Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregati...Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.展开更多
Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to...Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.展开更多
BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patie...BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.展开更多
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
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
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
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
Background:Over 55 million people worldwide are living with dementia.The rate of cognitive decline increases with age,and loss of senses may be a contributing factor.Objectives:This study aimed to analyze hearing,olfa...Background:Over 55 million people worldwide are living with dementia.The rate of cognitive decline increases with age,and loss of senses may be a contributing factor.Objectives:This study aimed to analyze hearing,olfactory function,and color vision in patients with dementia.Materials and methods:The sample comprised 40 patients with dementia and 37 cognitively normal controls aged 41–85 years.All participants underwent conventional pure-tone audiometry and a screening version of the Hearing Handicap Inventory for Adults,the Odorized Markers Test of olfactory function and the Ishihara color vision test.The effects of comorbidities and lifestyle factors were also assessed.Results:Patients with dementia had significantly worse hearing at almost all frequencies tested and significantly greater olfactory impairment than cognitively normal controls.Color vision impairment was found in less than 8%of the sample,with no significant difference between the groups.Impairment of two senses(hearing and olfaction)was significantly more common in patients with dementia than in controls.Conclusion:Individuals with dementia were found to have sensory decline,namely hearing and olfactory impairment.Color vision was rarely impaired in the sample.Participants with dementia tended to have more multisensory impairments than controls.展开更多
Objective:Cancer survivors have experienced subjective cognitive impairment(SCI)when they received cancer diagnoses or treatments.Their psychosocial and emotional statuses were also impacted.With the advancement of we...Objective:Cancer survivors have experienced subjective cognitive impairment(SCI)when they received cancer diagnoses or treatments.Their psychosocial and emotional statuses were also impacted.With the advancement of web technologies,web-based cognitive interventions have been implemented in the management and the alleviation of the SCI,the psychosocial distress,and the emotional distress in cancer survivors.This review aimed to summarize the intervention contents of web-based cognitive interventions for SCI,and to explore the effects of the interventions on SCI,psychosocial status,and emotional health.Methods:Six databases(CINAHL Plus,Cochrane Library,Embase,APA PsycInfo,PubMed and CNKI)were searched from the establishment of databases up to December 2023.Literature references were also manually searched for related articles.Results:This review contained 21 studies that covered the contents of web-based cognitive interventions,such as computer-assisted cognitive training,online cognitive rehabilitation,cognitive behavior therapy with the Internet,telehealth physical exercise,and web-based mindfulness interventions.The effects of web-based cognitive interventions positively impacted SCI for cancer survivors.Also,these interventions showed varying degrees of effectiveness in alleviating psychosocial and emotional distresses.Conclusion:By summarizingfive types of cognitive intervention contents delivered via web technology,this review demonstrated that web-based cognitive interventions optimized SCI and overall psychosocial and emotional statuses for the cancer survivors.It is recommended that future research focus on the development of customized web-based cognitive interventions for individuals with SCI,along with their psychosocial and emotional statuses.展开更多
Neurosyphilis(NS)is an infectious disease caused by Treponema pallidum invading the central nervous system.It can manifest at any stage of syphilis,and is often misdiagnosed due to its atypical and progressive symptom...Neurosyphilis(NS)is an infectious disease caused by Treponema pallidum invading the central nervous system.It can manifest at any stage of syphilis,and is often misdiagnosed due to its atypical and progressive symptoms.The increasing incidence of NS underscores the necessity for early and accurate diagnosis.Here,we present a case where routine cerebrospinal fluid metagenomic next-generation sequencing(mNGS)was used to diagnose a patient with neurosyphilis.The patient exhibited cognitive impairment and was initially diagnosed with cerebral infarction due to syphilitic cerebral arteritis.Thus,the patient was treated with dual antiplatelet therapy(aspirin and clopidogrel)and statins to stabilize the plaques.Neurosyphilis was treated with penicillin sodium injections,resulting in significant improvement in the patient’s mental state.This case is a rare instance of neurosyphilis associated with cerebral infarction.These findings suggest that mNGS is a valuable tool in diagnosing neurosyphilis,potentially improving diagnostic accuracy and patient outcomes.展开更多
