Understanding Anxiety in Cervical Dystonia: An Imaging Study.

BACKGROUND: Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate. OBJECTIVE: To investigate brain networks associated with anxiety in CD. METHODS: Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales. RESULTS: Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05). CONCLUSION: Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.

Practical applications of teledentistry during the Covid-19 pandemic in ASEAN member states - a systematic review.

OBJECTIVE: The objective of this review is to determine the utilisation and adoption of teledentistry based solutions and technologies during the Covid-19 Pandemic in the Asean region. BACKGROUND: Teledentistry is a branch of telemedicine that has rapidly advanced in the last few years and has the potential to provide solutions to oral health problems of patients and locations that do not have prompt and immediate access to a dentist or dental services. The Covid-19 has increased the adaption of all digital health technologies and teledentistry is no exception. METHODOLOGY: The study utilized online databases such as Pubmed (Medline), Scopus (Embase) and CINAHL for the purpose of document search. Newcastle Ottawa (NOS) scale was used to determine the quality of the studies included in our systematic review. PRISMA guidelines were used as the criteria for reporting items in the systematic review. RESULTS: A total of 1297 documents were found after applying the search criteria and the keywords for the selected study. After applying the Prisma guidelines, removal of duplicates and irrelevant entries, 10 studies that were conducted during the Covid-19 pandemic were selected, fitting the inclusion criteria. All the studies included were evaluated for quality and risk of bias through the Newcastle Ottawa scale. Only high-quality studies were included for the final review. CONCLUSION: Teledentistry is a cost-effective solution to screen, diagnose and treat dental patients from a distance. Teledentistry also has the potential to continue seamless continuation of dental education to dental students, during disruptive and non-disruptive periods. ASEAN countries should fully utilise the potential of teledentistry, however sound and effective legislation would be the key first step to achieving that potential.

Altered Impulsivity Across Drug-Naïve Parkinsonism, Isolated Rapid Eye Movement Sleep Behavior Disorder, and Their High-Risk Relatives.

OBJECTIVE: To determine multidimensional impulsivity levels across different early stages of α-synucleinopathy. METHODS: This cross-sectional study investigated motor and decisional impulsivity levels using a panel of computerized tasks among drug-naïve parkinsonism patients, isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) patients and their first-degree relatives (iRBD-FDRs), and control participants. Trait impulsivity and impulse control behaviors were assessed by self-reported questionnaires. RESULTS: A total of 27 drug-naïve parkinsonism patients, 157 iRBD patients, 66 iRBD-FDRs, and 82 control participants were recruited. Parkinsonism and iRBD patients had fewer numbers of extracted beads in beads task 1 and 2 (both p < 0.001), and a higher rate of irrational choice in task 1 (p = 0.046) before making decisions, and fewer numbers of pumps of unexploded blue balloons in the balloon analog risk task (p = 0.004) than control participants, indicating a higher level of reflection impulsivity and a lower level of risk taking, respectively. iRBD patients had more no-go errors in the go/no-go task than control participants (padjusted = 0.036), suggesting a higher level of motor impulsivity. iRBD-FDRs with dream-enactment behaviors had fewer numbers of extracted beads (p = 0.047) in beads task 2 than FDRs without dream-enactment behaviors, suggesting a possible higher level of reflection impulsivity. INTERPRETATION: A complex construct of altered impulsivity with decreased risk taking, but increased reflection and motor impulsivity, has already occurred at the prodromal and early stages of α-synucleinopathy, which have implications for underlying pathophysiology and clinical management of α-synucleinopathy, especially for impulse control behaviors upon dopaminergic drug treatment. ANN NEUROL 2024;95:544-557.

School-Based Sleep Education Program for Children: A Cluster Randomized Controlled Trial.

Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: -0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children's sleep-wake patterns and sleep problems.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

Early- and late-onset of isolated rapid eye movement sleep behavior disorder: A retrospective cohort study.

