Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that c...Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.展开更多
Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship betwee...Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.展开更多
BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To i...BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.展开更多
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 repre...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-FCN<sub>Tops</sub>, 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-FCN<sub>Tops</sub> 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.展开更多
β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to...β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.展开更多
Mild cognitive impairment(MCI)is a prodrome of Alzheimer’s disease pathology.Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods.Exosome...Mild cognitive impairment(MCI)is a prodrome of Alzheimer’s disease pathology.Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods.Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases.This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI.Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls,and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays.Correlation of cognitive performance with the serum exosomal protein level was determined.Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls.We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis.Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients.Exosomal fibulin-1,with an area under the curve value of 0.81,may be a biomarker for an MCI diagnosis.The exosomal protein signature from MCI patients reflected the cell adhesion molecule category.In particular,higher exosomal fibulin-1 levels correlated with lower cognitive performance.Thus,this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI.展开更多
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...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.展开更多
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Sin...Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.展开更多
Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-indu...Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has been extensively shown to cause many neurological sequelae,and cognitive deficits(known as“brain fog”)may particularly and widely occur even in...Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has been extensively shown to cause many neurological sequelae,and cognitive deficits(known as“brain fog”)may particularly and widely occur even in individuals with mild symptoms[1].Peripheral hyperinflammation as well as central nervous system(CNS)local immune responses may synergistically contribute to brain autoimmune injury.In addition to the direct neuroinvasion of SARS-CoV-2 and nonimmune effects such as severe systemic hypoxemia and vascular thrombosis,the central mechanism by which SARSCoV-2 accelerates cognitive-related symptoms may be related to immune effects[2].However,the precise neuroinflammatory mechanisms of SARS-CoV-2 infection have not been fully established.Fernández-Casta-da et al.[3]provided direct evidence and unique insights into the potential mechanism of cognitive impairment in mild respiratory coronavirus disease 2019(COVID-19)cases.展开更多
The structure and function of brain networks have been altered in patients with end-stage renal disease(ESRD).Manifold regularization(MR)only considers the pairing relationship between two brain regions and cannot rep...The structure and function of brain networks have been altered in patients with end-stage renal disease(ESRD).Manifold regularization(MR)only considers the pairing relationship between two brain regions and cannot represent functional interactions or higher-order relationships between multiple brain regions.To solve this issue,we developed a method to construct a dynamic brain functional network(DBFN)based on dynamic hypergraph MR(DHMR)and applied it to the classification of ESRD associated with mild cognitive impairment(ESRDaMCI).The construction of DBFN with Pearson’s correlation(PC)was transformed into an optimization model.Node convolution and hyperedge convolution superposition were adopted to dynamically modify the hypergraph structure,and then got the dynamic hypergraph to form the manifold regular terms of the dynamic hypergraph.The DHMR and L_(1) norm regularization were introduced into the PC-based optimization model to obtain the final DHMR-based DBFN(DDBFN).Experiment results demonstrated the validity of the DDBFN method by comparing the classification results with several related brain functional network construction methods.Our work not only improves better classification performance but also reveals the discriminative regions of ESRDaMCI,providing a reference for clinical research and auxiliary diagnosis of concomitant cognitive impairments.展开更多
Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by ...Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.展开更多
AIM:To investigate the relationship between near point of convergence(NPC)and mild cognitive impairment(MCI)in the general elderly population.METHODS:The present report is a part of the Tehran Geriatric Eye Study(TGES...AIM:To investigate the relationship between near point of convergence(NPC)and mild cognitive impairment(MCI)in the general elderly population.METHODS:The present report is a part of the Tehran Geriatric Eye Study(TGES):a population-based crosssectional study conducted on individuals 60 years of age and above living in Tehran,Iran using the multi-stage stratified random cluster sampling method.Cognitive status was assessed using the Persian version of the Mini-Mental State Examination(MMSE).All study participants underwent complete ocular examination including measurement of uncorrected and best-corrected visual acuity,objective and subjective refraction,cover testing,NPC measurement,and slit-lamp biomicroscopy.RESULTS:The data of 1190 individuals were analyzed for this report.The mean age of the participants analyzed was 66.82±5.42(60-92y)and 728(61.2%)of them were female.Patients with MCI had a significantly more receded NPC compared to subjects with normal cognitive status(10.89±3.58 vs 7.76±2.71 cm,P<0.001).In the multivariable logistic regression model and in the presence of confounding variables,a receded NPC was statistically significantly associated with an increased risk of MCI(odds ratio:1.334,95%confidence interval:1.263 to 1.410,P<0.001).According to receiver operating characteristic(ROC)analysis,a cut point NPC>8.5 cm(area under the curve:0.764,P<0.001)could predict the presence of MCI with a sensitivity and specificity of 70.9%and 69.5%,respectively.CONCLUSION:A receded NPC can be clinically proposed as a predictor of MCI in older adults.It is recommended that elderly with a receded NPC>8.50 cm undergo detailed cognitive screening for a definite diagnosis of MCI.In this case,the necessary interventions can be carried out to slow down MCI progression to dementia.展开更多
