Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

BACKGROUND Patients with schizophrenia may have various disease manifestations,most of which gradually tend toward incurable chronic decline,leading to mental disability.The basic symptoms of the disease can impair social function,whereas long-term hospitalization produces hospitalization syndrome,causing serious damage to social function.AIM To investigate the effects of Computerized Cognitive Remediation Therapy(CCRT)on cognitive and social functioning in patients with chronic schizophrenia.METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed.They were divided into an intervention group(60 cases treated with CCRT combined with conventional medication)and a control group(60 cases treated with conventional medication).After treatment,effects on cognitive function and social roles were observed in both groups.The Positive and Negative Syndrome Scale(PANSS)was used to assess the patients'psychiatric symptoms.The Wisconsin Card Sorting Test(WCST)was used to assess the patients'cognitive functioning,and the Social Functioning Scale for Psychiatric Inpatients(SSPI)was used to assess the social functioning of the inpatient psychiatric patients.RESULTS No significant differences were observed in the PANSS,WCST,and SSPI intergroup scores before treatment(P>0.05).After 2,4,and 6 wk of therapy,general psychopathological factors,positive symptoms,negative symptoms,and total PANSS scores of PANSS in the intervention group were lower than in the control group(P<0.05).After 2,4,and 6 wk of treatment,the number of false responses,number of persistent bugs,and total responses in the WCST were significantly lower in the intervention group than in the control group(P<0.05),and the amount of completed classification was significantly higher than in the control group(P<0.05).After 2,4,and 6 wk of therapy,the SSPI scores were significantly greater than those of the controls(P<0.05).After 6 wk of treatment,the efficacy rates of the control and intervention groups were 81.67%and 91.67%,respectively.The curative effect in the intervention group was significantly higher than that in the control group(P<0.05).CONCLUSION CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.

Abnormalities of electroencephalography microstates in patients with depression and their association with cognitive function

BACKGROUND A growing number of recent studies have explored underlying activity in the brain by measuring electroencephalography(EEG)in people with depression.However,the consistency of findings on EEG microstates in patients with depression is poor,and few studies have reported the relationship between EEG microstates,cognitive scales,and depression severity scales.AIM To investigate the EEG microstate characteristics of patients with depression and their association with cognitive functions.METHODS A total of 24 patients diagnosed with depression and 32 healthy controls were included in this study using the Structured Clinical Interview for Disease for The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.We collected information relating to demographic and clinical characteristics,as well as data from the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS;Chinese version)and EEG.RESULTS Compared with the controls,the duration,occurrence,and contribution of microstate C were significantly higher[depression(DEP):Duration 84.58±24.35,occurrence 3.72±0.56,contribution 30.39±8.59;CON:Duration 72.77±10.23,occurrence 3.41±0.36,contribution 24.46±4.66;Duration F=6.02,P=0.049;Occurrence F=6.19,P=0.049;Contribution F=10.82,P=0.011]while the duration,occurrence,and contribution of microstate D were significantly lower(DEP:Duration 70.00±15.92,occurrence 3.18±0.71,contribution 22.48±8.12;CON:Duration 85.46±10.23,occurrence 3.54±0.41,contribution 28.25±5.85;Duration F=19.18,P<0.001;Occurrence F=5.79,P=0.050;Contribution F=9.41,P=0.013)in patients with depression.A positive correlation was observed between the visuospatial/constructional scores of the RBANS scale and the transition probability of microstate class C to B(r=0.405,P=0.049).CONCLUSION EEG microstate,especially C and D,is a possible biomarker in depression.Patients with depression had a more frequent transition from microstate C to B,which may relate to more negative rumination and visual processing.

Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review

Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.

Age-related differences in long-term potentiation-like plasticity and shortlatency afferent inhibition and their association with cognitive function

Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticity might represent a potential neurophysiological marker for language function.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Associations between residence and cognitive function among Chinese older adults: the mediating role of leisure activity

Background:Cognitive function is a current research hotspot,residence may be related to differences in cognitive function,and the mediating role of leisure activities are limited in Chinese research.This study used leisure activities as a mediating variable to investigate the mediating role of leisure activity between place of residence(city-town-rural)and cognitive function among Chinese older,this is where the innovation of the article comes in.Methods:Using cross-sectional data from the 2018 Chinese Longitudinal Healthy Longevity Survey,Pearson correlation analyses were employed to examine the relationships among various indicators.Mediation analyses were conducted using the SPSS PROCESS macro program,version 3.5,written by Hayes,to explore the mediating effects of leisure activity between place of residence and cognitive function in older adults.Results:A total of 10955 older adults were included in this study,with a mean age of(84.23±11.57)years.Among them,2739(24.8%)lived in the city,3627(33.1%)in town,and 4615(42.1%)in rural areas;their leisure activity score was(5.34±3.77),and their cognitive function score was(24.69±6.65).Place of residence,leisure activities,and cognitive function were significantly correlated(P<0.01).Using city as a reference,place of residence is negatively associated with cognitive function,and place of residence not only had a direct effect on cognitive function in older adults:town-cognitive function(effect=–0.399;95%confidence interval(CI)=(–0.685,–0.113));rural-cognitive function(effect=–0.42;95%CI=(–0.698,–0.141)).There were also indirect effects on cognitive function through the pathway of leisure activity:town-leisure activity-cognitive function(effect=–0.17;95%CI=(–0.246,–0.1)),rural-leisure activity-cognitive function(effect=–0.199;95%CI=(–0.272,–0.13)).Conclusion:Leisure activities play a partially mediating role between the impact of place of residence and cognitive function in Chinese older adults,and it is vital to pay attention to the impact of place of residence on the cognitive function of older adults in various aspects,and to increase the participation rate of older adults in leisure activities,which is beneficial to the prevention of cognitive decline and the protection of older adult’s physical and mental health.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