OBJECTIVE: Age at onset of neurodegenerative disease has significant implications in differentiating disease profiles. We aimed to determine whether age at onset could identify clinical and neurodegenerative profiles in patients with isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) - a prodromal stage of α-synucleinopathies. METHODS: In this retrospective cohort study, the time of the first episode of dream-enactment behaviors that the patient/bed-partners recalled at the time of the patient's first visit to sleep clinic was collected. The distribution of age at onset was examined and patients were dichotomized into early- and late-onset groups based on the intersection point of underlying two Gaussian distributions of onset age. RESULTS: A total of 241 patients were included. The intersection of underlying two Gaussian models of onset age was 64.6 years, yielding 168 early- (median onset age: 58.0 years, range: 38.0-64.0) and 73 late-onset patients (median onset age: 70.0 years, range: 65.0-82.0). Among them, 154 of early- and 68 late-onset patients were followed-up. Late-onset patients had milder RBD symptoms, but worse sleep, cognition, olfactory and motor functions, and a higher risk of phenoconversion (adjusted hazard ratio (aHR) = 2.2, 95% confidence interval (CI) = 1.2-3.9), especially to probable dementia with Lewy bodies (DLB) (aHR = 8.9, 95% CI = 3.0-26.2), than early-onset patients. CONCLUSIONS: Late-onset iRBD was associated with a higher level of neurodegenerative markers and a quicker phenoconversion, especially to probable DLB. Age at onset of iRBD could help identify clinical features and predict prognosis of iRBD.

Isolated dream-enactment behaviours as a prodromal hallmark of rapid eye movement sleep behaviour disorder.

Recurrent dream-enactment behaviours (DEB) and rapid eye movement (REM) sleep without atonia (RSWA) are two diagnostic hallmarks of REM sleep behaviour disorder (RBD), a specific prodrome of α-synucleinopathy. Whilst isolated RSWA (without DEB) was suggested as a prodrome of RBD, the implication of 'isolated' recurrent DEB remains under-investigated. In this cross-sectional study, we sought to investigate neurodegenerative markers amongst the first-degree relatives (FDRs, aged >40 years) of patients with RBD who underwent clinical assessment for DEB, neurodegenerative markers, and video-polysomnography assessment. Isolated recurrent DEB was defined as: (i) three or more episodes of DEB, (ii) had a DEB episode in the past 1 year, and (iii) subthreshold RSWA. We identified 29 FDRs (mean [SD] age 53.4 [8.3] years, 55.2% male) with isolated recurrent DEB and 98 age and sex-matched FDRs as controls. Isolated DEB was associated with nightmare (27.6% versus 11.2%, p = 0.02), and the DEB group had a higher rate of current smoking (27.6% versus 3.1%, p = 0.006), type 2 diabetes mellitus (24.1% versus 10.2%, p = 0.003), anxiety disorder (24.1% versus 11.2%, p = 0.02), and constipation (hard lump of stool, 31.0% versus 7.1%, p < 0.001) than the control group. The present findings revealed that family relatives of patients with RBD with isolated recurrent DEB have increased risk of RBD and neurodegenerative features, which adds to the emerging data that isolated DEB is a prodromal feature of RBD and α-synucleinopathy neurodegeneration.

The impact of sleep-corrected social jetlag on mental health, behavioral problems, and daytime sleepiness in adolescents.

