SCORE2-Older Persons (SCORE2-OP): Validation and Added Value of Excessive Daytime Sleepiness in a French Cohort.

Background: Cardiovascular diseases are the leading cause of death worldwide, particularly in older adults. While the Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP) model estimates 10-year cardiovascular risk in this population, its validation in general European cohorts remains limited. Given growing relationships between sleep disturbances and cardiovascular risk, we aimed to validate SCORE2-OP in a French cohort and assess the incremental value of excessive daytime sleepiness (EDS).

Once-Nightly Sodium Oxybate Meets American Academy of Sleep Medicine Criteria for Treatment of Narcolepsy.

Data from the REST-ON trial were not available before the 2021 American Academy of Sleep Medicine (AASM) clinical practice guideline update, which included a literature review through August 2020. This post hoc analysis from REST-ON assessed participants who achieved clinically significant improvements on individual AASM clinical significance thresholds (CSTs). Composites of the coprimary endpoints and a secondary endpoint were also analysed.

Lucid Dreaming: Not Just Awareness, but Agency.

During lucid dreaming (LD), dreamers are aware that they are dreaming and may be able to influence the oneiric content. There has been recent debate about the relative importance of the ability to influence the dream and having agency over the pure awareness of dreaming. To underline this, we examined the associations of lucid dreams without agency (LD-Ag) and lucid dreams with agency (LD + Ag) to sleep and mental health problems and long COVID during the pandemic.

Age at Onset and Delays in Diagnosis of Central Disorders of Hypersomnolence Over the Past 30 Years.

Patients with narcolepsy type 1 (NT1), type 2 (NT2), idiopathic hypersomnia (IH) usually suffer from symptoms for years, even decades, before being diagnosed. We aimed to assess age at onset, age at diagnosis and changes in the diagnostic delays of these patients from 1990 to 2020 in a single centre. Age at onset, age at diagnosis and diagnostic delays of patients with NT1, NT2 and IH were collected at the Reference Narcolepsy Centre, Montpellier-France.

Sleep Disruption and Atrial Fibrillation: Evidence, Mechanisms and Clinical Implications.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, with its incidence rising due to aging populations, obesity, and advancements in diagnostic modalities. The interplay between sleep disorders and AF is increasingly recognized, with obstructive sleep apnea (OSA) serving as a well-established risk factor. However, emerging evidence implicates additional sleep disturbances-including central sleep apnea, insomnia, and restless legs syndrome-in AF pathogenesis and progression.

Restless Legs Syndrome, Periodic Leg Movements, Hypertension and Cardiovascular Diseases.

Restless legs syndrome (RLS) is a frequent sleep-related sensorimotor disorder defined by an urge to move the legs in the evening while resting. Severe RLS symptoms can negatively impact sleep, mood, and quality of life. Periodic leg movements during sleep and wakefulness are found in 60% to 80% of patients with RLS.

16-mer hypocretin-1/orexin-A in cerebrospinal fluid to diagnose narcolepsy.

Study Objectives: Cerebrospinal fluid (CSF) hypocretin-1/orexin-A quantification via radioimmunoassay (RIA) is used for diagnosing narcolepsy type 1(NT1), but its limitations require alternative methods. Using liquid chromatography-mass spectrometry (LC-MS), this study aimed to 1/fully characterize CSF orexin-A fragments detected by the gold standard RIA method, and 2/assess diagnostic relevance of measuring the most prevalent fragment, a 16-mer, in patients with NT1, narcolepsy type 2(NT2), idiopathic hypersomnia (IH) and non-specified hypersomnolence (NSH).

Methods: CSF samples were analyzed using RIA and LC-MS in patients with hypersomnolence disorders evaluated at the French Narcolepsy National Reference Center.

Management of Insomnia Complaints by Non-Sleep Specialist Physicians: A French DELPHI Consensus.

Insomnia is the most prevalent sleep disorder and a major public health concern, affecting chronically up to 19% of the adult population in France. Despite its significant impact on quality of life, mental health, and cardiometabolic disease, insomnia disorder remains underdiagnosed and inadequately managed. General Practitioners (GPs) play a pivotal role in addressing insomnia complaints but often face constraints, such as limited consultation time and a lack of specialised training.

Systematic Assessment of Dysexecutive Syndrome, Hypersomnolence and Dysautonomia in Kleine-Levin Syndrome.

Background: Kleine-Levin Syndrome (KLS) is a neurological disorder of unknown pathophysiology. It is characterized by relapsing-remitting episodes of hypersomnia, with cognitive symptoms and behavioral disturbances. The diagnosis relies on clinical criteria, which require further standardization.

Weight changes during treatment with low-sodium oxybate in two phase 3 clinical studies in participants with narcolepsy or idiopathic hypersomnia.

Objective: Low-sodium oxybate (LXB) is approved in the United States for treating cataplexy or excessive daytime sleepiness in patients aged ≥7 years with narcolepsy and idiopathic hypersomnia in adults. This post hoc analysis evaluated LXB effects on weight in patients with narcolepsy or idiopathic hypersomnia from two phase 3 studies.

Methods: Adults with narcolepsy with cataplexy or idiopathic hypersomnia began LXB treatment during open-label titration (10-14 weeks), followed by 2-week stable-dose periods (SDP).

Characteristics of Maintenance of Wakefulness Test (MWT) in drug-naïve patients with narcolepsy type 1 and type 2, and relationship with other measures of sleepiness.

Study Objectives: We aimed to describe the characteristics of standard maintenance of wakefulness test (MWT), outside of clinical trials, in a sample of drug-naïve patients with narcolepsy type 1 (NT1) and type 2 (NT2).