Neuroimaging has emerged over the last few decades as a crucial tool in diagnosing Alzheimer’s disease(AD).Mild cognitive impairment(MCI)is a condition that falls between the spectrum of normal cognitive function and...Neuroimaging has emerged over the last few decades as a crucial tool in diagnosing Alzheimer’s disease(AD).Mild cognitive impairment(MCI)is a condition that falls between the spectrum of normal cognitive function and AD.However,previous studies have mainly used handcrafted features to classify MCI,AD,and normal control(NC)individuals.This paper focuses on using gray matter(GM)scans obtained through magnetic resonance imaging(MRI)for the diagnosis of individuals with MCI,AD,and NC.To improve classification performance,we developed two transfer learning strategies with data augmentation(i.e.,shear range,rotation,zoom range,channel shift).The first approach is a deep Siamese network(DSN),and the second approach involves using a cross-domain strategy with customized VGG-16.We performed experiments on the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset to evaluate the performance of our proposed models.Our experimental results demonstrate superior performance in classifying the three binary classification tasks:NC vs.AD,NC vs.MCI,and MCI vs.AD.Specifically,we achieved a classification accuracy of 97.68%,94.25%,and 92.18%for the three cases,respectively.Our study proposes two transfer learning strategies with data augmentation to accurately diagnose MCI,AD,and normal control individuals using GM scans.Our findings provide promising results for future research and clinical applications in the early detection and diagnosis of AD.展开更多
SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study...SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.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 The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main m...BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.展开更多
Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on id...Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on identifying its active ingredients and their target proteins.Methods:The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe.It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database.These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe’s core active ingredients.In vitro cell experiments were conducted on hypoxic HT22 cells,involving CCK8 assay,lentiviral transfection to silence autophagy related 9B(ATG9B),immunofluorescence staining,and qPCR validation to investigate the effects of the recipe on autophagy.Results:The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network.Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs.Molecular docking showed quercetin,kaempferol,myrcene,and conferone as key ingredients targeting autophagy-related proteins.Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions,reduced apoptosis,and modulated the expression of autophagy-related factors,thereby decreasing apoptosis rates in HT22 cells.Conclusion:The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins.Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions,though further research is needed to fully understand its mechanisms and clinical applications.展开更多
BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently ...BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently leads to neuropsychiatric co-mplications,such as cognitive impairment,anxiety,and depressive symptoms,which adversely affect patients’quality of life and rehabilitation.Neutrophil ge-latinase-associated lipocalin(NGAL)has emerged as a potential biomarker for various conditions,including AIS.This study investigated the association bet-ween serum NGAL levels at admission and neuropsychiatric complications in patients with AIS.neuropsychiatric complications in patients with AIS.METHODS Between January 2022 and December 2023,150 patients with AIS were enrolled.Serum NGAL levels were measured at admission using an enzyme-linked immu-nosorbent assay.Cognitive function was assessed using the Mini-Mental State Examination,while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge.The relationship between serum NGAL levels and cognitive impairment,anxiety,and depressive symptoms was analyzed using multivariate logistic regression,adjusted for potential con-founders of age,sex,body mass index,smoking status,hypertension,diabetes mellitus,dyslipidemia,previous stroke,and stroke severity.RESULTS The mean age of the participants was 65.4±10.2 years,and 58%were males.Prevalence rates of cognitive impairment,anxiety,and depressive symptoms at discharge were 34.7%,28.0%,and 32.0%,respectively.Serum NGAL levels were significantly higher in patients with cognitive impairment(median:5.6 ng/mL vs 3.2 ng/mL,P<0.001),anxiety(median:5.1 ng/mL vs 3.5 ng/mL,P=0.002),and depressive symptoms(median:5.4 ng/mL vs 3.3 ng/mL,P<0.001),compared to those without these conditions.Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment[odds ratio(OR)=1.42,95%confidence interval(CI):1.18-1.71,P<0.001],anxiety(OR=1.28,95%CI:1.09-1.51,P=0.003),and depressive symptoms(OR=1.39,95%CI:1.16-1.67,P<0.001)after adjusting for potential confounders.CONCLUSION Elevated serum NGAL levels were independently associated with cognitive impairment,anxiety,and depressive symptoms in patients with AIS;and may function as potential biomarkers for patients at risk.展开更多