Dementia prevalence has soared due to population aging. In Mild Cognitive Impairment (MCI) as a pre-dementia stage, sleepdisturbances have raised much interest as a factor in a bidirectional relationship with cognitiv...Dementia prevalence has soared due to population aging. In Mild Cognitive Impairment (MCI) as a pre-dementia stage, sleepdisturbances have raised much interest as a factor in a bidirectional relationship with cognitive decline. Thus, this studydeveloped the Sleep and Cognition Enhancement Multimodal Intervention (SCEMI) based on Lazarus’ multimodal approachand conducted a randomized controlled experiment to investigate the effects of the novel program on sleep and cognition inMCI elderly. The participants were 55 MCI elderly with sleep disturbances at two dementia care centers located in S-city,Gyeonggi-do, South Korea (n = 25 in the experimental group and n = 30 in the control group). The study period was fromNovember 01 to December 27, 2022. The experimental group received 8 sessions of SCEMI, 60 min per session once a week.The control group received general education and guidance using a simplified booklet on the sleep and cognitive improvement.For data collection, a self-reported questionnaire was used to investigate sleep quality, presleep arousal, cognitive function,stress, and depression. The results showed that, compared to the control group, the experimental group had significantlyimproved across all variables: sleep quality (U = 109.50, p < 0.001), presleep arousal (U = 11.50, p < 0.001), cognitive function(U = 72.00, p < 0.001), stress (U = 139.00, p < 0.001), and depression (U = 231.50, p = 0.015). Thus, the SCEMI appears topositively affect symptomatic improvement and delays the progression to dementia as an integrated intervention to enhancesleep and cognition in community-dwelling MCI elderly with sleep disturbances.展开更多
Objective:To observe the effect of electroacupuncture(EA)at"Baihui"(GV20)and"Shenshu"(BL23)on cognitive impairment in AD model mice,and to explore its mechanism.Methods:A total of 24 model mice wer...Objective:To observe the effect of electroacupuncture(EA)at"Baihui"(GV20)and"Shenshu"(BL23)on cognitive impairment in AD model mice,and to explore its mechanism.Methods:A total of 24 model mice were randomly divided into EA,medication and model groups,8 mice in each group.Another 8 C57BL/6J mice were used as the normal control.The rats in the EA group were treated with electrical stimulation at Baihui(GV20)and Shenshu(BL23),and those in the medication group were treated with donepezil hydrochloride,once a day for 21 days.Adopting the Maorris water maze method to detect the behavior of mice and using HE staining to observe the morphological structure of neurons in the hippocampal region of mice.Finally the expression of GSK-3βandβ-catenin protein contents in the hippocampus of mice in each group was detected by Western blot.Results:Compared to the model group,the evasion latency of the electroacupuncture group and the western medicine group were significantly shorter,and the dwell time in the target quadrant and the number of crossing the plateau were increased(P<0.05),and the hippocampal neurons in each treatment group were closely arranged and complete,with a clearer hierarchy.Western blot assay results showed that the expression ofβ-catenin protein was significantly increased and GSK-3βprotein expression was decreased in the hippocampal region of mice in the electroacupuncture and western medicine groups compared with the model group(P<0.05).Conclusion:Ea at"Baihui"(GV20)and"Shenshu"(BL23)can significantly improve the cognitive function of APP/PS1 mice,which may be connected with the activation of Wnt/β-catenin signaling pathway.展开更多
BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which ...BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.展开更多
BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects o...BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.展开更多
During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to me...During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82274611 (to LZ),82104419 (to DM)Capital Science and Technology Leading Talent Training Project,No.Z1 91100006119017 (to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803 (to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006 (to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017 (to DM)Beijing Gold-Bridge Project,No.ZZ20145 (to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
基金supported by MH101874 (to CFZ)MH122379 (to CFZ)the Taylor Family Institute for Innovative Psychiatric Research and the Bantly Foundation (to CFZ)。
文摘Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.
基金supported by National Natural Science Foundation of China(No.82001239)Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support,code(NO.202112)。
文摘Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.
文摘BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.
文摘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-FCN<sub>Tops</sub>, 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-FCN<sub>Tops</sub> 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.
基金supported by the National Natural Science Foundation of China,No.81771337(to RQY).
