Effect of bright-light therapy on depression and anxiety of a patient with Alzheimer’s disease combined with sleep disorder:A case report

BACKGROUND Alzheimer’s disease(AD)is a common type of dementia due to neuronal impairment.In addition,psychobehavioral symptoms including severe sleep disorders,depression and anxiety can occur in most patients with AD.CASE SUMMARY We report a case of a 68-year-old woman with a 2-year history of AD.She initially presented with memory loss,progressively more severe,leading to a depressive and anxious status.The clinical symptoms also included severe sleep disturbances.Considering the age and health state of the patient,a non-pharmacological treatment of bright light therapy was used to improve her sleep quality.The treatment was provided for 30 minutes twice a day,during 8:30 am to 9:00 am and 16:30 pm to 17:00 pm.After 4 weeks of therapy,the sleep quality notably improved,with a marked decrease in daytime sleep,increase in nighttime sleep,and disappearance of nocturnal activity.The depression and anxiety were also suppressed significantly.CONCLUSION This case report suggested that bright light therapy can have a positive effect on sleep quality in elderly patients with AD and can be used as an effective and safe non-pharmacological treatment.

Sleep disorders in Alzheimer’s disease:the predictive roles and potential mechanisms

Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-βand tau in patients with Alzheimer’s disease.At present,sleep disorders are considered as a risk factor for,and may be a predictor of,Alzheimer’s disease development.Given that sleep disorders are encountered in other types of dementia and psychiatric conditions,sleep-related biomarkers to predict Alzheimer’s disease need to have high specificity and sensitivity.Here,we summarize the major Alzheimer’s disease-specific sleep changes,including abnormal non-rapid eye movement sleep,sleep fragmentation,and sleep-disordered breathing,and describe their ability to predict the onset of Alzheimer’s disease at its earliest stages.Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer’s disease.This paper therefore explores some potential mechanisms that may contribute to sleep disorders,including dysregulation of the orexinergic,glutamatergic,andγ-aminobutyric acid systems and the circadian rhythm,together with amyloid-βaccumulation.This review could provide a theoretical basis for the development of drugs to treat Alzheimer’s disease based on sleep disorders in future work.

Sleep deprivation increase the expression of inducible heat shock protein 70 in rat gastric mucosa

AIM: To investigate if sleep deprivation is able to increase the expression of inducible heat shock protein 70 in gastric mucosa and its possible role in mucosal defense. METHODS: Rats for sleep disruption were placed inside a computerized rotating drum, gastric mucosa was taken from rats with 1, 3 and 7d sleep deprivation. RT-PCR, immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70. Ethanol (500mL.L(-1), i.g.) was used to induce gastric mucosa damage. RESULTS: RT-PCR, Western blotting and immunostaining confirmed that the sleep deprivation as a stress resulted in significantly greater expression of inducible heat shock protein 70 in gastric mucosa of rats. After the 500mL.L(-1) ethanol challenge, the ulcer area found in the rats with 7d sleep deprivation (19.15 +/- 4.2)mm(2) was significantly lower (P【0.01) than the corresponding control (53.7 +/- 8.1) mm(2). CONCLUSION: Sleep deprivation as a stress, in addition to lowering the gastric mucosal barrier, is able to stimulate the expression of inducible heat shock protein 70 in gastric mucosa of rats, the heat shock protein 70 may play an important role in gastric mucosal protection.

Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder(iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients(male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls(male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume(GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital(approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry(ISRCTN18238599).

Dementia in military and veteran populations:a review of risk factors—traumatic brain injury,post-traumatic stress disorder,deployment,and sleep

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia.Traumatic brain injury(TBI)and post-traumatic stress disorder(PTSD)have a higher prevalence in this group in comparison to the civilian population.By delving into the individual relationships between TBI and dementia,and PTSD and dementia,we are able to better explore dementia in the military and veteran populations.While there are some inconsistencies in results,the TBI-dementia association has become more widely accepted.Moderate-tosevere TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease.A correlation between PTSD and dementia has been established,however,whether or not it is a causal relationship remains unclear.Factors such as blast,combat and chemical exposure may occur during a deployment,along with TBI and/or PTSD diagnosis,and can impact the risk of dementia.However,there is a lack of literature exploring the direct effects of deployment on dementia risk.Sleep problems have been observed to occur in those following TBI,PTSD and deployment.Poor sleep has been associated with possible dementia risk.Although limited studies have focused on the link between sleep and dementia in military and veteran populations,sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors.This review aims to inform of various risk factors to the cognitive health of military members and veterans:TBI,PTSD,deployment,and sleep.