BACKGROUND Mild cognitive impairment(MCI)in elderly individuals is a transitional stage between normal cognition and dementia.Understanding the risk factors for MCI and identifying those at high risk are extremely imp...BACKGROUND Mild cognitive impairment(MCI)in elderly individuals is a transitional stage between normal cognition and dementia.Understanding the risk factors for MCI and identifying those at high risk are extremely important for the elderly population.AIM To analyze the risk factors for MCI in the elderly population and construct a clinical prediction model.METHODS Total 295 elderly individuals presenting with memory loss diagnosed at Wuxi People's Hospital between March 2021 and March 2024 were included.Comprehensive demographic,clinical,and serological data were collected for analysis.Participants were categorized into either an MCI group or a normal group based on their performance on the Montreal Cognitive Assessment Scale.An elaborate clinical predictive model was developed to predict the likelihood of MCI in stroke patients;its accuracy was evaluated using area under curve values and calibration curves.RESULTS The results of the study showed that old age,hypertension,diabetes,hyperlipidemia,smoking,high-salt diet,high-cholesterol diet,decreased red blood count,increased neutrophil lymphocyte ratio and increased low-density lipoprotein cholesterol were risk factors for the onset of MCI,with A high vitamin diet and elevated high-density lipoprotein cholesterol being protective factors.In addition,the prediction model constructed in this study exhibits good degrees of differentiation and calibration.CONCLUSION The risk factors for MCI are diverse.Early identification of individuals at high risk of MCI can better intervene and improve their quality of life of MCI patients.展开更多
BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder(MDD).Understanding their relationships is crucial for developing targeted interventio...BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder(MDD).Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients.We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments.We also hypothesize that anxiety symptoms,especially psychic anxiety,is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors.AIM To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode.METHODS A comprehensive neurocognitive test battery assessed executive function,attention,processing speed,and memory in 162 medication-free MDD patients and 142 matched healthy controls.The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms,and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms.Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms,as well as their interactions,on cognitive impairments.RESULTS Among the depressive symptoms,sleep disturbances were associated with poorer executive function(P=0.004),lower processing speed(P=0.047),and memory impairments(P<0.001),and psychomotor retardation(PR)was associated with lower processing speed in patients with MDD(P=0.019).Notably,PR was found to mediate the impact of sleep disturbances on the processing speed.Regarding anxiety symptoms,psychic anxiety,rather than somatic anxiety,was associated with cognitive impairments in all aspects.Sleep disturbances mediated the effect of psychic anxiety on executive function[β=-0.013,BC CI(-0.027,-0.001)]and memory[β=-0.149,BC CI(-0.237,-0.063)],while PR mediated its effect on processing speed(β=-0.023,BC CI(-0.045,-0.004)].CONCLUSION Sleep disturbances may be a key predictor of poorer executive function,lower processing speed,and memory loss,while PR is crucial for lower processing speed during a depressive episode.Psychic anxiety contributes to all aspects of cognitive impairments,mediated by sleep disturbances and PR.展开更多
BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and...BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.展开更多
BACKGROUND Cognitive impairment,which manifests as a limited deterioration of specific functions associated with a particular disease,can lead to a general deterioration of the patient’s standard of living.Transcrani...BACKGROUND Cognitive impairment,which manifests as a limited deterioration of specific functions associated with a particular disease,can lead to a general deterioration of the patient’s standard of living.Transcranial magnetic stimulation,a noninvasive neuromodulation technique,is frequently employed to treat cognitive impairment in neuropsychiatric disorders.AIM To analyzed the state of international research on neuromodulation methods for treating cognitive impairment between 2014 and 2023,with the aim of exploring the state of research worldwide and the most recent developments in this particular area.METHODS Articles and reviews pertaining to neuromodulation methods for cognitive impairment were examined using the web of science database between January 2014 and December 2023.Publications,nations,organizations,writers,journals,citations,and keywords data from the identified studies were systematically analyzed using the CiteSpace 6.3.R1 software.RESULTS A total of 2371 documents with 11750 authors and 9461 institutions,with some cooccurrences,were retrieved.The quantity of yearly publications is showing an increasing trend.The United States and China have emerged as important contributors.Among the institutes,Harvard University had the highest number of publications,while Rossi S an author who is frequently cited.Initially,the primary keywords included human motor cortex,placebo-controlled trials,and serotonin reuptake inhibitors.However,the emphasis gradually moved to substance use disorders,supplementary motor areas,neural mechanisms,and exercise.CONCLUSION The use of neuromodulation techniques to treat cognitive impairment has drawn interest from academics all around the world.This study revealed hotspots and new trends in the research of transcranial magnetic stimulation as a cognitive impairment rehabilitation treatment.These findings are hold significant potential to guide further research and thus promote transcranial magnetic stimulation as a treatment method for cognitive impairment.展开更多
基金supported by the Research Foundation for Talented Scholars of Fujian Medical University,No.XRCZX2018014(to DZ)Startup Fund for Scientific Research,Fujian Medical University,No.2019QH1017(to CW)the Natural Science Foundation of Fujian Province,China,Nos.2021J01693(to DZ),2021J02032(to ZCY)。
文摘Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.
