In 20 volunteers with OSA, the MAD had a significant effect on every polygraphic parameter at the onset of use. The mean AHI with MAD fell by 15.2/h (p < 0.001). The mean Epworth Sleepiness Score and Pichot Fatigue questionnaire with MAD fell by 2.0 (p = 0.0687) and 2.4 (p = 0.1073) respectively. There was no proportionality between clinical gains (drowsiness and fatigue) and AHI improvements. CONCLUSIONS: MADs led to a significant improvement in AHI and other polygraphic parameters from the onset of use. The decrease of clinical symptoms (drowsiness and fatigue) was more complex to interpret because of the small decreases observed. The absence of concordance between AHI improvement and clinical symptoms was nevertheless objectively quantified and symptoms were alleviated with advancements. The findings suggest that it may be appropriate to use clinical symptoms as a main aim of titration, since the improvement in AHI is reached at the onset of MAD use.

Prevalence and associated factors of excessive daytime sleepiness in rural older adults: a population-based study.

OBJECTIVE: To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults. METHODS: We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10. RESULTS: This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95-0.99), female sex (0.53; 0.36-0.77), hypertension (0.68; 0.54-0.85), depressive symptoms (2.68; 2.07-3.46), high OSA risk (2.11; 1.69-2.63), and poor sleep quality (2.12; 1.60-2.82). CONCLUSION: EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS.

Excessive daytime sleepiness in young and middle-aged Chinese adults with obstructive sleep apnea: implications for cognitive dysfunction.

OBJECTIVE: The objective of this study was to investigate the effects of excessive daytime sleepiness (EDS) on cognitive function among Chinese young and middle-aged Chinese patients with obstructive sleep apnea (OSA). METHODS: Chinese adults struggling from moderate to severe OSA with apnea-hypopnea index (AHI) ≥ 15 events per hour and adults with primary snoring and mild OSA (AHI < 15 events per hour) were included in the study. The Epworth Sleepiness Scale measured hypersomnia, and cognitive function was assessed using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). RESULTS: In comparison to the primary snoring and mild OSA group (n=635), the moderate to severe OSA group (n=1423) tended to be older men with higher scores on the Epworth Sleepiness Scale (ESS), as well as higher levels of oxygen desaturation (ODI) and a higher body mass index (BMI). Patients with moderate to severe OSA had fewer years of education, lower minimum arterial oxygen saturation (min-SaO2), and more severe sleep disturbances, such as decreased slow wave sleep (SWS) and rapid eye movement (REM) and increased non-REM stages (N1 and N2). Comorbid conditions such as hypertension and diabetes mellitus were more common in these patients (P < 0.01 and P < 0.05, accordingly). Only the delayed recall scores were statistically lower in the moderate to severe OSA group than the primary snoring and mild OSA group (P < 0.05). The main factor associated with delayed recall was the ESS score rather than age or years of education among moderate-severe OSA patients ≤ 40 years of age (P < 0.05). After controlling for potential confounding factors such as age, gender, BMI, education, hypertension, diabetes, sleep stages (SWS and REM), minimum arterial oxygen saturation (min-SaO2), oxygen ODI, and AHI, there was a negative correlation between the Epworth Sleepiness Scale (ESS) score and the delayed recall scores. CONCLUSION: Patients with moderate to severe OSA had cognitive dysfunction, particularly impairment of delayed recall. Excessive daytime sleepiness (EDS) was significantly associated with cognitive dysfunction in young and middle-aged patients with OSA.

Poor sleep quality and its associated neurocognitive function in children with obesity with or without obstructive sleep apnea.

OBJECTIVE: To evaluate the associations of OSA severity, snoring symptoms, subjective sleep quality, and daytime sleepiness with executive functioning and behaviors in children with obesity. METHODS: This was a cross-sectional study of children aged 8-18 years with obesity and symptoms suggestive of OSA. All participants underwent an overnight polysomnography and completed a set of questionnaires to assess their sleep-related breathing disordered (SRBD) symptoms [Pediatric Sleep Questionnaire (SRBD-PSQ)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], executive function [Behavior Rating Inventory of Executive Function (BRIEF)], and inattention and hyperactivity symptoms (Conners-3 Parent Short Form). RESULTS: A total of 85 children (62% male, mean age: 13.9 ± 3.0 years) were included in this analysis, of whom 36, 16, and 33 were categorized into the non-OSA (obstructive apnea hypopnea index, OAHI < 1.5/h), mild OSA (OAHI 1.5-5/h), and moderate-severe OSA (OAHI ≥ 5/h) groups, respectively. Of 85 participants, 27 (32%) were classified with poor sleep quality (PSQI composite score ≥ 8). From multiple linear regression analyses, poor sleep quality and sleepiness were both independently associated with higher BRIEF behavioral regulation T-score, metacognition T-score, and global executive composite T-score in the fully adjusted model. In addition, poor sleep quality was also independently associated with higher Conners-3 inattention and executive functioning T-scores, while greater sleepiness was also associated with a higher learning problem T-score. The presence of OSA and snoring were not associated with any cognitive outcomes. CONCLUSIONS: Subjective sleep quality and daytime sleepiness, but not OSA severity and snoring symptoms, were independently associated with executive functioning and behavioral problems in children with obesity.