STUDY OBJECTIVES: This study aimed to examine the effect of sleep-corrected social jetlag (SJLsc) on mental health, behavioral problems, and daytime sleepiness in adolescents. METHODS: This was a cross-sectional study which included 4787 adolescents (Mean age: 14.83±1.6y, 56.0% girls) recruited from 15 secondary schools in Hong Kong. SJLsc was defined as the absolute difference between sleep-corrected midsleep on weekdays and weekends, at which the sleep debt has been considered. It was classified into three groups: low-level ("LSJLsc", <1h), mid-level ("MSJLsc", ≥1h and <2h), and high-level of SJLsc ("HSJLsc", ≥2h). Adolescents' mental health, behavioral problems and daytime sleepiness were measured by the General Health Questionnaire (GHQ-12), the Strengths and Difficulties Questionnaire (SDQ) and the Pediatric Daytime Sleepiness Scale (PDSS). Logistic regression analysis and restricted cubic spline regression (RCS) analysis were applied with consideration of confounders including age, gender, puberty and sleep problems. RESULTS: Nearly half (46.9%) of adolescents had SJLsc for at least 1 h. Greater SJLsc was associated with more behavioral difficulties (MSJLsc: OR: 1.20, p = 0.03; HSJLsc: OR: 1.34, p = 0.02) when controlling for age, sex, puberty, chronotype, insomnia, and time in bed. There was a dose-response relationship in which higher SJLsc had an increased risk of conduct problems and hyperactivity, while only high-level SJLsc was associated with a peer relationship problem. In RCS analysis, SJLsc was associated with a higher likelihood of behavioral difficulties (p = 0.03) but not poor mental health or daytime sleepiness. CONCLUSIONS: Sleep-corrected social jetlag was a unique risk factor for behavioral problems in adolescents. Our findings highlighted the need for interventions to promote healthy sleep-wake patterns in school adolescents.

Evolution of Prodromal REM Sleep Behavior Disorder to Neurodegeneration: A Retrospective Longitudinal Case-Control Study.

BACKGROUND AND OBJECTIVES: Individuals with a history of recurrent dream-enactment behaviors, but with subthreshold REM sleep without atonia levels for REM sleep behavior disorder (RBD) diagnosis, are currently classified to have prodromal RBD (pRBD). However, the REM sleep-elevated EMG diagnostic cutoff, progression trajectory, and long-term neurodegenerative outcome of pRBD are not well understood. This study aimed to delineate the evolution of REM sleep EMG levels, determine the EMG cutoff score for diagnosing pRBD, and examine the risk for neurodegenerative diseases of pRBD. METHODS: This retrospective longitudinal case-control study recruited patients with pRBD and age-matched, sex-matched, and follow-up duration-matched controls who were free of neurodegenerative disease at baseline in the Sleep Assessment Unit, the Chinese University of Hong Kong from 1997 to 2018. Patients and controls underwent clinical and video-polysomnography (PSG) assessments at baseline and follow-up(s). REM sleep EMG activity level on mentalis and anterior tibialis (AT) muscles on video-PSG at each visit was scored. The diagnosis of neurodegenerative diseases was confirmed by a neurologist. RESULTS: A total of 44 patients (age 67.4 ± 8.2 years, 6 females) and 44 controls were recruited. The combined REM sleep EMG level on mentalis and AT muscles of patients with pRBD significantly increased during 8.2 ± 3.3 years of follow-up (from 19.3% ± 9.7% to 47.3% ± 27.4% with estimated annual increase of 3.9%), yielding 29 patients with pRBD (66%) meeting the full-blown RBD diagnostic criteria. Baseline REM sleep mentalis and AT muscles EMG activity of patients who developed full-blown RBD could favorably differentiate pRBD from controls (6.3% for mentalis "any" and 9.1% for combination of mentalis any and bilateral AT muscles phasic EMG with an area under the curve of 0.88 [0.78-0.98] and 0.97 [0.92-1.00], respectively). Patients with pRBD had a higher risk for neurodegenerative diseases (9 developed Parkinson disease and 3 developed dementia with Lewy bodies) when compared with controls (5 developed Alzheimer disease, adjusted hazard ratio = 2.95, 95% CI = 1.02-8.54). DISCUSSION: pRBD has a predictive progression in both pathophysiology and neurodegenerative outcome. This finding has significant implications to the nosological status of pRBD, the current REM sleep-related EMG diagnostic criteria, spectrum concept of RBD, and future neuroprotective intervention. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EMG activity during REM sleep predicts the development of pRBD.

Efficacy of Email-delivered Versus Face-to-face Group Cognitive Behavioral Therapy for Insomnia in Youths: A Randomized Controlled Trial.