基金supported by the Scientific Research Project of China Rehabilitation Research Center,No.2021zx-23the National Natural Science Foundation of China,No.32100925the Beijing Nova Program,No.Z211100002121038。
文摘Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.
文摘BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.
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.
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.
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.
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 Czech Ministry of Health project NU20-09-00119.
文摘Background:Over 55 million people worldwide are living with dementia.The rate of cognitive decline increases with age,and loss of senses may be a contributing factor.Objectives:This study aimed to analyze hearing,olfactory function,and color vision in patients with dementia.Materials and methods:The sample comprised 40 patients with dementia and 37 cognitively normal controls aged 41–85 years.All participants underwent conventional pure-tone audiometry and a screening version of the Hearing Handicap Inventory for Adults,the Odorized Markers Test of olfactory function and the Ishihara color vision test.The effects of comorbidities and lifestyle factors were also assessed.Results:Patients with dementia had significantly worse hearing at almost all frequencies tested and significantly greater olfactory impairment than cognitively normal controls.Color vision impairment was found in less than 8%of the sample,with no significant difference between the groups.Impairment of two senses(hearing and olfaction)was significantly more common in patients with dementia than in controls.Conclusion:Individuals with dementia were found to have sensory decline,namely hearing and olfactory impairment.Color vision was rarely impaired in the sample.Participants with dementia tended to have more multisensory impairments than controls.
基金The National Natural Science Foundation of China supports this review(No.82172844)The funder had no role in study design,data collection and analysis,manuscript preparation,or decision to publish.
文摘Objective:Cancer survivors have experienced subjective cognitive impairment(SCI)when they received cancer diagnoses or treatments.Their psychosocial and emotional statuses were also impacted.With the advancement of web technologies,web-based cognitive interventions have been implemented in the management and the alleviation of the SCI,the psychosocial distress,and the emotional distress in cancer survivors.This review aimed to summarize the intervention contents of web-based cognitive interventions for SCI,and to explore the effects of the interventions on SCI,psychosocial status,and emotional health.Methods:Six databases(CINAHL Plus,Cochrane Library,Embase,APA PsycInfo,PubMed and CNKI)were searched from the establishment of databases up to December 2023.Literature references were also manually searched for related articles.Results:This review contained 21 studies that covered the contents of web-based cognitive interventions,such as computer-assisted cognitive training,online cognitive rehabilitation,cognitive behavior therapy with the Internet,telehealth physical exercise,and web-based mindfulness interventions.The effects of web-based cognitive interventions positively impacted SCI for cancer survivors.Also,these interventions showed varying degrees of effectiveness in alleviating psychosocial and emotional distresses.Conclusion:By summarizingfive types of cognitive intervention contents delivered via web technology,this review demonstrated that web-based cognitive interventions optimized SCI and overall psychosocial and emotional statuses for the cancer survivors.It is recommended that future research focus on the development of customized web-based cognitive interventions for individuals with SCI,along with their psychosocial and emotional statuses.
文摘Neurosyphilis(NS)is an infectious disease caused by Treponema pallidum invading the central nervous system.It can manifest at any stage of syphilis,and is often misdiagnosed due to its atypical and progressive symptoms.The increasing incidence of NS underscores the necessity for early and accurate diagnosis.Here,we present a case where routine cerebrospinal fluid metagenomic next-generation sequencing(mNGS)was used to diagnose a patient with neurosyphilis.The patient exhibited cognitive impairment and was initially diagnosed with cerebral infarction due to syphilitic cerebral arteritis.Thus,the patient was treated with dual antiplatelet therapy(aspirin and clopidogrel)and statins to stabilize the plaques.Neurosyphilis was treated with penicillin sodium injections,resulting in significant improvement in the patient’s mental state.This case is a rare instance of neurosyphilis associated with cerebral infarction.These findings suggest that mNGS is a valuable tool in diagnosing neurosyphilis,potentially improving diagnostic accuracy and patient outcomes.
