Sleep Onset Insomnia Research Articles

0821 Narcolepsy after West Nile Virus Meningoencephalitis infection

Abstract Introduction Narcolepsy is a sleep disorder characterized by hypersomnia and inappropriate intrusion of REM sleep into wakefulness. Etiology is heterogeneous, and is broadly classified into Narcolepsy Type 1 and Type 2. There is growing evidence that the pathogenesis in many cases have a post-infectious autoimmune basis. We present the case of a patient seen in our sleep clinic who was eventually diagnosed with Narcolepsy type 2 following West Nile Virus (WNV) Meningoencephalitis. Report of Cases: · The patient is a 44 year old Hispanic woman who had no prior sleep difficulties before 2013, when she was diagnosed with WNV meningitis. Lumbar puncture results from the time of infection are not available, as this evaluation occurred in the Dominican Republic. Subsequent lumbar punctures have shown the presence of anti-WNV IgG antibodies in her CSF. MRI and MRA brain were unremarkable. · She also has a history of migraine, fibromyalgia, depression, and adrenal insufficiency. · She presented with sleep complaints, including sleep onset insomnia, symptoms of sleep disordered breathing, and excessive daytime sleepiness. · She underwent home sleep apnea test in 12/2020 which revealed mild obstructive sleep apnea. Overall AHI was 7.9/hour without significant hypoxemia. She was subsequently started on CPAP therapy with good adherence, but she continued to have significant daytime sleepiness, notably with an Epworth Sleepiness Scale score of 21/24. · She subsequently underwent overnight polysomnogram and multiple sleep latency test in our sleep laboratory. · Overnight PSG confirmed mild obstructive sleep apnea (AHI 12.0) along with short REM latency (10.5 minutes). Next day MSLT showed mean sleep latency of 2.3 minutes, for 5 attended naps, with 2 SOREMPs, which was diagnostic of Narcolepsy type 2. Conclusion This case demonstrates the onset of narcolepsy after WNV meningoencephalitis. Support (If Any)

Lemborexant, an orexin receptor antagonist sedative-hypnotic: Is it useful for insomnia in psychiatric disorders?

Lemborexant, an orexin receptor antagonist similar to suvorexant, has been approved for the treatment of sleep onset and/or maintenance insomnia. Lemborexant is reviewed and compare to suvorexant from a psychiatric perspective. Rapidly absorbed (peak 1-3h), lemborexant has a half-life of 17-19h (suvorexant half-life 12h). It is metabolized by CYP3A4/5, with no significant effects of age, sex or weight. Trials for insomnia indicate sustained efficacy beyond 6months. Lemborexant has not been trialled in major psychiatric disorders. Commenced at 5mg, lemborexant can then be increased to 10mg, taken at least 7h before planned awakening. Adverse effects are higher at 10mg: somnolence occurs in about 10% while headache and nightmares affect 2-5%, approximately similar to 40mg suvorexant (recommended suvorexant dose 20mg). Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms, complex sleep behaviours and emergence of depression/suicidal ideation can occur. Neither tolerance to sedation nor withdrawal effects on discontinuation have been observed. Whether the differences between lemborexant and suvorexant are clinically relevant is unclear. Like suvorexant, lemborexant appears to be effective in longer-term use for insomnia, but until efficacy and safety are adequately investigated in major mental disorders, clinicians need to monitor patient experience closely.

Efficiency moderates the relationship between sleep-onset insomnia and resting-state electroencephalogram microstate.

Overactivation of the salience network (SN) causes hyperarousal in insomnia patients and is associated with sleep-onset insomnia (SOI). Resting-state microstate 3 (RS-MS3) duration is closely related to SN overactivation. However, whether RS-MS3 duration is a biomarker for SOI has not yet been reported in the literature. In addition, SN activity is also associated with efficiency. However, it is not clear whether there are individual differences in the neural mechanisms of SOI in different efficiency groups. Considering that RS-MS3 duration characterizes the stability and persistent activation of the SN in the resting state, the current study investigated the link between SOI measured by sleep latency of Pittsburg Sleep Quality Index (PSQI), efficiency measured by Kirton Adaption-Innovation Inventory (KAI), and RS-MS3 in a Chinese healthy (subclinical) student population, using electroencephalography (EEG) microstate analysis. We found that RS-MS3 duration was positively correlated with sleep latency and efficiency. The interaction between sleep latency and efficiency was significant. Simple slope analysis showed that high sleep latency was positively correlated with longer RS-MS3 duration in participants with higher efficiency scores. This correlation did not exist in participants with low efficiency scores. RS-MS3 duration may serve as a biomarker for SOI. There is heterogeneity in the relationship between SOI and RS-MS3 duration between individuals with high and low efficiency.