Estimating High-Order Functional Connectivity Networks for Mild Cognitive Impairment Identification Based on Topological Structure

Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse representation (SR), and Sparse low-rank representation have been proposed to estimate FCNs. Despite their popularity, they only capture the low-order connections of the brain regions, failing to encode more complex relationships (i.e. , high-order relationships). Although researchers have proposed high-order methods, like PC + PC and SR + SR, aiming to build FCNs that can reflect more real state of the brain. However, such methods only consider the relationships between brain regions during the FCN construction process, neglecting the potential shared topological structure information between FCNs of different subjects. In addition, the low-order relationships are always neglected during the construction of high-order FCNs. To address these issues, in this paper we proposed a novel method, namely Ho-FCNTops, towards estimating high-order FCNs based on brain topological structure. Specifically, inspired by the Group-constrained sparse representation (GSR), we first introduced a prior assumption that all subjects share the same topological structure in the construction of the low-order FCNs. Subsequently, we employed the Correlation-reserved embedding (COPE) to eliminate noise and redundancy from the low-order FCNs. Meanwhile, we retained the original low-order relationships during the embedding process to obtain new node representations. Finally, we utilized the SR method on the obtained new node representations to construct the Ho-FCNTops required for disease identification. To validate the effectiveness of the proposed method, experiments were conducted on 137 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to identify Mild Cognitive Impairment (MCI) patients from the normal controls. The experimental results demonstrate superior performance compared to baseline methods.

Newly self-administered two-step tool for screening cognitive function in an ageing Chinese population:an exploratory cross-sectional study

Background Early screening of cognitive function is critical to dementia treatment and care.However,traditional tests require face-to-face administration and are often limited by implementation costs and biases.Aims This study aimed to assess whether the Thoven Cognitive Self-Assessment(TCSA),a novel,innovative two-step touchscreen-based cognition assessment tool,could identify early cognitive impairment due to dementia in older adults.Methods The TCSA was administered to 61 healthy controls(HCs),46 participants with mild cognitive impairment(MCI)and 44 participants diagnosed with dementia recruited from Shanghai.Two outcome measures were generated from the TCSA test:the TCSA_(primary task)score and the TCSA_(secondary task)score.Results The total average scores in the control group for the TCSA_(primary task)and TCSA_(secondary task)were significantly higher than those in the MCI and dementia groups(TCSA_(primary task):HCs vs MCI group vs dementia group,8.58±1.76 vs 5.40±2.67 vs 2.74±2.11,F=75.40,p<0.001;TCSA_(secondary task):HCs vs MCI group vs dementia group,23.02±3.31 vs 17.95±4.93 vs 11.93±5.50,F=76.46,p<0.001).Moreover,receiver operating characteristic analysis showed that a score below 7.5 for the TCSA_(primary task)and a score below 22.5 for the TCSA_(secondary task)were indicators of MCI.Conclusions The TCSA appears to be efficacious for the detection of cognitive impairment in older adults.It demonstrates the potential for large-scale cognition screening in community service settings.

Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

Diabetes and cognitive function:An evidence-based current perspective

Several epidemiological studies have clearly identified diabetes mellitus(DM)as a major risk factor for cognitive dysfunction,and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world.Brain and neural tissues predominantly depend on glucose as energy substrate and hence,any alterations in carbohydrate metabolism can directly impact on cerebral functional output including cognition,executive capacity,and memory.DM affects neuronal function and mental capacity in several ways,some of which include hypoperfusion of the brain tissues from cerebrovascular disease,diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism,local hyper-and hypometabolism of brain areas from insulin resistance,and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage.Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients.Therefore,it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients.A thorough appraisal of normal metabolic characteristics of the brain,how alterations in neural metabolism affects cognition,the diagnostic algorithm for patients with diabetes and dementia,and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context.This evidence-based narrative with the backup of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.

