Junying Zhou

A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder

BACKGROUND Rapid eye movement sleep behavior disorder (RBD) is characterized by prominent dream-enacting behaviors, often resulting in sleep-related injuries. OBJECTIVES This study aimed to prospectively examine the treatment response of people with RBD treated with clonazepam, by quantitatively delineating the characteristic changes in the clinical and polysomnographic features, and to explore the factors associated with this response. METHODS Patients diagnosed with idiopathic RBD (iRBD) were consecutively recruited and invited to complete clinical and polysomnographic (PSG) assessments and self-administered questionnaires (including the modified REM Sleep Behavior Questionnaire, RBDQ-3M) before and after the initiation of treatment with clonazepam. RESULTS Thirty-nine iRBD patients (male: 74.4%, mean age at diagnosis: 68.3 ± 7.8 years) were recruited with a follow-up duration of 28.8 ± 13.3 months. Clonazepam was offered as the first-line treatment (starting dose: 0.43 ± 0.16 mg, range: 0.125-1.00; dose at follow-up: 0.98 ± 0.63 mg, range: 0.125-3). Treatment response, as defined by a complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or to bed partner, at follow-up was reported in 66.7% of the overall study subjects. Frequency of disturbing dreams with violent and frightening content and vigorous behavioral RBD symptoms was significantly reduced, while residual nocturnal symptoms and an increase in REM-related EMG activities were observed at follow-up. Less optimal treatment outcomes were found to be associated with the presence of comorbid obstructive sleep apnea and earlier onset of RBD. CONCLUSIONS Clonazepam differentially changes dream affect and content, as well as reduces vigorous verbal and motor behaviors. Residual RBD symptoms are common, despite treatment. Other more effective alternative or adjunctive interventions are needed for better clinical management of RBD.

A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness.

Excessive daytime sleepiness (EDS) and neurocognitive dysfunction are commonly observed in patients with obstructive sleep apnea (OSA), and these daytime functional deficits can be reversed partly or completely with treatment such as continuous positive airway pressure (CPAP). Although daytime sleepiness is a possible etiology for neurocognitive dysfunction in OSA patients, EDS is not universally present in all patients with OSA. The objective of this review is to summarize the relationship between neurocognitive function and EDS in OSA, as well as the difference in cognitive domains, improvement, and application of CPAP therapy between patients with and without EDS. Two authors independently searched PubMED/Medline, The Cochrane Library and Scopus through May 27, 2015. Sixty-five articles were included in this review. The literature demonstrated a wide range of neurocognitive deficits in OSA patients with EDS, but no more extensive and complex cognitive domains (eg, executive function) in patients without EDS. However, the current literature had very few studies with large sample sizes and extended follow-up that evaluated the effect of CPAP for OSA in patients with and without sleepiness. CPAP failed to improve cognitive dysfunction in OSA patients without EDS after short-term therapy. The evidence suggests that daytime sleepiness possibly relates to the domain and extent of cognitive impairments in OSA, and CPAP therapy has little effect on the improvement of cognitive deficits in OSA patients without EDS. We recommend that additional prospective studies be performed to further quantify the relationship between neurocognitive function in OSA patients with and without EDS.

Excessive Daytime Sleepiness Predicts Neurodegeneration in Idiopathic REM Sleep Behavior Disorder

Study Objectives To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD). Methods A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥14 were defined as having EDS. Demographic, clinical, and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model. Results After a mean follow-up of 5.8 years (SD = 4.3 years), 50 (27.9%) patients developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared to those without EDS (42.2 % vs. 23.1%, p = .01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37 to 4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movements during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinsons disease (PD) (adjusted HR = 3.55, 95% CI 1.59 to 7.89) but not dementia (adjusted HR = 1.48, 95% CI 0.44 to 4.97). Conclusions EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD.

Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China

OBJECTIVE Rapid eye movement (REM) sleep behavior disorder (RBD) has been considered a male-predominant parasomnia, and there is little comparative data on potential differences between males and females. Therefore, the aim of our study was to examine and characterize gender difference in RBD. METHODS Ninety patients diagnosed with RBD were consecutively recruited from a sleep medicine clinic. All patients were assessed by a RBD questionnaire and overnight video polysomnography. Demographic, clinical data, presence of dreams and dream-enacting behaviors, sleep parameters and electromyographic (EMG) activity were compared for male and female patients with RBD. RESULTS Females were significantly younger than males, both in the mean age of RBD onset (45.3 ± 19.3 vs. 56.2 ± 14.1; p = 0.027) and the mean age at diagnosis (50.4 ± 18.2 vs. 61.1 ± 14.1; p = 0.022). Secondary RBD was 21% in males and 44% in females (p = 0.021). Antidepressant use was more common among females (22%) than males (2%; p = 0.003). There was no significant gender difference in dream content (eg, violent and frightening dreams) of RBD patients. However, females had less dream-enacting behaviors, especially in movement related dreams and falling out of bed. Interestingly, no significant difference was found in the quantification of EMG activity during REM sleep between male and female patients. CONCLUSIONS We found significant gender differences in demographics, associated comorbidities, and dream-related behaviors in patients with RBD. Female RBD patients reported significantly less behavior during dreams, but there was no significant gender difference in EMG activity during REM sleep.