Approches thérapeutiques des troubles du sommeil et des rythmes chez l’enfant avec TSA

Sleep disturbances are extremely common (40–86%) in children and adolescents, especially those with autism spectrum disorders (ASD) and are often among the first symptoms identified by parents at a very early stage of their child's development. These abnormalities are among the main parental concerns when having a child with ASD and have a significant impact on the quality of life of patients, their parents, and more broadly their siblings. Sleep disorders are essentially abnormalities of the sleep-wake rhythm – primarily sleep onset insomnia or nocturnal awakenings (with difficulty falling back to sleep). These disturbances can be accompanied by other sleep disorders, requiring notably a systematic elimination of the presence of a sleep apnea or restless legs syndrome – to ensure a personalized and efficient therapeutic approach. Physiologically, the determinants of these sleep disorders are poorly understood, even though several studies point to a significant decrease in melatonin synthesis in people with ASD. Melatonin is a hormone that facilitates falling asleep and maintaining sleep and is also involved in the endogenous synchronization of internal biological clocks. However, the causal factors of this decrease in melatonin synthesis are largely unknown, involving to a small extent the genes involved in melatonin synthesis pathway. The treatment of sleep disorders is relatively systematic: after eliminating other specific sleep disorders associated with the complaint of insomnia, as well as other possible associated comorbidities (such as seizures), a global and graduated therapeutic approach must be put in place. This treatment will be non-pharmacological as a first line, then pharmacological as a second line. A number of non-pharmacological treatment strategies for sleep disorders in typically developing children and adolescents, as well as those with ASD, have been shown to be effective. This treatment requires a combination of: 1) parental education to promote sleep development; 2) setting up bedtime rituals adapted to the child's age and particularities; 3) specific behavioral strategies including bedtime fading, gradual extinction and positive reinforcement of adapted behaviors. It is very essential that the parents are accompanied throughout this therapy. Sleep hygiene and behavioral care must also take into consideration the important role of the zeitgebers of sleep-wake rhythms, i.e. the external environmental factors involved in the synchronization of the biological clocks: regular exposure to light at adapted times, regular meal and wake-up times, social activities and times for going to school. The evidence for the effectiveness of behavioral interventions in the treatment of behavioral insomnia in the typical developmental child is strong, since 94% of children show clinically significant improvements in nighttime sleepiness and waking. By contrast, only about 25% of children with ASD are improved by an approach combining sleep hygiene and behavioral therapy. Melatonin has a special and prominent place in the drug management of sleep disorders associated with ASD. Several clinical trials have shown that melatonin is effective in treating sleep disorders in patients with ASD. This work led to the European Medicines Agency (EMA) granting marketing authorization in September 2018 for a sustained-release paediatric melatonin molecule (Slenyto®). This synthetic molecule is a prolonged release melatonin (PRM) which mimics the physiological pharmacokinetic and secretory characteristics of endogenous melatonin, having a very short blood half-life and prolonged secretion for several hours during the night. A recent study evaluated the efficacy and safety of pediatric PRM (mini-tablets) in 125 children, aged 2 to 17.5 years with mainly ASD. After 15 days on placebo, the children were randomized into two parallel groups, PRM or placebo in a double-blind design for 13 weeks. At endpoint, total sleep time was increased by an average of 57.5 minutes on PRM and only 9.14 minutes on placebo (P=0.034). This difference between the two groups was already significant after three weeks of treatment (P=0.006). Sleep latency was also improved in the PRM group (−39.6 minutes) compared to placebo (−12.51 minutes) (P=0.01). Consolidated sleep duration (uninterrupted by awakenings) was improved by 77.9 minutes for the PRM group and only 25.4 minutes for the placebo group (P<0.001). PRM was well tolerated, the most frequent side effects being headache and daytime drowsiness at the same level with PRM or placebo. In addition, the acceptability by the children for swallowing the mini-tablets was excellent (100% compliance). The efficacy and tolerability of PRM was maintained over the medium and long term in the open phase, over a total study duration of 2 years.

Intensive sleep retraining treatment for insomnia administered by smartphone in the home: an uncontrolled pilot study.