Relationship between glycemic variability and cognitive function in lacune patients with type 2 diabetes

BACKGROUND Lacunes are the manifestations of lacunar infarction which can lead many patients to the clinical outcome of disability or dementia.However,the relationship between lacune burden,cognitive function and blood glucose fluctuation in patients with type 2 diabetes mellitus(T2DM)complicated with lacunes is not very clear.AIM To explore the correlation between glucose variability,lacune burden and cognitive function in patients with lacunes complicated with T2DM.METHODS The clinical and imaging data of 144 patients with lacunes combined with T2DM were reviewed retrospectively.72 h continuous glucose monitoring was performed.The Montreal Cognitive Assessment was used to assess cognitive function.The burden of lacunes was evaluated using magnetic resonance imaging performance.Multifactorial logistic regression analysis was used to study the affecting the lacune load and cognitive impairment in patients.To predict the value of patients’cognitive impairment with lacunes complicated with T2DM,a receiver operating characteristic(ROC)curve and a nomogram prediction model were constructed.RESULTS The standard deviation(SD)of the average blood glucose concentration,percentage coefficient of variation(%CV)and time of range(TIR)were significantly different between the low and the high load groups(P<0.05).The SD,%CV and TIR of the cognitive impairment group and non-cognitive impairment group were significantly different(P<0.05).SD(odds ratio(OR):3.558,95%confidence interval(CI):1.268-9.978,P=0.006),and%CV(OR:1.192,95%CI:1.081-1.315,P<0.05)were the risk factors for an increased infarct burden in lacunes patients complicated with T2DM.TIR(OR:0.874,95%CI:0.833-0.928,P<0.05)is a protective factor.In addition,an increased SD(OR:2.506,95%CI:1.008-6.23,P=0.003),%CV(OR:1.163,95%CI:1.065-1.270,P<0.05)were the risk factors for cognitive impairment in patients with lacunes complicated with T2DM,TIR(OR:0.957,95%CI:0.922-0.994,P<0.05)is a protective factor.A nomogram prediction model of the risk of cognitive impairment was established based on SD,%CV and TIR.Decision curve analysis and the internal calibration analysis were used for internal verification and showed that the model was clinical benefit.The area under the ROC curves for predicting cognitive impairment in patients with lacunes complicated with T2DM was drawn were%CV:0.757(95%CI:0.669-0.845,P<0.05),TIR:0.711(95%CI:0.623-0.799,P<0.05).CONCLUSION Blood glucose variability is closely associated with the level of lacune burden and cognitive dysfunction in lacune patients combined with T2DM.%CV,TIR have a certain predictive effect in cognitive impairment in lacune patients.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Association between vision and cognitive function among community-dwelling older adults in Selangor,Malaysia

AIM:To determine the association between distance and near visual acuity(VA)and cognitive function among older adults in Selangor,Malaysia.METHODS:A total of 230 older adults(age≥60y)participated in this study.Habitual distance and near VA were measured using the Early Treatment Diabetic Retinopathy Study Chart and Lighthouse Near Visual Acuity Chart,respectively.Global cognitive function was assessed using the Mini-Mental State Examination(M-MSE)and the Malay language version of the Montreal Cognitive Assessment(M-MoCA).Digit Symbol(DS)subtest was used to measure information processing.RESULTS:No significant association was observed between vision and M-MSE and M-MoCA scores.However,poor distance and near VA were found to be significantly associated with low DS scores[distance VA:β=-0.01,R2=0.1,P=0.02;odds ratio(OR)=2.84,95%confidence interval(CI),1.10-7.33,P=0.03;near VA:β=-0.05,R2=0.08,P=0.00;OR=3.32,95%CI,1.28-8.59,P=0.01].CONCLUSION:Poor vision is associated with a decline in information processing in older adults and substantiates the importance of preserving good vision in maintaining cognitive function.

Relationship between left-behind status and cognitive function in older Chinese adults: a prospective 3-year cohort study

Background Due to the inaccuracy of the traditional geographical distance-based definition of left-behind status,data on the negative effect of left-behind status on cognitive function among older adults are controversial.Aims This study examined the cross-sectional and longitudinal associations of left-behind status with cognitive function in older Chinese adults.The left-behind status definition was based on the frequency of face-to-face parent-child meetings.Methods Data from a nationally representative sample of 8682 older adults(60+years)in 2015(5658 left behind and 3024 non-left behind),of which 6933 completed the follow-up in 2018,were obtained from the China Health and Retirement Longitudinal Study.Left-behind older adults werebroadlydefined as those aged 60+years who had living adult children and saw their children less than once per month.The cognitive function was assessed with a composite cognitive test with higher total scores indicating better cognitive function.Results Left-behind older adults had significantly lower cognitive test scores than non-left-behind older adults in both 2015(11.1(6.0)vs 13.2(5.9),t=15.863,p<0.001)and 2018(10.0(6.6)vs 12.4(6.7),t=14.177,p<0.001).After adjusting for demographic factors,lifestyle factors,chronic medical conditions and the baseline cognitive test score(in the longitudinal analysis only),on average,the cognitive test score of left-behind older adults was 0.628 lower than their non-left-behind counterparts in 2015(t=5.689,p<0.001).This difference in cognitive test scores attenuated to 0.322 but remained significant in 2018(t=2.733,p=0.006).Conclusions Left-behind older Chinese adults have a higher risk of poor cognitive function and cognitive decline than their non-left-behind counterparts.Specific efforts targeting left-behind older adults,such as encouraging adult children to visit their parents more regularly,are warranted to maintain or delay the progression of cognitive decline.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.