How non-rapid eye movement sleep and Alzheimer pathology are linked

Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles.Research attempts to identify characteristic factors that are associated with the presence of the AD pathology on the one hand and that increase the risk of developing AD on the other.Changes in non-rapid eye movement(NREM)sleep may meet both requirements for various reasons.First,NREM-sleep is important for optimal memory function.In addition,studies report that the presence of AD pathology is associated with NREM-sleep changes.Finally,more and more results appear to suggest that sleep problems are not only a symptom of AD but can also increase the risk of AD.Several of these studies suggest that it is primarily a lack of NREM-sleep that is responsible for this increased risk.However,the majority investigated sleep only through subjective reporting,as a result of which NREMsleep could not be analyzed separately.The aim of this literature study is therefore to present the results of the studies that relate the AD pathology and NREM-sleep(registered by electroencephalography).Furthermore,we try to evaluate whether NREM-sleep analysis could be used to support the diagnosis of AD and whether NREM-sleep deficiency could be a causal factor in the development of AD.

Clinical Characteristics of Sleep Disorders in Patients with Parkinson's Disease

In order to investigate the sleep quality and influencing factors in patients with Parkinson＇s disease（PD）, 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index（PSQI）, and the Epworth Sleepiness Scale（ESS）. It was found that poor sleep quality（77.11%） and excessive daytime sleepiness（32.34%） were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency（SE） was significantly decreased（P〈0.01）, and sleep latency（SL） and the arousal index（AI） were increased（P〈0.05） in the PD group as compared with those in the control group. SE and total sleep time（TST） were positively correlated with the Hoehn and Yahr（H＆Y） stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group（P〈0.05）. Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

Melatonin’s actions are not limited to sleep

Melatonin is widely available as a supplement,usually for sleep disorders.The consumption of melatonin supplements has increased considerably in recent years.An overlooked aspect of melatonin’s administration is the resulting increase in prolactin secretion,via its action on hypothalamic dopaminergic neurons.We believe that since the effect of melatonin on prolactin is tangible,the laboratory finding of hyperprolactinemia could be encountered more often,given the increase in melatonin’s use.This is an issue that merits further study.

Lack of Association between Impulse Control Disorders and REM Sleep Behavior Disorder in Patients with Parkinson’s Disease

Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The aim of this study is to analyze the association between these two non-motor symptoms. Methods: Consecutive subjects with Parkinson’s disease attending the Movement Disorders Outpatient Clinic were included. The presence of ICDs was assessed using the Questionnaire for Impulse Control Disorders Rating Scale. RBD was diagnosed by an overnight, single night polysomnography. Results: Fifty-five consecutive subjects with Parkinson’s disease were included. The prevalence of ICDs and related behaviors was 23.6% (ICD in 14.5% and related behaviors in 9.1%). RBD was diagnosed in 47.2% of the patients. No differences were found in the frequency of ICDs and related behaviors when comparing subjects with and without RBD (23% versus 24.1%, p = 0.926, respectively). Conclusion: No association between the presence of RBD and the frequency of ICDs in subjects with Parkinson’s disease was found.

Sleep Disturbance in Parkinson’s Disease Varies with Age of Onset and Family History

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.

S6B-3 Intracerebroventricular Streptozocin-Induced Alzheimer’s Disease-Like Sleep Disorders:Role of the GABAergic System in the Parabrachial Complex

Aim:Sleep disorders are common in Alzheimer’s disease(AD)and assumed to directly influence cognitive function and progression of the disease.The present study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular administration of streptozocin,and we assessed the possible underlying mechanisms.Methods:The cognition ability of rats was assessed by Morris water maze(MWM)trails.Sleep parameters were analyzed by electroencephalographic(EEG)and electromyographic(EMG)recordings.The neuronal activity in sleep-wake regulating brain areas was evaluated by double-staining immunohistochemistry test.High performance liquid chromatograph-electrochemical detection(HPLC-ECD)was used for the detection of neurotransmitters.Results:On day 14 after STZ injection,the rats exhibited sleep disorders that are similar to those in AD patients as evidenced by significant increase in wakefulness and decrease in rapid-eye movement sleep(REMS)and non-REMS.The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ rats.In the ventrolateral preoptic nucleus(VLPO),the activity ofγ-aminobutyric acid(GABA)neurons was suppressed.In the arousal-driving parabrachial nucleus(PBN),GABAergic activity was suppressed,whereas glutamatergic activity was promoted.The neurotransmitter analysis revealed a reduction of GABA in the VLPO and PBN and elevations of glutamate in the PBN.A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar sleep disorder pattern as in STZ rats.Furthermore,a microinjection of GABA in the PBN improved sleep disorders induced by STZ.Conclusion:These results suggest that the reduction of GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders induced by STZ.Our novel findings encourage further study aimed at investigating the new mechanisms of sleep regulation in sporadic AD.