Intensive sleep retraining (ISR) is a behavioral treatment that involves a patient falling asleep repeatedly over 1 treatment session (< 24 hours in duration) to treat sleep-onset insomnia. ISR relies on high homeostatic sleep and circadian rhythm drives to facilitate rapid sleep onsets overnight. The high cost and inaccessibility of laboratory-based ISR is a significant practical barrier to treatment uptake. Smartphone-delivered ISR offers a significantly more affordable, flexible, and efficient method to treat chronic insomnia. The present study is the first trial of ISR administered via smartphone in the home environment. Smartphone-delivered ISR was investigated with 12 individuals with chronic insomnia (9 women, 3 men, aged 49.75 ± 7.71 years) using a single-group, repeated-measures, case-replication series design. Participants received a single overnight session of home-based ISR treatment administered by smartphone. Sleep onset trials started at 23:00 and concluded after 40 trials or at 11:00 the following morning, whichever occurred first. Sleep diary and psychological variables associated with insomnia were measured at pretreatment, post-treatment, and 4- and 7-week follow-up. Significant improvements with moderate to strong effects (d = 0.59-1.94) were indicated for sleep-onset latency, sleep efficiency, insomnia symptom severity, sleep self-efficacy, anticipatory sleep anxiety, dysfunctional beliefs about sleep, and daytime fatigue and functioning compared to baseline. Therapeutic benefits were largely maintained at the 7-week follow up. This pilot study suggests that ISR may be feasibly administered via smartphone in the home. With fewer trials and a shorter treatment session, smartphone-delivered ISR seemed to achieve similar outcomes to the earlier laboratory-based ISR procedure. Randomized controlled trials are warranted to investigate the efficacy of smartphone-administered ISR. Mair A, Scott H, Lack L. Intensive sleep retraining treatment for insomnia administered by smartphone in the home: an uncontrolled pilot study. J Clin Sleep Med. 2022;18(6):1515-1522.

Sleep Disorders and Future Diagnosis of Parkinsonism: A Prospective Study Using the Canadian Longitudinal Study on Aging.

Earlier detection of parkinsonism, specifically during its prodromal stage, may be key to preventing its progression. Previous studies have produced contradictory results on the association between sleep symptoms and prodromal parkinsonism. We conducted a prospective study within the Canadian Longitudinal Study on Aging (CLSA) to determine whether self-reported symptoms of insomnia, somnolence, apnea, and restless legs syndrome predate the diagnosis of parkinsonism after three years of follow-up. At baseline, amongst other information, participants completed a questionnaire for difficulty initiating or maintaining sleep, daytime somnolence, snoring or stopping breathing during sleep, and symptoms of restless legs syndrome. After 3 years of follow-up, baseline responses from participants who self-reported a new diagnosis of parkinsonism (cases) were compared to those who did not (controls). For each case, 10 controls were individually matched by age, sex, education, BMI, caffeine, smoking, and alcohol. Binary unconditional logistic regression models were used to estimate the association between sleep symptoms and new-onset parkinsonism, adjusting for age, sex, education, BMI, smoking, alcohol, and caffeine. We identified 58 incident-parkinsonism cases and 580 matched controls (65.5%male, mean age = 69.60, SD = 8.0). Baseline symptoms of sleep-onset insomnia (12.1%vs. 13.0%, Adjusted OR[95%CI] = 0.87[0.32,2.33]), sleep-maintenance insomnia (24.1%vs. 20.2%, AOR = 1.01[0.46,2.20]), daytime somnolence (8.6%vs. 7.4%, AOR = 1.11[0.37,3.39]), obstructive sleep apnea (27.3%vs. 26.2%, AOR = 0.84[0.40,1.79]), and restless leg syndrome (20.6%vs. 9.9%, AOR = 1.34[0.42,4.25]) were similar among those who developed parkinsonism and those who did not. Symptoms of insomnia, somnolence, apnea, and restless legs did not predate a new diagnosis of parkinsonism over 3 years.

The Association Between Self-Reported Screen Time, Social Media Addiction, and Sleep Among Norwegian University Students.

The aim of this study was to assess the relationship between daily screen time and sleep, evening screen time and sleep, and between social media addiction and sleep in a student population. This cross-sectional study is based on data from a national survey of all college and university students in Norway (the SHoT2018 study; n = 49,051). The sleep outcomes were sleep duration, sleep onset latency, sleep efficiency, and insomnia operationalized according to formal DSM-5 criteria. The results show a strong negative association between time spent on screen-based devices and sleep quality and quantity, and where screen use in bed had more consistent negative associations with sleep. Furthermore, there were higher rates of insomnia among those with higher levels of addiction, and curvilinear relationships with sleep duration, sleep onset latency, and sleep efficiency. Those with higher levels of addiction also had more evening screen time. The findings suggest that screen use plays an important role in students' sleep quantity and quality, where evening screen time has a stronger relationship with sleep compared to total daily screen time. The results also suggest a role of social media addiction, and addictive social media use may be a target for intervention in order to reduce evening screen time.