文摘β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.
基金supported by the National Natural Science Foundation of China,No.81801071(to YJL)Top-notch Postgraduate Talent Cultivation Program of Chongqing Medical University,No.BJRC202106(to BC).
文摘Mild cognitive impairment(MCI)is a prodrome of Alzheimer’s disease pathology.Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods.Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases.This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI.Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls,and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays.Correlation of cognitive performance with the serum exosomal protein level was determined.Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls.We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis.Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients.Exosomal fibulin-1,with an area under the curve value of 0.81,may be a biomarker for an MCI diagnosis.The exosomal protein signature from MCI patients reflected the cell adhesion molecule category.In particular,higher exosomal fibulin-1 levels correlated with lower cognitive performance.Thus,this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI.
基金National Natural Science Foundation of China,Nos.81771160 (to ZZ),81671060 (to CC),31970973 (to JW),21921004 (to FX)Translational Medicine and In terdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,No.ZNJC201934 (to ZZ)。
文摘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.
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
文摘Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.
基金the Youth Fund of the Shanghai Municipal Health Commission(No.20164Y0266).
文摘Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.
基金supported by grants from the National Natural Science Foundation of China(82001240)Natural Science Foundation of Heilongjiang Province(YQ2021H011)+1 种基金China Postdoctoral Science Foundation(2020M670925,2022T150172)Postdoctoral Foundation of Heilongjiang Province(LBHZ19027,LBH-TZ2019).
文摘Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has been extensively shown to cause many neurological sequelae,and cognitive deficits(known as“brain fog”)may particularly and widely occur even in individuals with mild symptoms[1].Peripheral hyperinflammation as well as central nervous system(CNS)local immune responses may synergistically contribute to brain autoimmune injury.In addition to the direct neuroinvasion of SARS-CoV-2 and nonimmune effects such as severe systemic hypoxemia and vascular thrombosis,the central mechanism by which SARSCoV-2 accelerates cognitive-related symptoms may be related to immune effects[2].However,the precise neuroinflammatory mechanisms of SARS-CoV-2 infection have not been fully established.Fernández-Casta-da et al.[3]provided direct evidence and unique insights into the potential mechanism of cognitive impairment in mild respiratory coronavirus disease 2019(COVID-19)cases.
基金supported by the National Natural Science Foundation of China (No.51877013),(ZJ),(http://www.nsfc.gov.cn/)the Jiangsu Provincial Key Research and Development Program (No.BE2021636),(ZJ),(http://kxjst.jiangsu.gov.cn/)+1 种基金the Science and Technology Project of Changzhou City (No.CE20205056),(ZJ),(http://kjj.changzhou.gov.cn/)by Qing Lan Project of Jiangsu Province (no specific grant number),(ZJ),(http://jyt.jiangsu.gov.cn/).
文摘The structure and function of brain networks have been altered in patients with end-stage renal disease(ESRD).Manifold regularization(MR)only considers the pairing relationship between two brain regions and cannot represent functional interactions or higher-order relationships between multiple brain regions.To solve this issue,we developed a method to construct a dynamic brain functional network(DBFN)based on dynamic hypergraph MR(DHMR)and applied it to the classification of ESRD associated with mild cognitive impairment(ESRDaMCI).The construction of DBFN with Pearson’s correlation(PC)was transformed into an optimization model.Node convolution and hyperedge convolution superposition were adopted to dynamically modify the hypergraph structure,and then got the dynamic hypergraph to form the manifold regular terms of the dynamic hypergraph.The DHMR and L_(1) norm regularization were introduced into the PC-based optimization model to obtain the final DHMR-based DBFN(DDBFN).Experiment results demonstrated the validity of the DDBFN method by comparing the classification results with several related brain functional network construction methods.Our work not only improves better classification performance but also reveals the discriminative regions of ESRDaMCI,providing a reference for clinical research and auxiliary diagnosis of concomitant cognitive impairments.
基金supported in part by grants from National Natural Science Foundation of China(No.31929002,No.82201326 No.82071440 and No.92049107)Science,Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20210324141405014)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020B1515120017)the Academic Frontier Youth Team Project to Xiao-chuan WANG from Huazhong University of Science and Technology.
文摘Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.