PURPOSE: The purpose of the study was to compare the efficacy of group-based therapy (GT) and email-delivered self-help (ESH) cognitive behavioral therapy for insomnia (CBT-I) with the wait-list (WL) control group in youths. METHODS: The study involved an assessor-blind, parallel group randomized controlled trial in youths meeting the diagnostic criteria for insomnia disorder. Participants were randomized to one of the three groups (8-week GT, 8-week ESH, or WL). Participants in all three groups were assessed at baseline and after treatment (week 9 for the WL group). The two treatment groups were additionally assessed at one month and six months after the intervention. Treatment effects were examined using linear mixed models. RESULTS: A total of 135 youths (mean age: 20.0 ± 2.5 years, female: 67.4%) were recruited. After treatment, both active treatment groups showed significant improvements in insomnia symptoms (GT vs. WL: Cohen's d = -1.03, ESH vs. WL: d = -.63), less presleep arousal (d = -.52 to -1.47), less sleep-related dysfunctional belief (d = -.88 to -1.78), better sleep hygiene practice (d = -.79 to -.84), and improved daytime functioning (d = -.56 to -.96) compared with the WL group. In addition, GT outperformed ESH in improving maladaptive sleep-related beliefs and mood symptoms at post-treatment and 6-month follow-up. A reduction of suicidality with moderate effect size favoring GT emerged at 6-month follow-up. DISCUSSION: Our findings suggested that both group-based and email-delivered CBT-I were effective in treating youth insomnia, but group-based CBT-I showed superior effects on reducing maladaptive beliefs and mood symptoms.

Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: a two-phase study.

OBJECTIVE: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD). METHODS: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria. RESULTS: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD. CONCLUSIONS: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.

A Prevention Program for Insomnia in At-risk Adolescents: A Randomized Controlled Study.

OBJECTIVES: To prevent the future development of insomnia in at-risk adolescents. METHODS: A randomized controlled trial comparing 4 weekly insomnia prevention program with a nonactive control group. Subjects were assessed at baseline, postintervention, and 6 and 12 months after intervention. Assessors were blinded to the randomization. Analyses were conducted on the basis of the intention-to-treat principles. RESULTS: A total of 242 adolescents with family history of insomnia and subthreshold insomnia symptoms were randomly assigned to an intervention group (n = 121; mean age = 14.7 ± 1.8; female: 51.2%) or control group (n = 121; mean age = 15.0 ± 1.7; female: 62.0%). There was a lower incidence rate of insomnia disorder (both acute and chronic) in the intervention group compared with the control group (5.8% vs 20.7%; P = .002; number needed to treat = 6.7; hazard ratio = 0.29; 95% confidence interval: 0.12-0.66; P = .003) over the 12-month follow-up. The intervention group had decreased insomnia symptoms (P = .03) and reduced vulnerability to stress-related insomnia (P = .03) at postintervention and throughout the 12-month follow-up. Decreased daytime sleepiness (P = .04), better sleep hygiene practices (P = .02), and increased total sleep time (P = .05) were observed at postintervention. The intervention group also reported fewer depressive symptoms at 12-month follow-up (P = .02) compared with the control group. CONCLUSIONS: A brief cognitive behavioral program is effective in preventing the onset of insomnia and improving the vulnerability factors and functioning outcomes.

Residual Injurious Symptoms and Its Association With Neurodegenerative Outcomes in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Retrospective, Longitudinal Follow-up Study.