Methods: Consecutive drug-naïve patients with narcolepsy underwent two days of continuous PSG recording, the multiple sleep latency test (MSLT), then night-PSG and, on the following day, MWT. MWT results were correlated with MSLT and Epworth Sleepiness Scale (ESS).

Present and Future of Central Disorders of Hypersomnolence.

Central disorders of hypersomnolence (CDH) are rare neurological conditions lumped by excessive daytime sleepiness (EDS) as primary complaint mostly arising at young age, including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kleine-Levin syndrome (KLS). Advances in clinical and translational research have deepened our understanding of NT1, particularly the loss of hypothalamic hypocretin/orexin-producing neurons, establishing hypocretin deficiency as a reliable disease specific biomarker, although the exact mechanisms of neuronal loss remain unknown. Conversely, the pathophysiological mechanisms underlying NT2, IH, and KLS are still poorly understood, as well as their natural course.

Shedding light on microsleep episodes for comprehensive sleepiness assessment: a narrative review.

Excessive daytime sleepiness is a consistent and common symptom in sleep medicine. It represents a major public health problem due to its association with significant impairments in quality of life, work productivity, and driving ability. Objective clinical tests for assessing excessive daytime sleepiness follow the universal American academy of sleep medicine scoring classification, which overlooks short intrusions of sleep during wake states, known as microsleep episodes.

Sleep overestimation differentiates between participants with suspected idiopathic hypersomnia.

Study Objectives: To investigate sleep perception during a 32-hour continuous bedrest polysomnography in patients with idiopathic hypersomnia (IH), non-specified hypersomnia (NSH) and healthy controls (HC).

Methods: Patients with suspected IH, and HC (n=14) underwent a regular polysomnography, a modified multiple sleep latency test (MSLT) and a 32-hour bedrest protocol, from 11PM till 7AM the day after, without circadian synchronizers. Patients were diagnosed with IH with long-sleep-time (IH-LST, n=72) if they had a positive bedrest (sleep duration≥19h), without LST (IH-nLST, n=10, sleep duration<19h, MSLT mean sleep latency≤8min), or NSH otherwise (n=26).

Unraveling the pathophysiology of narcolepsy type 1 through hypothesis-driven and hypothesis-generating approaches.

Narcolepsy type 1 (NT1) is a chronic orphan neurological sleep disorder characterized by the loss of hypocretin-producing neurons in the lateral hypothalamus, which play a crucial role in wakefulness. Given the genetic association with the HLA-DQB1 * 06:02 allele and environmental links with the 2009 influenza pandemic, many lines of evidence point towards an immune mechanism, notably autoimmunity, underlying the disease pathophysiology. Autoreactive T cells are found in the blood of NT1 patients, and mouse models demonstrate their migratory capacity and contribution in the selective destruction of hypocretin-producing neurons.

Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1.

Background: Narcolepsy type 1 is a disorder of hypersomnolence caused by a loss of orexin neurons, which results in low orexin levels in the brain.

Methods: In this phase 2, randomized, placebo-controlled trial, participants with narcolepsy type 1 received once- or twice-daily oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (MWT) (range, 0 to 40 minutes; normal, ≥20).

Efficacy and Safety of Sodium Oxybate in Adults With Idiopathic Hypersomnia: A Randomized Controlled Trial.

Background And Objectives: Idiopathic hypersomnia (IH) is a rare central disorder of hypersomnolence characterized by excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia. Low-sodium oxybate is the sole Food and Drug Administration-approved treatment for IH. Objective measures of nighttime sleep and daytime sleepiness are lacking with oxybates in IH.

Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults.

Introduction: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.

Methods: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images.

LRRK2 rare-variant per-domain genetic burden in Parkinson's Disease: association confined to the kinase domain.

LRRK2 variants are key genetic risk factors for Parkinson's Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: P = 1.

Effect of daridorexant on nighttime wakefulness and next-morning sleepiness: assessing the transition from night to day in insomnia disorder.

Objective/background: Reducing wakefulness throughout the night without next-day residual effects are essential characteristics for drugs for chronic insomnia disorder. In Phase 3 trials, daridorexant significantly reduced polysomnography-determined wake after sleep onset (WASO) versus placebo, and rates of daytime somnolence were similar to placebo. This analysis examines the effect of daridorexant on WASO in each 2-h quarter (Q) of the night (8-h recording), and on next-morning sleepiness, daytime alertness and ability to function (assessed daily using visual analog scales [VAS]), and the correlation between these night and day assessments.

Prevalence Rates of Frequent Dream Recall and Nightmares by Age, Gender and Sleep Duration in 16 Countries.

The present study aimed to describe the prevalence rates of frequent (i.e., at least weekly) dream recall and nightmares with consideration for differences in age, gender and sleep duration in 16 countries using equivalent assessment methods.

Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).

To study the impact of the COVID-19 pandemic on sleep and circadian rhythms-two fundamental pillars for health-the collaboration International COVID-19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questionnaire to cover changes in sleep and sleep disorders, as well as physical and mental health.

Sex effect on disease characteristics in patients with narcolepsy type 1.

Study Objectives: Narcolepsy type 1 (NT1) is a rare sleep disorder caused by orexin/hypocretin (Hcrt-1) deficiency, equally prevalent in women and men. Sex differences have been reported in animal models, particularly regarding cataplexy. Whether these differences can be transposed to humans remains unclear.

Insomnia, early and late rising are associated with small hippocampal volume and large white matter hyperintensity burden.

Background: Sleep disturbances have been associated with an increased risk of dementia. The mechanisms remain unclear, although neurodegenerative and vascular pathways are potentially involved. Hence, our study aims to investigate the relationships between several clinical sleep and polysomnographic features and volumes of hippocampus (indicative of neurodegeneration) and white matter hyperintensities (WMH) (reflecting vascular processes).