基金Supported by Iran University of Medical Sciences (IUMS)。
文摘AIM:To investigate the relationship between near point of convergence(NPC)and mild cognitive impairment(MCI)in the general elderly population.METHODS:The present report is a part of the Tehran Geriatric Eye Study(TGES):a population-based crosssectional study conducted on individuals 60 years of age and above living in Tehran,Iran using the multi-stage stratified random cluster sampling method.Cognitive status was assessed using the Persian version of the Mini-Mental State Examination(MMSE).All study participants underwent complete ocular examination including measurement of uncorrected and best-corrected visual acuity,objective and subjective refraction,cover testing,NPC measurement,and slit-lamp biomicroscopy.RESULTS:The data of 1190 individuals were analyzed for this report.The mean age of the participants analyzed was 66.82±5.42(60-92y)and 728(61.2%)of them were female.Patients with MCI had a significantly more receded NPC compared to subjects with normal cognitive status(10.89±3.58 vs 7.76±2.71 cm,P<0.001).In the multivariable logistic regression model and in the presence of confounding variables,a receded NPC was statistically significantly associated with an increased risk of MCI(odds ratio:1.334,95%confidence interval:1.263 to 1.410,P<0.001).According to receiver operating characteristic(ROC)analysis,a cut point NPC>8.5 cm(area under the curve:0.764,P<0.001)could predict the presence of MCI with a sensitivity and specificity of 70.9%and 69.5%,respectively.CONCLUSION:A receded NPC can be clinically proposed as a predictor of MCI in older adults.It is recommended that elderly with a receded NPC>8.50 cm undergo detailed cognitive screening for a definite diagnosis of MCI.In this case,the necessary interventions can be carried out to slow down MCI progression to dementia.
文摘Dementia prevalence has soared due to population aging. In Mild Cognitive Impairment (MCI) as a pre-dementia stage, sleepdisturbances have raised much interest as a factor in a bidirectional relationship with cognitive decline. Thus, this studydeveloped the Sleep and Cognition Enhancement Multimodal Intervention (SCEMI) based on Lazarus’ multimodal approachand conducted a randomized controlled experiment to investigate the effects of the novel program on sleep and cognition inMCI elderly. The participants were 55 MCI elderly with sleep disturbances at two dementia care centers located in S-city,Gyeonggi-do, South Korea (n = 25 in the experimental group and n = 30 in the control group). The study period was fromNovember 01 to December 27, 2022. The experimental group received 8 sessions of SCEMI, 60 min per session once a week.The control group received general education and guidance using a simplified booklet on the sleep and cognitive improvement.For data collection, a self-reported questionnaire was used to investigate sleep quality, presleep arousal, cognitive function,stress, and depression. The results showed that, compared to the control group, the experimental group had significantlyimproved across all variables: sleep quality (U = 109.50, p < 0.001), presleep arousal (U = 11.50, p < 0.001), cognitive function(U = 72.00, p < 0.001), stress (U = 139.00, p < 0.001), and depression (U = 231.50, p = 0.015). Thus, the SCEMI appears topositively affect symptomatic improvement and delays the progression to dementia as an integrated intervention to enhancesleep and cognition in community-dwelling MCI elderly with sleep disturbances.
基金Postgraduate Program of the Third Affiliated Hospital of Beijing University of Chinese Medicine(2019-XS-ZB13)。
文摘Objective:To observe the effect of electroacupuncture(EA)at"Baihui"(GV20)and"Shenshu"(BL23)on cognitive impairment in AD model mice,and to explore its mechanism.Methods:A total of 24 model mice were randomly divided into EA,medication and model groups,8 mice in each group.Another 8 C57BL/6J mice were used as the normal control.The rats in the EA group were treated with electrical stimulation at Baihui(GV20)and Shenshu(BL23),and those in the medication group were treated with donepezil hydrochloride,once a day for 21 days.Adopting the Maorris water maze method to detect the behavior of mice and using HE staining to observe the morphological structure of neurons in the hippocampal region of mice.Finally the expression of GSK-3βandβ-catenin protein contents in the hippocampus of mice in each group was detected by Western blot.Results:Compared to the model group,the evasion latency of the electroacupuncture group and the western medicine group were significantly shorter,and the dwell time in the target quadrant and the number of crossing the plateau were increased(P<0.05),and the hippocampal neurons in each treatment group were closely arranged and complete,with a clearer hierarchy.Western blot assay results showed that the expression ofβ-catenin protein was significantly increased and GSK-3βprotein expression was decreased in the hippocampal region of mice in the electroacupuncture and western medicine groups compared with the model group(P<0.05).Conclusion:Ea at"Baihui"(GV20)and"Shenshu"(BL23)can significantly improve the cognitive function of APP/PS1 mice,which may be connected with the activation of Wnt/β-catenin signaling pathway.
基金The study was reviewed and approved by the Institutional Review Board of Chaohu Hospital Affiliated to AnhuiMedical University,Approval No.KYXM-202208-011.
文摘BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.
基金This study was approved by the Ethics Committee of Shengjing Hospital of China Medical University.
文摘BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.
文摘During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.