Help-seeking behaviors for insomnia in Hong Kong Chinese: a community-based study

OBJECTIVES To determine the prevalence and correlates of help-seeking behaviors for insomnia in Hong Kong Chinese middle-aged adults and their offspring. METHODS A total of 2231 middle-aged adults (54.2% females, mean age 45.8 years) and 2186 children and adolescents (51.9% females, mean age 13.4 years) completed a questionnaire on insomnia symptoms, daytime functioning, health condition and treatments sought for insomnia. RESULTS A total of 40% of adults and 10% of children and adolescents with insomnia reported having sought treatment for insomnia. Conventional Western medicine was the commonly preferred treatment in 33.3% of adults and 13.3% of children and adolescents who sought help for insomnia, while a higher proportion of individuals with insomnia (34.5% of adults and 26.7% of children and adolescents) sought help from complementary and alternative medicine (CAM) therapies. Female gender (odds ratio [OR] [95% confidence interval, CI] = 2.14 [1.01-4.53]), higher family income (≥15,000 HKD/month) (OR [95% CI] = 3.15 [1.27-6.34]), severity of insomnia (Insomnia Severity Index ≥14) (OR [95% CI] = 2.12 [1.10-4.12]), chronic medications (OR [95% CI] = 4.71 [2.27-9.79]), and psychiatric disorders (OR [95% CI] = 2.83 [1.01-7.96]) were associated with help-seeking behaviors in adults. Presence of morning headache was associated with help-seeking behaviors in children and adolescents (OR [95% CI] = 8.66 [1.72-43.70]). CONCLUSIONS It is uncommon for Hong Kong Chinese to seek help for insomnia, despite the high prevalence of insomnia. The significant unmet need argues for timely intervention to promote sleep-health literacy and to enhance the awareness and accessibility of evidence-based treatment for insomnia.

Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy.

OBJECTIVES To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. METHODS To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. RESULTS The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. CONCLUSION Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis.

Mortality and Its Risk Factors in Patients with Rapid Eye Movement Sleep Behavior Disorder.

STUDY OBJECTIVES To determine the mortality and its risk factors in patients with rapid eye movement (REM) sleep behavior disorder (RBD). METHODS A total of 205 consecutive patients with video-polysomnography confirmed RBD (mean age = 66.4 ± 10.0 y, 78.5% males) were recruited. Medical records and death status were systematically reviewed in the computerized records of the health care system. Standardized mortality ratio (SMR) was used to calculate the risk ratio of mortality in RBD with reference to the general population. RESULTS Forty-three patients (21.0%) died over a mean follow-up period of 7.1 ± 4.5 y. The SMR was not increased in the overall sample, SMR (95% confidence interval [CI]) = 1.00 (0.73-1.33). However, SMR (95% CI) increased to 1.80 (1.21-2.58) and 1.75 (1.11-2.63) for RBD patients in whom neurodegenerative diseases and dementia, respectively, eventually developed. In the Cox regression model, mortality risk was significantly associated with age (hazard ratio [HR] = 1.05; 95% CI, 1.01-1.10), living alone (HR = 2.04; 95% CI, 1.39-2.99), chronic obstructive pulmonary disease (HR = 3.38; 95% CI, 1.21-9.46), cancer (HR = 10.09; 95% CI, 2.65-38.42), periodic limb movements during sleep (HR = 3.06; 95% CI, 1.50-6.24), and development of neurodegenerative diseases (HR = 2.84; 95% CI, 1.47-5.45) and dementia (HR = 2.66; 95% CI, 1.39-5.08). CONCLUSIONS Patients with RBD have a higher mortality rate than the general population only if neurodegenerative diseases develop. Several risk factors on clinical and sleep aspects are associated with mortality in RBD patients. Our findings underscore the necessity of timely neuroprotective interventions in the early phase of RBD before the development of neurodegenerative diseases.

Family conflict and lower morning cortisol in adolescents and adults: modulation of puberty.

We aimed to explore the association between family conflict and HPA axis activity, especially with respect to the potential modulating effect of puberty. A total of 205 adolescents and 244 adult parents were recruited. Family conflict was assessed by the family conflict subscale of the Family Environmental Scale and serial salivary cortisol was measured in all participants. A marginally lower AUCg at 30 minutes after wake up in the morning and a significant lower AUCg at 60 minutes and 90 minutes in adult parents with high family conflict was found when compared to those with low family conflict. In adolescents, there were significant interaction effects between pubertal status and family conflict on AUCg (interaction p values <0.05). Among the adolescents with low family conflict, those at late/post pubertal status had higher AUCg than their pre/early pubertal counterparts but this difference was not observed in the adolescents with high family conflict. Adverse family environment is associated with HPA axis dysfunction in adults and late/post pubertal adolescents and pubertal maturation plays a critical role in modulating the association between family environment and HPA axis function.