BACKGROUND: The risk of neurodegenerative disorders in idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with residual injurious symptoms (RIS) after symptomatic treatment with clonazepam and/or melatonin is unclear. OBJECTIVE: The objective of this study was to determine the rate and correlates of RIS and its association with the risk of neurodegenerative diseases in patients with iRBD. METHODS: This was a retrospective cohort study. RIS was defined by the RBD Questionnaire-Hong Kong (RBDQ-HK) as the presence of residual sleep-related injuries or potential injurious behaviors for at least once a month after at least 1 year of treatment. RESULTS: A total of 15 out of 133 (11.3%) patients with iRBD (age at diagnosis = 66.5 ± 7.3 years, 77.4% male) had RIS after 2.7 years of treatment. Patients with RIS were younger at both onset and polysomnography-confirmed diagnosis of iRBD (years, mean ± standard deviation, 56.3 ± 6.9 vs. 61.8 ± 7.6, P = 0.01; 61.2 ± 4.2 vs. 67.2 ± 7.4, P < 0.001, respectively), had more severe behavioral symptoms at diagnosis (both RBDQ-HK total score and behavioral subscore, P = 0.01), and used a higher maximum dose of clonazepam (mg; median [interquartile range], 1.5 [1.0] vs. 1.0 [1.0], P = 0.01). RIS was probably associated with a higher risk of developing dementia with Lewy bodies (adjusted hazard ratio [95% confidence interval], 5.47 [1.71-17.46], adjusted for onset age of RBD), but not Parkinsons's disease in the follow-up. CONCLUSION: RIS is not uncommon in patients with iRBD despite long-term medication treatment. An earlier onset and more severe clinical profile are associated with RIS. The prediction of RIS toward dementia with Lewy bodies but not PD suggests that RIS may probably help to identify the specific risk of different subtypes of α-synucleinopathy. © 2020 International Parkinson and Movement Disorder Society.

Rest-Activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE: The purpose of this study was to investigate the differences in actigraphy-measured rest-activity patterns (eg, sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy. METHODS: We compared alterations in 7-day actigraphy-measured rest-activity patterns among patients with clinically diagnosed α-synucleinopathies (n = 44), and their age-, sex-, and body mass index (BMI)-matched patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, n = 88), and non-rapid eye movement (REM) sleep behavior disorder (RBD) controls (n = 44) in a case-control study (study 1) and between convertors (n = 22) and their age-, sex-, BMI-, iRBD-duration, and follow-up duration-matched non-convertors (n = 66) in a prospective nested case-control study (study 2). RESULTS: In study 1, there were significant increases (all p values were adjusted by false discovery rate < 0.01) in probable napping behaviors (percentage, duration, and episodes), activity fragmentation (estimated by kAR ), and physical inactivity during active periods across controls, and iRBD, to clinically diagnosed α-synucleinopathies. In study 2, higher levels (all p values were adjusted by false discovery rate < 0.05) of baseline objective probable napping, activity fragmentation, and physical inactivity during active periods were associated with the conversion of patients with iRBD into clinically diagnosed α-synucleinopathies at 2 years of follow-up with medium to large effect sizes (Cohen's d: 0.56 to 0.80). These findings were further supported by functional linear modeling analyses. INTERPRETATION: Rest-activity pattern alterations, mainly objective probable napping behaviors, activity fragmentation, and physical inactivity during active period, emerge as early as at the stage of iRBD, which serves as early and robust prodromal markers of the conversion of iRBD into clinically diagnosed α-synucleinopathies. ANN NEUROL 2020;88:817-829.

Electromyography activity level in rapid eye movement sleep predicts neurodegenerative diseases in idiopathic rapid eye movement sleep behavior disorder: a 5-year longitudinal study.

OBJECTIVES: To investigate whether baseline electromyography (EMG) activity during rapid eye movement (REM) sleep predicts the development of neurodegenerative diseases over time in patients with idiopathic REM sleep behavior disorder (iRBD). METHODS: A total of 216 patients with polysomnography-confirmed iRBD were recruited from September 1997 to December 2016 with a mean follow-up duration of 5.0 ± 3.7 years (median: 4.0, range: 0.5-19.0). Neurodegenerative diseases were ascertained according to standard diagnostic criteria during follow-up. Time-dependent receiver operating characteristic (ROC) curves were employed to evaluate the dynamic predictive performance of EMG activity over time. Both tonic and phasic EMG activity were dichotomized into 'mild' and 'severe' categories by the ROC curves estimated optimal cut-offs. RESULTS: A total of 58 patients (26.9%) developed neurodegenerative diseases. The predictive performance of tonic EMG activity was stable (area under the curve of approximately 0.68) over time, while the performance of phasic EMG activity was significantly superior to chance only after five years of follow-up. The optimal cut-off for prediction at five years was 15.4% (sensitivity, 0.69; specificity, 0.57) and 7.8% (sensitivity, 0.79; specificity, 0.47) for tonic and phasic EMG activity, respectively. Cox proportional hazards regression analyses further revealed that severe tonic (adjusted HR: 2.76, 95% CI: 1.35-5.62) and phasic EMG activity (adjusted HR: 3.10, 95% CI: 1.10-8.71) were associated with early development of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), respectively. CONCLUSIONS: Tonic but not phasic EMG activity may serve as a stable biomarkers for predicting the progression of neurodegeneration in iRBD.