Early objective adherence to hypoglossal nerve stimulation therapy.

To assess early adherence to therapy with hypoglossal nerve stimulation therapy. This is a prospective study of consecutive patients with moderate to severe obstructive sleep apnea who underwent implantation of hypoglossal nerve stimulation therapy within a single academic practice and attended a follow-up appointment after greater than 30 days of therapy use. Objective adherence data were extracted from an objective monitoring database and compared to patient characteristics. The study population was 79 participants who were 29.1% female with a mean age of 58.7 ± 12.8 years old, body mass index of 28.9 ± 3.4 kg/m2, and baseline apnea-hypopnea index of 33.8 ± 17.6 events/h. In the first 7 days after device activation, average use was 7.8 h/night, with 91.9% of nights with greater than 4 hours of therapy use and an average of 0.2 pauses in therapy per night. These figures remained stable after 30 days of use: 7.7 h/night, 91.0% of nights longer than 4 hours, and 0.3 pauses per night. Objective evidence of difficulty with acclimatization was associated with age less than 60 years (odds ratio 2.8, 95% confidence interval 1.1-7.1, P = .03) and a history of prior upper airway surgery (3.9, 1.2-11.9, P = .015). Insomnia was present in 31 patients and was not associated with objective evidence of difficulty tolerating therapy. Early adherence to hypoglossal nerve stimulation is excellent (92.4% >4 hours on >70% of nights), suggesting that the acclimatization period is straightforward in most. Younger age and a history of prior upper airway surgery appear to be associated with an increased risk of difficulty with acclimatization. Huyett P. Early objective adherence to hypoglossal nerve stimulation therapy. J Clin Sleep Med. 2022;18(2):631-636.

Investigating racing thoughts in insomnia: A neglected piece of the mood-sleep puzzle?

BackgroundCognitive arousal is thought to play a key role in insomnia disorder. However, although patients frequently complain about racing thoughts appearing at bedtime, studies have considered ‘cognitive arousal’ as a synonym of rumination and worry, but not as racing thoughts per se. The latter have been mainly linked to hypomanic/manic episodes of bipolar disorder (BD). Here we aimed at investigating self-reported racing thoughts in insomnia disorder, and their specific contribution to insomnia severity, as compared to worry and rumination. Methods72 adults with insomnia disorder, 49 patients with BD in a hypomanic episode and 99 healthy individuals completed the Racing and Crowded Thoughts Questionnaire (RCTQ). Mood symptoms were assessed in patients with insomnia disorder. ResultsRCTQ scores were overall higher in insomnia disorder, especially in sleep-onset insomnia, compared to the hypomanic and healthy groups. Moreover, racing thoughts showed an increase in the evening and at bedtime in sleep-onset insomnia. Importantly, racing thoughts at bedtime, but not rumination and worry, were associated with insomnia severity. DiscussionOur results are the first to show that racing thoughts is a transdiagnostic symptom in mood and sleep disorders. Racing thoughts, not only rumination and worry, might contribute to the maintenance of sleep difficulties in insomnia.Clinical trials' registration number: NCT04752254

Treatment of insomnia - effect of trazodone and hypnotics on sleep.

Sedative antidepressants are commonly used drugs in the treatment of insomnia. However, some recommendations claim that only hypnotics have been proven effective in the treatment of sleep initiation and maintenance disorders. The aim of this article is to compare the effect of hypnotics and trazodone on sleep, and to analyse the evidence for the use of trazodone in the treatment of insomnia. Three studies investigated the effects of trazodone on sleep in primary insomnia, 5 studies on insomnia in the course of affective disorders and 6 studies on insomnia in other indications (PTSD, Alzheimer's disease, alcohol and opiate dependence, somatoform disorder, and insomnia during pregnancy). In the treatment of insomnia, trazodone is less effective than hypnotics in the treatment of sleep onset insomnia (i.e., disorders of falling asleep). For this indication it needs to be administered earlier than hypnotics, at least 1 hour before bedtime. It is, however, very effective in the treatment of sleep-maintenance insomnia, especially in patients with comorbid mental disorders or patients treated with activating antidepressants. Hypnotics and trazodone have the opposite effect on deep sleep. Trazodone increases the duration of deep sleep, which is associated with better sleep quality as assessed by patients. In contrast, hypnotics decrease slow-wave activityin sleep EEG, which is the biomarker of deep sleep. The main mechanism through which trazodone promotes sleep is its antagonistic effect on 5-HT2 serotonin receptors, while hypnotics are agonists of gamma-aminobutyric acid GABAA receptors, and other sedative antidepressants block H1 histamine receptors. This is associated with a low risk of weight gain, which is rare with trazodone treatment.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. Emens JS, St Hilaire MA, Klerman EB, etal. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Prevalence of chronic insomnia in patients with obstructive sleep apnea.