基金Research work funded by Zhejiang Normal University Research Fund YS304023947 and YS304023948.
文摘Neuroimaging has emerged over the last few decades as a crucial tool in diagnosing Alzheimer’s disease(AD).Mild cognitive impairment(MCI)is a condition that falls between the spectrum of normal cognitive function and AD.However,previous studies have mainly used handcrafted features to classify MCI,AD,and normal control(NC)individuals.This paper focuses on using gray matter(GM)scans obtained through magnetic resonance imaging(MRI)for the diagnosis of individuals with MCI,AD,and NC.To improve classification performance,we developed two transfer learning strategies with data augmentation(i.e.,shear range,rotation,zoom range,channel shift).The first approach is a deep Siamese network(DSN),and the second approach involves using a cross-domain strategy with customized VGG-16.We performed experiments on the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset to evaluate the performance of our proposed models.Our experimental results demonstrate superior performance in classifying the three binary classification tasks:NC vs.AD,NC vs.MCI,and MCI vs.AD.Specifically,we achieved a classification accuracy of 97.68%,94.25%,and 92.18%for the three cases,respectively.Our study proposes two transfer learning strategies with data augmentation to accurately diagnose MCI,AD,and normal control individuals using GM scans.Our findings provide promising results for future research and clinical applications in the early detection and diagnosis of AD.
基金National Natural Science Foundation of China(82230043,82293642)。
文摘SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.
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.
基金Supported by National Natural Science Foundation of China,No.82270845。
文摘BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
文摘Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on identifying its active ingredients and their target proteins.Methods:The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe.It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database.These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe’s core active ingredients.In vitro cell experiments were conducted on hypoxic HT22 cells,involving CCK8 assay,lentiviral transfection to silence autophagy related 9B(ATG9B),immunofluorescence staining,and qPCR validation to investigate the effects of the recipe on autophagy.Results:The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network.Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs.Molecular docking showed quercetin,kaempferol,myrcene,and conferone as key ingredients targeting autophagy-related proteins.Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions,reduced apoptosis,and modulated the expression of autophagy-related factors,thereby decreasing apoptosis rates in HT22 cells.Conclusion:The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins.Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions,though further research is needed to fully understand its mechanisms and clinical applications.
基金Supported by Gansu Provincial Natural Science Foundation,No.20JR10RA671and The Fund of the First Hospital of Lanzhou University,No.ldyyyn2021-103.
文摘BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently leads to neuropsychiatric co-mplications,such as cognitive impairment,anxiety,and depressive symptoms,which adversely affect patients’quality of life and rehabilitation.Neutrophil ge-latinase-associated lipocalin(NGAL)has emerged as a potential biomarker for various conditions,including AIS.This study investigated the association bet-ween serum NGAL levels at admission and neuropsychiatric complications in patients with AIS.neuropsychiatric complications in patients with AIS.METHODS Between January 2022 and December 2023,150 patients with AIS were enrolled.Serum NGAL levels were measured at admission using an enzyme-linked immu-nosorbent assay.Cognitive function was assessed using the Mini-Mental State Examination,while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge.The relationship between serum NGAL levels and cognitive impairment,anxiety,and depressive symptoms was analyzed using multivariate logistic regression,adjusted for potential con-founders of age,sex,body mass index,smoking status,hypertension,diabetes mellitus,dyslipidemia,previous stroke,and stroke severity.RESULTS The mean age of the participants was 65.4±10.2 years,and 58%were males.Prevalence rates of cognitive impairment,anxiety,and depressive symptoms at discharge were 34.7%,28.0%,and 32.0%,respectively.Serum NGAL levels were significantly higher in patients with cognitive impairment(median:5.6 ng/mL vs 3.2 ng/mL,P<0.001),anxiety(median:5.1 ng/mL vs 3.5 ng/mL,P=0.002),and depressive symptoms(median:5.4 ng/mL vs 3.3 ng/mL,P<0.001),compared to those without these conditions.Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment[odds ratio(OR)=1.42,95%confidence interval(CI):1.18-1.71,P<0.001],anxiety(OR=1.28,95%CI:1.09-1.51,P=0.003),and depressive symptoms(OR=1.39,95%CI:1.16-1.67,P<0.001)after adjusting for potential confounders.CONCLUSION Elevated serum NGAL levels were independently associated with cognitive impairment,anxiety,and depressive symptoms in patients with AIS;and may function as potential biomarkers for patients at risk.