A case-control-family study of idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers. METHODS: A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively. RESULTS: Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03). INTERPRETATION: iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.

Excessive daytime sleepiness among children and adolescents: prevalence, correlates, and pubertal effects.

OBJECTIVES: To examine the prevalence and correlates of excessive daytime sleepiness (EDS) among Hong Kong children and adolescents. We investigated the potential roles of sex and puberty in modulating the occurrence of EDS. METHODS: A total of 10,086 students (male, 48.1%) aged 6-18 (mean ± SD: 12.3 ± 3.2) years old participated in this cross-sectional survey. EDS was defined by a total score >18 on the Pediatric Daytime Sleepiness Scale. Sociodemographic characteristics, time in bed, chronotypes, sleep problems, emotional and behavioral difficulties, mental health, and pubertal stages were assessed. RESULTS: The overall prevalence of EDS was 29.2%, and increased from 19.8% at Tanner stage 1 (pre-puberty) to 47.2% at Tanner stage 5 (post-puberty). Female predominance emerged at Tanner stage 3 (mid-puberty). EDS was significantly associated with short weekday time in bed, both long and short weekend time in bed, eveningness chronotype, insomnia symptoms, and sleep-disordered breathing symptoms. Females were more likely to have short weekday time in bed and eveningness chronotype than males. Children and young adolescents at pre and mid-puberty were protected against EDS by morningness chronotype. EDS was independently associated with daytime napping, alcohol and energy beverage consumption, emotional and behavioral difficulties, as well as poor mental health even after adjusting for potential confounding factors. CONCLUSIONS: EDS is prevalent among children and adolescents with the emergence of female preponderance at mid-puberty and independent association with pervasive adverse emotional and behavioral problems. The mechanisms underlying the modulation effects of sex and puberty on EDS merit further investigation.

Associations of Homer Scaffolding Protein 1 gene and psychological correlates with suicide attempts in Chinese: A pilot study of multifactorial risk model.

BACKGROUND: Suicide is a fatal outcome for subjects with mental ill-health. Genetic factors and psychological correlates are believed to contribute to the risk of suicide attempts (SA), whereas both factors are reported to exert a small effect. This study therefore tried to investigate if combination of the two aspects can enhance the explanation of variance in SA. METHODS: A common variant rs7713917 in HOMER1 gene was genotyped for 333 Chinese psychiatric patients with or without SA. Multifactorial risk models comprised of this variant and psychological correlates were identified by logistic regression analysis (LRA) and Multifactor Dimensionality Reduction (MDR) method separately, and then evaluated for their performance by biostatistical methods. RESULTS: An association of A-carrier genotypes in rs7713917 with an increased risk of SA was observed (OR = 1.79, 95% CI = 1.08-2.98). Although with a medium effect size, this variant alone could only explain 1.9% variance of SA. Interestingly, this study was the first time to show that the association of the rs7713917 and SA was significantly mediated by the NEO conscientiousness (NEOC) dimension (p-value = 0.002), with a greater genetic effect observed in subjects with a low NEO-C level (OR = 2.89, 95% CI = 1.16-7.18) but not in subjects with an average or high level. Upon the LRA method, the multifactorial risk model constituted of the two interacted factors and their interaction effect could explain up to 17.0% variance, which was almost 9-fold higher than the one explained by the rs7713917 alone. Furthermore, this model owned a higher effectiveness than the three models identified by the MDR method (p-value < 0.0007). CONCLUSIONS: The present study identified an effective multifactorial risk model, in which the combination of the HOMER1 variant and the NEO-C dimension could enhance explanation of the variance of SA in Chinese. This pilot study may provide a novel avenue to investigate the pathogenesis of SA in psychiatric patients.