Objectives:To investigate the prevalence of and factors associated with chronic insomnia and obstructive sleep apnea (CIOSA) comorbidity in obstructive sleep apnea (OSA) patients.Methods:Between March 2014 and March 2015, we conducted a prospective, cross-sectional study of 238 adults diagnosed with OSA according to polysomnography and International Classification of Sleep Disorders-Third Edition criteria.Results:The prevalence of CIOSA was 29%. There was a trend towards older age in the CIOSA group. Sex was not associated with CIOSA. Sleep-maintenance and sleep-onset insomnia predominated in the sample. Beck’s depression and anxiety inventory scores were higher in the CIOSA group. Both depression and anxiety symptoms were associated with CIOSA. The arousal and apnea-hypopnea indices were lower in the CIOSA group. CIOSA was also associated with age ≥ 60 years and current tobacco use. Severe OSA and alcohol use were negatively associated with CIOSA.Conclusions:Chronic insomnia is prevalent among OSA patients. Our study highlights the need for detailed evaluation of patients with sleep breathing disorders to diagnose other important sleep and mood disorders (such as depression and anxiety), given their frequent association.

Insomnia symptom subtypes and manifestations of prodromal neurodegeneration: a population-based study in the Canadian Longitudinal Study on Aging.

To identify the association between insomnia symptoms and signs of prodromal neurodegeneration, including an analysis of potential differences between sleep-onset and sleep-maintenance insomnia. We included those aged 45-85 years, living in 1 of 10 Canadian provinces between 2012 and 2015 (at the baseline), recruited via 3 population-based sampling methods. Insomnia symptoms were assessed using questions adapted/modified from the Pittsburgh Sleep Quality Index. A panel of potential prodromal neurodegenerative markers including self-reported symptoms and objective gait motor, cognitive, and autonomic variables were assessed cross sectionally. We compared those who endorsed insomnia symptoms ≥ 3 times per week to controls, adjusting for age, sex, and education via logistic regression. Overall, 2,051/30,097 people screened positive for sleep-onset insomnia alone and 4,333 for sleep-maintenance insomnia alone, while 2,371 endorsed both subtypes. On objective gait tests, participants with sleep-onset insomnia, but not sleep-maintenance insomnia, had worse balance (odds ratio [OR] = 1.33, 95% confidence interval = [1.16, 1.52]) and slower gait speed (OR = 1.52 [1.34, 1.73]). Although participants with any insomnia subtype endorsed more motor symptoms, these were more severe in those with sleep-onset insomnia (OR onset vs maintenance = 1.13 [1.07, 1.18]). On objective cognitive tests, those with sleep-maintenance insomnia scored normally. However, participants with sleep-onset insomnia performed worse on tests of verbal fluency (OR = 1.24 [1.06, 1.43]), immediate memory (OR = 1.23 [1.08, 1.41]), and prospective memory task (OR = 1.29 [1.11, 1.50]). The sleep-onset insomnia group also had lower heart rate variability (OR = 1.23 [1.07, 1.43]). Secondary analyses found generally similar results in young vs older age of insomnia development. Compared to maintenance insomnia, those with sleep-onset insomnia have more motor, cognitive, and autonomic signs/symptoms. When evaluating neurodegenerative risk, differentiating insomnia subtypes may increase precision. Yao CW, Pelletier A, Fereshtehnejad S-M, Cross N, Dang-Vu T, Postuma RB. Insomnia symptom subtypes and manifestations of prodromal neurodegeneration: a population-based study in the Canadian Longitudinal Study on Aging. J Clin Sleep Med. 2022;18(2):345-359.