Relationship between Authoritative Parenting Style and Preschool Children’s Emotion Regulation:A Moderated Mediation Model

An authoritative parenting style has been shown to promote children’s emotion regulation in European-American family studies.However,little is known about how sleep problems and the child’s sibling status in Chinese families affect this relationship.Based on family system theory,this study attempts to better understand the relationship between authoritative parenting style and emotion regulation.Mothers of preschool children in Chinese kindergartens completed questionnaires about their children’s sleep habits,their authoritative parenting styles,and children’s emotion regulation.A total of 531 children participated in this study.Results showed that authoritative parenting was positively associated with emotional regulation.Sleep problems mediated the effects of authoritative parenting style on emotion regulation.The child’s sibling status moderated the mediating effects of sleep problems in authoritative parenting and emotion regulation relationships.Specifically,the relationship between the authoritative parenting style and sleep problems was significant for only children,while birth order had no significant influence on the authoritative parenting style and sleep problems in two-child families.These findings suggest that a lowauthoritative parenting style predicts low emotion regulation through sleep problems,and this depends on the child’s sibling status,indicating that children without siblings may impair emotion regulation due to increased sleep problems.

观察基于Watson人性照顾理论的干预对重症肺炎合并呼吸衰竭患者的应用效果

目的:观察基于Watson人性照顾理论的干预对重症肺炎合并呼吸衰竭患者的应用效果。方法:选取2021年6月至2023年6月泉州市第一医院呼吸与危重症医学科收治的重症肺炎合并呼吸衰竭患者94例作为研究对象,按照随机数字表法分为对照组和观察组,每组47例。对照组给予常规护理干预,观察组在对照组基础上给予Watson人性照顾理论的干预。采用匹兹堡睡眠质量指数量表(PSQI)比较2组患者干预前后睡眠质量的变化,采用阿森斯失眠量表(AIS)评估2组患者干预前后失眠的改善效果,并通过2组患者护理后的呼吸困难缓解时间、机械通气时间、重症监护室住院时间,以判断恢复情况。结果:干预后,观察组患者PSQI评分、AIS评分均显著低于对照组,观察组呼吸困难缓解时间、机械通气时间及重症监护室住院时间均显著短于对照组,差异均有统计学意义(均P<0.05)。结论:对重症肺炎合并呼吸衰竭患者应用基于Watson人性照顾理论的护理干预可有效改善其睡眠质量,促进病情恢复,值得临床推广应用。

Transcranial Direct Current Stimulation: Effects on Motor and Non-Motor Symptoms of Parkinson’s Disease

Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson’s disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2 mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

神经肽S对睡眠觉醒的调节

新发现神经肽S （NPS）及其受体（NPSR）构成一新的内源性神经调节系统,NPS-NPSR系统被认为是中枢新的觉醒系统参与睡眠觉醒周期的生理与病理过程.近期研究证明侧脑室注射NPS引起大鼠脑电高频（14.5～60 Hz）活动增强为特征的觉醒时间增加,同时抑制脑电δ波和θ波为特征的慢波睡眠（SWS）和异相睡眠或称为快动眼睡眠（PS/REMS）;NPSR拮抗剂[D-Cys（tBu）5] NPS引起大鼠觉醒减少,SWS增加,而不影响PS/REMS. NPSR rs324981单核苷酸多态性和Asn/Ile 107 NPSR多态性与人类的生理性睡眠调节密切相关.机制研究揭示下丘脑结节乳头体核（TMN）91.5％组胺能神经元表达NPSR,TMN注射0.1 nmoL NPS引起大鼠觉醒时间,比侧脑室注射1nmoL NPS引起大鼠觉醒时间显著延长,该作用可分别被NPSR、组胺受体H1R和组胺受体H2R拮抗剂所拮抗,提示NPS神经元投射TMN经NPSR介导激活组胺能神经元是NPS-NPSR调节睡眠觉醒的重要通路.另外,证据表明NPS抗焦虑与抑郁引起睡眠紊乱.为此,揭示NPS能神经元投射途径、作用靶点与突触后神经元作用模式,发现NPSR高效激动剂及拮抗剂将成为今后工作重点.

