Zhengqing Zhao

Neuropeptide S mitigates spatial memory impairment induced by rapid eye movement sleep deprivation in rats.

Rapid eye movement (REM) sleep deprivation causes learning and memory deficits. Neuropeptide S, a newly discovered neuropeptide, has been shown to regulate arousal, anxiety, and may enhance long-term memory formation and spatial memory. However, it is unknown whether neuropeptide S could improve the REM sleep deprivation-induced memory impairment. Here, we report that 72-h REM sleep deprivation in rats resulted in spatial memory impairment and reduced phosphorylation level of cAMP-response element binding protein in the hippocampus, both of which were reversed by central administration of neuropeptide S. The results suggest that neuropeptide S mitigates spatial memory impairment in rats induced by 72-h REM sleep deprivation, possibly through activating cAMP-response element binding protein phosphorylation in the hippocampus.

Symptoms and occurrences of narcolepsy: a retrospective study of 162 patients during a 10-year period in eastern China.

OBJECTIVE Our study was designed to assess symptomatology and occurrences of narcolepsy in eastern China between 2003 and 2012. Herein we report the substantial changes in the occurrence and clinical features of narcolepsy over the last decade in China. METHODS We performed a retrospective analysis of 162 Han Chinese patients with narcolepsy at Changzheng Hospital, Shanghai, China. Clinical histories and precipitating factors were recorded, in addition to narcolepsy and H1N1 winter flu pandemic (pH1N1) occurrences at Changzheng Hospital. The occurrences also were compared between the Changzheng Hospital and the Peoples Hospital, Beijing, China. RESULTS In our sample, narcolepsy occurred 1.73 times more frequently in men than in women. Most of the participants were children, which peaked to 91% in 2010. Excessive daytime sleepiness (EDS), disrupted nocturnal sleep, cataplexy, and weight gain were the four major symptoms. We found that 40% of patients had identifiable precipitating factors. The occurrence of narcolepsy in 2010 showed an approximate three-fold difference from the baseline levels at the Changzheng Hospital, which showed positive relationships with occurrences of pH1N1 in Shanghai and the occurrence of narcolepsy at the Peoples Hospital. CONCLUSIONS Our findings show the interactive effects of geography and H1N1 disease in relation to narcolepsy in Han Chinese populations, and strengthen the theoretic hypothesis that immune and mental factors facilitate the onset of narcolepsy.

Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

Sleep disturbances (SD) accelerate the progression of Alzheimers disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

Interleukin-1β Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Sleep alleviates Alzheimer’s disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33–14.10, p = 0.015). Compared to the IL-1β CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13–2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.

Metabolic abnormality of pontine tegmentum in patients with REM sleep behavior disorder analyzed using magnetic resonance spectroscopy.

OBJECTIVES We aimed to evaluate the metabolism differences in pontine tegmentum among patients with idiopathic RBD (iRBD), secondary RBD (sRBD) and healthy control groups using magnetic resonance spectroscopy ((1)H-MRS) and whether metabolic changes are correlated with age in patients with RBD. PATIENTS AND METHODS The iRBD, sRBD, and control groups were composed of 18, 26, and 29 patients, respectively. All participants underwent magnetic resonance imaging (MRI) and (1)H-MRS detection at 17:00 for approximately 15min. All NAA/Cr, Cho/Cr and NAA/Cho ratios were automatically generated using FuncTool and the correlation between metabolism and age was analyzed by Pearsons correlation analysis. RESULTS Significant difference in NAA/Cr ratio was found between the sRBD group and the other groups (p<0.05). Significant difference in NAA/Cho ratio was found among all groups (p<0.05). Cho/Cr ratio remarkably increased in the control group (p<0.05) compared with the other groups. NAA/Cr ratio had an adverse correlation with age in the control, iRBD, and sRBD groups (r=-0.822, p=0.000 vs r=-0.663, p=0.003 vs r=-0.583, p=0.002). However, there was no correlation between participants age and Cho/Cr (r=-0.054, p=0.651) or NAA/Cho (r=0.029, p=0.805). CONCLUSION Neurons in the sRBD group were lost or damaged; however, this damage was not obvious in the iRBD group. Nevertheless, NAA and Cho levels were reduced in the local nerve cells of both RBD groups; these changes might indicate the sensitive pathogenic areas among patients with RBD.

Effect of low-intensity pure tone auditory stimulation on patients with rapid eye movement sleep behavior disorder

Objective: This study aimed to investigate the influence of low-intensity pure tone auditory stimulation on patients with rapid eye movement (REM), sleep behavior disorder (RBD), and attempt to identify a new method of RBD intervention. Methods: Patients diagnosed with idiopathic RBD (iRBD) or symptomatic RBD (sRBD) were given auditory stimulation of low-intensity pure tones during their REM sleep. Sleep parameters including sleep process, sleep architecture as well as eye movements (EMs) frequency, and amplitude were recorded by polysomnography monitoring at pre-, intra-, and post-stimulation. Results: Thirteen iRBD and 18 sRBD patients completed this study. Auditory stimulation significantly reduced the EMs frequency and amplitude in iRBD and sRBD patients (p < 0.05). In the iRBD group, the intra-stimulated FSL increased significantly than the pre-stimulated FSL (p < 0.05). After stimulation, patients had similar sleep latency (FSL), rapid eye movement sleep latency (RSL) and periodic limb movements in sleep (PLMS) compared with control. In the sRBD group, the intra-stimulated total sleep time, sleep efficiency was significantly increased, whereas the RSL and PLMS were significantly reduced compared with the pre-stimulated ones (all p < 0.05). The sRBD patients had similar time in bed, FSL and RBD episodes compared with control (all p < 0.05) in spite of significant difference before stimulation (all p < 0.05). However, the sleep architecture was not influenced by the stimulation despite the decrease in N3% in iRBD group (p < 0.05). Conclusion: Low-intensity pure tone auditory stimulation may be a potentially effective intervention for RBD, especially for sRBD.