Characterization of sleep in six patients with pantothenate kinase-associated neurodegeneration

BackgroundPantothenate kinase-associated neurodegeneration (PKAN) is a rare neurologic disorder included in the group of neurodegeneration with brain iron accumulation diseases (NBIA). Information regarding sleep in patients with PKAN is limited. ObjectivesTo describe the clinical and polysomnographic characteristics of sleep in six patients with genetically confirmed PKAN. MethodsThe evaluation included a clinical interview, sleep questionnaires -Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS)- and a video-polysomnography (VPSG). In addition to standard sleep measures we manually quantified sleep spindle density in stage N2 and rapid eye movements in REM sleep comparing the results with matched controls. Quantification of EMG activity in REM sleep was performed following standard criteria. ResultsAll the patients reported at least one sleep complaint, most commonly sleep fragmentation (4/6) and sleep onset insomnia (3/6). ESS and PSQI were abnormal in 3/6 and 4/6, respectively. VPSG showed in 4/6 decreased ocular movements during REM sleep, an increase in sleep spindles in 3/6 (all of them with deep brain pallidal stimulation), an absence of slow wave sleep in 2 and undifferentiated NREM sleep and delayed sleep phase in one. Three patients had an abnormal sleep apnea/hypopnea index, and 2 periodic limb movements of sleep. REM sleep muscular atonia was preserved in all. ConclusionsSleep disorders are common in patients with PKAN. Although our sample is small and heterogeneous, with different symptomatic treatments possibly influencing the results, it suggests that evaluation of sleep should be considered in their management.

Sleep microstructure in attention deficit hyperactivity disorder according to the underlying sleep phenotypes.

The analysis of sleep microstructure in attention deficit hyperactivity disorder (ADHD) revealed an under-representation of the EEG slow component during NREM sleep. Previous studies either excluded or did not characterize objectively sleep disorders, which notoriously affect sleep architecture. The present study aimed to investigate the cyclic alternating pattern in a real clinical sample of children with ADHD, in whom sleep disorders could be considered. Twenty-seven consecutively enrolled drug-naïve children (mean age, 10.53 years; nine females) and 23 controls (mean age, 10.22years; 11 females) underwent a full sleep investigation, including attended video-polysomnography. Visual cyclic alternating pattern analysis was performed in a blinded way. Children with ADHD had one or more sleep disorders (a narcolepsy-like phenotype was found in two cases, sleep onset insomnia in three cases, arousal disorder in one case, movement disorder phenotype in six cases and obstructive sleep apnea in 11 cases, and six children had sleep-related epileptiform discharges). Children with ADHD and normal controls showed a similar microstructure with a cyclic alternating pattern rate of about 50%. Children with obstructive sleep apnea had a significantly higher cyclic alternating pattern rate during stage N3. Despite not reaching statistical differences, a lower cyclic alternating pattern rate and A1 index were found in children without epileptic abnormalities/obstructive sleep apnea. Our analysis might allow differentiation of the "primary form" of ADHD associated with a decrease of NREM instability from those forms associated with sleep apnea and epileptic activity.

The relationship between insomnia symptoms and frailty in community-dwelling older persons: a path analysis

BackgroundThe relationship between sleep and frailty in older age is complex. Most previous studies focused on sleep duration, while insomnia, a common sleep problem in older adults, has not been adequately examined and the factors implicated in its association with frailty were under-explored. MethodsA community-based sample of 345 prefrail and frail older adults were recruited and completed the measures on insomnia symptoms (Pittsburgh Sleep Quality Index) and frailty status (FRAIL Scale). The relationship between insomnia symptoms and frailty, with potential mediators including physical performance (Short Physical Performance Battery), depression (Patient Health Questionnaire-9), and level of physical activity (Physical Activity Scale for the Elderly), were tested in path analysis adjusting for age, gender, body mass index and sleep medications. ResultsThe prevalence of sleep-onset insomnia was higher in frail participants than their prefrail counterparts (48% vs. 34%, aOR = 1.73; 95% CI 1.09, 2.76; p = 0.02), but there was no significant difference in the prevalence of sleep-maintenance insomnia (61% vs. 54%). The association between sleep-onset insomnia and frailty was explained by reduced physical performance (standardized coefficient = 0.11; 95% BCa CI [0.002, 0.233]), but not depression and level of physical activity. Sleep-maintenance insomnia was not associated with frailty. ConclusionsInsomnia symptoms are prevalent in frail and prefrail older adults. Sleep-onset insomnia is associated with poorer physical performance, which is further linked to a higher risk for frailty in older persons. The findings highlight the importance of timely assessing and managing insomnia among older adults at risk of frailty.

National Survey on the importance of sleep in the quality of academic life and mental health of college students in Portugal.

