Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*

The parabrachial nucleus (PBN) integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing, emotion, and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem. However, the precise identity and function of distinct PBN subpopulations are still largely unknown. Here, we leveraged molecular characterization, retrograde tracing, optogenetics, chemogenetics, and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain, rather than the medulla. Their activation induces freezing and anxiety-like behaviors, which in turn result in tachypnea. In addition, optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture. We propose that these neurons comprise a PBN subpopulation with specific gene expression, connectivity, and function, which play essential roles in behavioral and physiological regulation.
Parabrachial Nucleus/physiology* ; Wakefulness/physiology* ; Neurons/physiology* ; Emotions ; Sleep

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

Sleep is an extremely important physiological state to maintain human life. Sleep disorders can not only cause anxiety and depression, but also induce multi-system diseases that seriously affect brain function and physical health. The neuroinflammation is a key pathological process after sleep disorders, which can induce a series of nervous system diseases. In recent years, the role of microglia activation in neuroinflammation has been paid more and more attention and become a research hotspot in this field. The imbalance of the central microenvironment after sleep disorders leads to changes in the activation and polarization of microglia, which triggers neuroinflammatory response. The activation and polarization of microglia in the sleep disorders are regulated by multiple signaling pathways and complex molecular mechanisms. This paper summarizes five signaling pathways of microglia activation in central inflammation induced by sleep disorders, including P2X7 receptor (P2X7R), p38MAPK, Toll-like receptor 4 (TLR4)/NF-κB, JAK/STAT, and α7 nicotinic acetylcholine receptor (α7-nAChR) pathways, in order to provide reference for further research and clinical treatment targets selection of sleep disorders.
Humans ; Neuroinflammatory Diseases ; Microglia/metabolism* ; Signal Transduction/physiology* ; NF-kappa B/metabolism* ; Inflammation/metabolism* ; Sleep Wake Disorders/metabolism*

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

Neural oscillations reflect synchronized activities of neuronal ensembles in central nervous system. In the hippocampus, thalamus, neocortex and other brain subregions, neural oscillation can be detected and plays a crucial role in many complicated cognitive processes. Decoupling and damaging of neural oscillation play a key role in the induction of severe cognition deficits in many psychiatric disorders. In this review, we summarize research advances in the underlying mechanisms and physiological functions of neural oscillations. We also discuss the abnormal changes of sharp wave-ripple, gamma oscillation and sleep spindle oscillation in major depressive disorder, schizophrenia and Alzheimer's disease, etc. Finally, the application potential of neural oscillations as clinical diagnosis and treatment targets is evaluated and prospected.
Depressive Disorder, Major ; Hippocampus/physiology* ; Humans ; Neurons ; Sleep/physiology*

Objective: To explore the correlation between sleep status and frailty in adults aged 30-79 years in China, and explore the potential effect modification of general and central obesity. Methods: Based on the baseline data of the China Kadoorie Biobank, we used multinomial logistic regression to analyze the correlation between long and short sleep duration, insomnia disorder, snoring, and unhealthy sleep score with risks of pre-frailty and frailty. Both overall and obesity-stratified analyses were performed. Result: Among the 512 724 participants, 2.3% had frailty and 40.1% had pre-frailty. There was a U-shaped relationship between sleep duration and frailty score. Short (OR=1.21, 95%CI: 1.19-1.23) or long sleep duration (OR=1.19, 95%CI: 1.17-1.21), insomnia disorder (OR=2.09, 95%CI: 2.02-2.17), and snoring (OR=1.61, 95%CI: 1.59-1.63) were all positively correlated with pre-frailty, and dose-response relationships were observed between unhealthy sleep score and pre-frailty (P for trend<0.001), with OR values of 1.46 (1.44-1.48), 1.97 (1.93-2.00) and 3.43 (3.21-3.67) respectively for those having unhealthy sleep score of 1 to 3. These sleep problems were also positively correlated with frailty. Compared with the overweight or obesity group, stronger relationships were observed between short sleep duration and frailty or pre-frailty and between insomnia disorder and pre-frailty, while the relationships between snoring and frailty and pre-frailty were weaker in the participants with normal weight (P for interaction <0.007 for all). We also observed similar effect modification by central obesity. Conclusion: Long or short sleep duration, insomnia disorder, snoring and higher unhealthy sleep scores were positively correlated with pre-frailty or frailty, general and central obesity status could modify the relationships.
Adult ; China/epidemiology* ; Frailty/epidemiology* ; Humans ; Obesity ; Obesity, Abdominal ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Sleep Wake Disorders ; Snoring/epidemiology*

OBJECTIVE: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia. METHODS: Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO₁₅) and Shen (CO₁₀) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately. RESULTS: After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01). CONCLUSION The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.
Heart Rate/physiology* ; Humans ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/therapy* ; Vagus Nerve ; Vagus Nerve Stimulation

OBJECTIVE: To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). METHODS: A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO₁₅) and Shen (CO₁₀) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. RESULTS: After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). CONCLUSION taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.
Brain/physiology* ; Default Mode Network ; Humans ; Magnetic Resonance Imaging/methods* ; Sleep Initiation and Maintenance Disorders/therapy* ; Vagus Nerve ; Vagus Nerve Stimulation/methods*

INTRODUCTION: In a subset of adults with non-rapid eye movement (NREM) parasomnias, clinical variants might be violent in nature and can potentially result in unintentional but considerable harm. As such, there is substantial interest on the forensic ramifications of these sleep behaviours. METHODS: This review examined the diagnostic criteria for parasomnias established in the context of international classification systems; medicolegal case reports; legal frameworks; and court cases in and outside of Singapore, to provide an overview of the implications of NREM parasomnias. RESULTS: Violent or injurious behaviours that occurred in the context of somnambulism, otherwise known as sleepwalking, have challenged traditional legal theories of criminal culpability. Yet little has changed in the application of sleep science to criminal responsibility. In Singapore, the defence of somnambulism has hitherto not been directly raised. Nonetheless, sleep medicine practitioners may increasingly be requested to render their opinions on legal issues pertaining to violent or injurious behaviours allegedly arising during sleep. Although the understanding of NREM parasomnias has improved, there is still a dearth of evidence to support both medical and legal decisions in this area. CONCLUSION NREM parasomnias come with disquieting legal and forensic implications for adjudicating criminal responsibility. There is a need to critically examine legal perspectives on behaviours occurring during sleep. More reliable empirical studies investigating the pathophysiology of NREM parasomnias can offer clearer diagnostic guidelines and address complex behaviours of NREM that often come with medicolegal implications.
Adult ; Humans ; Parasomnias/diagnosis* ; Singapore ; Sleep/physiology* ; Somnambulism/diagnosis*