大鼠中枢神经系统中神经肽S的表达及对睡眠功能的影响

目的研究剥夺睡眠大鼠的神经肽S表达水平,探讨其与睡眠的关系。方法共对27只大鼠进行实验,分别为CC组(正常对照组)、TC组(环境对照组)及SD组(睡眠对照组),在相应的环境中饲养1d、3d和5d,对大鼠下丘脑中神经肽S的表达水平进行研究并比较。结果大鼠睡眠剥夺后出现体质量降低、皮毛蓬乱、潮湿无光滑。部分大鼠尾巴和爪子出现磨损,大鼠情绪烦躁不安,较容易发怒且具有较强的攻击性,这些表现在睡眠剥夺5d后表现得更加明显;CC组和TC组在实验第1天、第3天和第5天的下丘脑神经肽S mRNA的表达水平差异无统计学意义(P>0.05);SD组第3天和第5天下丘脑神经肽S mRNA的表达水平均高于第1天,差异具有统计学意义(P<0.05);SD组第3天和第5天下丘脑神经肽S mRNA的表达水平均高于CC组和TC组,差异具有统计学意义(P<0.05)。结论神经肽S可能具有促进觉醒的作用,对人体的睡眠与觉醒产生一定的调节作用,可能与失眠等多种疾病的发生具有密切的相关性,值得更加深入的研究。

无线传感器网络S-MAC协议能量有效性改进

针对无线传感器网络中节点能量受限的特点,对目前典型的无线传感器网络信道接入协议(S-MAC)的休眠机制进行了改进。改进后的协议(ES-MAC)根据传感/转发事件发生间隔的变化而自适应调整各节点的休眠时长以节省空闲监听的能量消耗,从而延长整个网络的生存时间。仿真结果表明,在传感/转发事件发生间隔较长的情况下,改进后的协议能够很好地工作,并提高了原协议的能量有效性。

快速眼球运动睡眠剥夺对大鼠下丘脑背内侧核神经肽S表达的影响

目的探讨快速眼球运动(rapid eye movement,REM)睡眠剥夺后大鼠下丘脑背内侧核神经肽S(neuropeptide S,NPS)表达的变化。方法24只大鼠随机均分为正常对照(CC)组、环境对照(TC)组、REM睡眠剥夺(SD)组,采用改良多平台睡眠剥夺法建立大鼠REM睡眠剥夺模型,运用免疫组织化学分析法及原位杂交法观察大鼠经3dREM睡眠剥夺后下丘脑内NPS蛋白及mRNA的表达变化。结果NPS蛋白及mRNA的表达在CC组和TC组没有显著差异。REM睡眠剥夺后,大鼠下丘脑背内侧核内的NPS蛋白及mRNA表达上调,SD组下丘脑背内侧核内NPS蛋白及mRNA阳性细胞数分别为(27.86±2.47)和(25.75±2.12),较CC组(16.75±2.12和19.63±1.85)、TC组(18.60±1.60和18.50±1.69)升高(P<0.05)。结论REM睡眠剥夺后下丘脑内觉醒相关区域NPS表达增加,说明当REM睡眠减少时机体会主动调节NPS的分泌,提示NPS与睡眠觉醒的调节机制有关。

基于扩展Infomax与DOST的多导联睡眠脑电伪迹去除方法研究

对多导联脑电信号(EEG)的预处理对于睡眠疾病的检测、预防和治疗有着重要的意义,传统的S变换法在处理多导联EEG信号时在伪迹自动识别、计算复杂度和阈值选取这三方面存有不足,影响了该方法的应用效果。为了提高该方法的应用效果,采用一种扩展Infomax与离散正交S变换结合的伪迹去除方法(DOSTIN),根据分形维数法实现伪迹识别,利用最大类间方差法使阈值的选取避免了过度去噪造成的有用信号损失。采用麻省理工的公开数据集验证去噪后的效果,结果表明DOSTIN法在保证去噪效果的同时,比ICA与S变换相结合方法的计算复杂度降低了30%,证明该方法在多导联信号去噪方面具备可行性。