The academic years are a period of vulnerability when considering sleep problems and mental health. Growing evidence suggests poor sleep patterns are related to impaired academic life and lower psychological well-being. The aim of this study was to explore the importance of sleep habits and report the associations of sleep problems with quality of academic life and different dimensions of mental health (e.g. worries, anxiety, self-regulation and resilience) in a large sample of college students. The HBSC/JUnP data base comprises a representative sample of 2991 college students (n=2203; 73.7% women), aged from 18 to 35 years old (22.43±3.83). Participants socio-demographic characteristics included sex and age. Besides, participants were inquired about sleep duration, characteristics of their sleep habits, questions about quality academic life, namely feeling bored in university, pressure from academic work and academic performance perception and mental health, namely worries, anxiety, self-regulation and resilience. Results showed most young people report an average value for sleep habits (M=4.41; SD=1.46) and that they sleep an average of 7 hours a night. More than half of the young people report either being affected by difficulty falling asleep, showing signs of sleep onset insomnia (67.7%). The conducted analyses indicated that the difficulty falling asleep (having insomnia) was associated with poor/reasonable academic performance perception, higher levels of concerns and anxiety, and lower levels of self-regulation and resilience, thus jeopardizing the mental health of college students. In turn, that characteristics of sleep was also associated with poor sleep habits. In conclusion, this study showed that poor sleep habits were associated with a worse level of academic performance perception and low levels of mental health among college students in Portugal. Universities offer enormous potential as settings to promote sleep-health programs since they can reach many young people who are future-oriented and willing to learn. There is then the need for academic researchers, teaching staff and health professionals working for college students health, to develop and test a wide array of sleep-promoting interventions (e.g., education classes, online programs, adjustment of class time), thus preventing negative secondary outcomes.

332 Non-REM EEG Spectral Power at Baseline and After Total Sleep Deprivation in Individuals with Sleep-Onset Insomnia

Abstract Introduction The baseline non-REM sleep EEG of individuals with insomnia has been found to display increased spectral power at frequencies &amp;gt;14Hz, which may reflect hyperarousal. There is some evidence in this population of reduced slow wave activity after total sleep deprivation (TSD), potentially indicating altered sleep homeostasis. We investigated non-REM sleep EEG spectra at baseline and after TSD in individuals with sleep-onset insomnia. Methods 10 individuals with sleep-onset insomnia and 5 healthy controls (ages 22-40y, 11 females) completed a 5-day laboratory study with an adaptation night, baseline night, assignment to 38h TSD (n=5 insomnia, n=5 control) or equivalent non-TSD control (n=5 insomnia), and recovery night. Sleep periods were 10h (22:00-08:00) with digital polysomnography (250Hz; Nihon Kohden). Following artifact rejection, 5s subepochs of the non-REM (stages N2, N3) sleep EEG (C3-M2 derivation) in baseline and recovery nights were subjected to spectral analysis. Spectra (0.2Hz bins) were averaged over subepochs in 30s epochs. Repeated-measures ANOVA compared baseline spectra between insomnia and controls, and baseline-recovery difference spectra between TSD insomnia, non-TSD insomnia, and TSD controls. Results Average non-REM sleep amount was 5.9 at baseline, increasing by 1.1h after TSD, with no differences between groups (p≥0.20). At baseline, the insomnia group showed increased power in theta/alpha (~4–12Hz), reaching significance in the lower spindle range, compared to controls (p&amp;lt;0.05). As anticipated, no differences emerged between baseline and recovery nights in the non-TSD insomnia group. However, the TSD insomnia group showed increased delta (~1–3Hz) and theta/alpha (~6–10Hz) power (p&amp;lt;0.05) during recovery. Healthy controls showed expected power increases in delta and lower spindle range, and decreases in upper spindle range (~14–15Hz), after TSD (p&amp;lt;0.05). Conclusion Compared to healthy controls, individuals with sleep-onset insomnia showed increased non-REM sleep EEG power in the theta/alpha bands and low spindle frequency range, with further significant increases in theta/alpha in addition to delta power following TSD, despite small sample size. The increase in delta power following TSD was equivalent to that in healthy controls, suggesting no sleep homeostasis abnormality. Whether the elevated theta/alpha power may be related to hyperarousal is unclear. Support (if any) ONR grant N00014-13-C-0063