Eveningness chronotype, insomnia symptoms, and emotional and behavioural problems in adolescents.

OBJECTIVE: Eveningness tendency and insomnia are common in adolescents, but whether they have an independent or synergistic effect on the risk of psychopathology have remained undefined. The present study aimed to examine eveningness chronotype and insomnia symptoms in relation to mental health and emotional and behavioural problems in a community-based adolescent population. METHODS: A total of 4948 adolescents (weighted mean age: 14.5 ± 1.8 years, weighted percentage of females: 48.9%) completed the measures. Insomnia was assessed by the Insomnia Severity Index (ISI), and chronotype preference was measured by the reduced version of the Morningness-Eveningness Questionnaire (MEQ). Emotional and behavioural problems and mental health were assessed by the Strengths and Difficulties Questionnaire (SDQ) and the General Health Questionnaire (GHQ-12), respectively. Potential confounders including demographic factors, pubertal status, general health, and sleep duration were controlled for in the analyses. RESULTS: Insomnia symptoms were prevalent in evening-type adolescents (52% vs intermediate-type: 34.3%, morning-type: 18.0%, p < 0.001), especially two subtypes of insomnia symptoms, including difficulty initiating sleep and difficulty maintaining sleep. Eveningness and insomnia were independently associated with an increased risk of having emotional and behavioural problems (eveningness: adjusted odds ratio [AdjOR] = 1.88, 95% confidence interval [CI] = 1.61-2.19, p < 0.001; insomnia: AdjOR = 3.66, 95% CI = 2.73-4.91) as well as poor mental health in adolescents (eveningness: AdjOR = 1.25, 95% CI = 1.04-1.52, p < 0.001; insomnia: AdjOR = 3.63, 95% CI = 2.41-5.03). CONCLUSIONS: Eveningness and insomnia symptoms are independently associated with the risk of psychopathology in adolescents. Our findings underscore the need to address both sleep and circadian factors in assessing and managing emotional and behavioural problems in the adolescent population.

Impact of a modest delay in school start time in Hong Kong school adolescents.

OBJECTIVE: To examine the effects of a modest delay (15 min) in school start time (SST) on adolescent sleep patterns, mood, and behaviors. METHODS: Two secondary schools in Hong Kong with a total of 1173 students (intervention: n = 617; comparison school n = 556) completed both baseline and follow-up questionnaires. School start time was delayed by 15 min, from 7:45 a.m. to 8:00 a.m., in the intervention school. The comparison school maintained their regular SST at 7:55 a.m. Students' sleep-wake patterns, daytime sleepiness, and mental and behavioral aspects were assessed by validated questionnaires before and after the intervention. RESULTS: Students in the intervention school significantly delayed their weekday wake-up time (p < 0.001) and increased their total time in bed (p < 0.001) when compared to students in the comparison school. Both groups experienced a delay in their weekday bedtime. The students in the intervention school showed improved mental health [General Health Questionnaire (GHQ) score, p = 0.015], better prosocial behaviors (p = 0.009), better peer relationships (p < 0.001), greater attentiveness (p < 0.001), less emotional problems (p = 0.002), and less behavioral difficulties (p < 0.001) as measured by Strengths and Difficulties Questionnaire (SDQ). CONCLUSIONS: A modest delay (15 min) in school start time can increase adolescent sleep with corresponding improvement in mood and behaviors. Current findings have significant implications for education policy, suggesting that school administrators and policy makers should systematically consider delaying school start time to promote sleep and health among school-aged adolescents. CLINICAL TRIAL REGISTRATION: ChiCTR-TRC-12002798. The trial protocol can be accessed at: http://www.chictr.org/en/proj/show.aspx?proj=3955.