401 Clinical Phenotypes of Obstructive Sleep Apnea in World Trade Center Responders

Abstract Introduction The heterogeneity of symptoms in obstructive sleep apnea (OSA) patients has been recently formalized into 3 distinct clusters: Sleepy, Disturbed Sleep, and Minimally Symptomatic. Our previous data showed that OSA is highly prevalent (&amp;gt;75%) in World Trade Center (WTC) responders, and positive airway pressure (PAP) treatment adherence is very poor (&amp;lt;20%). To better understand the heterogeneity of OSA in the WTC cohort, here we sought to examine the distribution of these distinct clinical phenotypes. Methods 643 subjects with no history of OSA or reported loud and frequent snoring before 9/11/2001 from the WTC health program clinical centers at Rutgers RWJMS, New Jersey, NYU School of Medicine, and Icahn School Medicine at Mount Sinai, New York underwent 2 nights of home sleep testing using the ARES unicorder (SleepMed, Inc., West Palm Beach, FL, USA). Epworth Sleepiness Scale (ESS), sleep onset insomnia, and sleep maintenance insomnia were assessed with questionnaires. OSA was defined as (AHI4%&amp;gt;=5 or RDI&amp;gt;=15/hr). The three clusters were defined as 1) Sleepy (ESS&amp;gt;10 and/or sleep onset/maintenance insomnia); 2) Disturbed Sleep (not sleepy (ESS&amp;lt;=10) and sleep onset/maintenance insomnia); and 3) Minimally Symptomatic (not sleepy (ESS&amp;lt;=10) and no sleep onset/maintenance insomnia). Distribution of clusters in the WTC cohort was compared to published data from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Results Among the subjects diagnosed with OSA (N 440; AHI4%=13(15); RDI =28(19); median(iqr); 81% men; age, 33–87 years; BMI, 27.4±3.7 kg/m2), the distribution of clinical phenotypes was 31.4% sleepy, 48.9% disturbed sleep, and 19.7% minimally symptomatic, and did not differ between OSA severity groups. In comparison to SAGIC and HCHS/SOL, the WTC cohort exhibited significantly increased prevalence of the disturbed sleep phenotype (WTC vs SAGIC: 48.9% vs. 19.8%, □2=54.9; p&amp;lt;0.001; WTC vs. HCHS/SOL: 48.9% vs. 38.1%, □2=26.1, p&amp;lt;0.001). Conclusion The predominant clinical phenotype of OSA in the WTC cohort is disturbed sleep (insomnia) and its prevalence is significantly greater than what has been observed in other large OSA cohorts. These findings may help explain the poor adherence to PAP treatment observed in the WTC cohort. Support (if any) NIOSH U01OH01415; AASM Foundation 233-BS-20.

537 Insomnia Symptoms and Subsequent Cognitive Performance in Older Adults: Are Depressive Symptoms and Vascular Disease Mediators?

Abstract Introduction Alzheimer’s disease and related dementias (ADRD) are growing public health concerns, and poor sleep may represent a modifiable risk factor. However, there is limited research on insomnia as a predictor of subsequent performance in different cognitive domains and mechanisms that might underlie domain-specific associations. The current study examined: (1) which insomnia symptoms predicted performance across five cognitive domains 14 years later, and (2) whether depressive symptoms and/or vascular diseases mediated these associations. Methods Participants included 2,496 adults aged 51+ in the Health and Retirement Study. Insomnia symptoms in 2002 (i.e., “baseline”) were quantified by four self-reported items on frequency of trouble falling asleep, nighttime awakenings, early awakenings, and feeling rested upon awakening. Cognition was assessed in 2016 as part of the Harmonized Cognitive Assessment Protocol and operationalized with five factor scores corresponding to episodic memory, executive function, language, visuoconstruction, and processing speed. Multiple regressions examined associations between baseline insomnia symptoms and subsequent cognitive performance, controlling for sociodemographics and baseline global cognitive performance. Mediation models tested whether associations were explained by self-reported depressive symptoms and/or vascular diseases (i.e., hypertension, heart disease, diabetes, and/or stroke) in 2014, controlling for baseline values. Results Only trouble falling asleep in 2002 was associated with cognition in 2016. Specifically, more frequent trouble falling asleep predicted poorer episodic memory, executive function, language and processing speed performance, but not visuoconstruction. These associations were mediated by depressive symptoms and vascular diseases in 2014 for all domains except episodic memory; only depressive symptoms mediated the association involving memory. After accounting for these mediators, direct effects of trouble falling asleep remained for episodic memory, executive function and language, but not processing speed. Conclusion Difficulty with sleep initiation may be more consequential for later-life cognition than other insomnia symptoms. Depressive symptoms and vascular diseases may partially drive these associations. We speculate that sleep-onset insomnia could mean less total sleep, immune dysfunction, or endocrine effects that worsen mood, vascular health, and cognition. Remaining associations indicate that additional research is needed to characterize other mechanisms through which sleep initiation problems could contribute to later impairments in frontal and temporal cognitive systems, which are implicated early in ADRD. Support (if any):