基金Supported by The Commissioned Project of the 2023 Elderly Appropriate Technology Special Fund of Jiangsu Geriatric Society,No.JSLY202302The Scientific Research Project of Jiangsu Provincial Health Commission,No.BJ21008+1 种基金The 2023 Specialized Disease Queue Research Project of Wuxi Medical Center,Nanjing Medical University,No.WMCC202311Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee,No.HB2023003.
文摘BACKGROUND Mild cognitive impairment(MCI)in elderly individuals is a transitional stage between normal cognition and dementia.Understanding the risk factors for MCI and identifying those at high risk are extremely important for the elderly population.AIM To analyze the risk factors for MCI in the elderly population and construct a clinical prediction model.METHODS Total 295 elderly individuals presenting with memory loss diagnosed at Wuxi People's Hospital between March 2021 and March 2024 were included.Comprehensive demographic,clinical,and serological data were collected for analysis.Participants were categorized into either an MCI group or a normal group based on their performance on the Montreal Cognitive Assessment Scale.An elaborate clinical predictive model was developed to predict the likelihood of MCI in stroke patients;its accuracy was evaluated using area under curve values and calibration curves.RESULTS The results of the study showed that old age,hypertension,diabetes,hyperlipidemia,smoking,high-salt diet,high-cholesterol diet,decreased red blood count,increased neutrophil lymphocyte ratio and increased low-density lipoprotein cholesterol were risk factors for the onset of MCI,with A high vitamin diet and elevated high-density lipoprotein cholesterol being protective factors.In addition,the prediction model constructed in this study exhibits good degrees of differentiation and calibration.CONCLUSION The risk factors for MCI are diverse.Early identification of individuals at high risk of MCI can better intervene and improve their quality of life of MCI patients.
基金Supported by National Key Research and Development Program of China,No.2019YFA0706200National Natural Science Foundation of China,No.82301738Natural Science Foundation of Hunan Province,No.2022JJ40701 and No.2022JJ40697.
文摘BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder(MDD).Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients.We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments.We also hypothesize that anxiety symptoms,especially psychic anxiety,is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors.AIM To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode.METHODS A comprehensive neurocognitive test battery assessed executive function,attention,processing speed,and memory in 162 medication-free MDD patients and 142 matched healthy controls.The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms,and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms.Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms,as well as their interactions,on cognitive impairments.RESULTS Among the depressive symptoms,sleep disturbances were associated with poorer executive function(P=0.004),lower processing speed(P=0.047),and memory impairments(P<0.001),and psychomotor retardation(PR)was associated with lower processing speed in patients with MDD(P=0.019).Notably,PR was found to mediate the impact of sleep disturbances on the processing speed.Regarding anxiety symptoms,psychic anxiety,rather than somatic anxiety,was associated with cognitive impairments in all aspects.Sleep disturbances mediated the effect of psychic anxiety on executive function[β=-0.013,BC CI(-0.027,-0.001)]and memory[β=-0.149,BC CI(-0.237,-0.063)],while PR mediated its effect on processing speed(β=-0.023,BC CI(-0.045,-0.004)].CONCLUSION Sleep disturbances may be a key predictor of poorer executive function,lower processing speed,and memory loss,while PR is crucial for lower processing speed during a depressive episode.Psychic anxiety contributes to all aspects of cognitive impairments,mediated by sleep disturbances and PR.
基金Supported by Jiangsu Province Phase 6"333 Project",No.BRA202201.
文摘BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.
基金Supported by the Science and Technology Project of Jiangsu Provincial Health Commission,No.ZDB2020003Nantong Science and Technology Program Project,No.MS22022035+1 种基金the Clinical Research Project of the Affiliated Hospital of Nantong University,No.LCYJB06Grant Fund for Research Hospitals in Jiangsu Province,No.YJXYY202204-YSB74.
文摘BACKGROUND Cognitive impairment,which manifests as a limited deterioration of specific functions associated with a particular disease,can lead to a general deterioration of the patient’s standard of living.Transcranial magnetic stimulation,a noninvasive neuromodulation technique,is frequently employed to treat cognitive impairment in neuropsychiatric disorders.AIM To analyzed the state of international research on neuromodulation methods for treating cognitive impairment between 2014 and 2023,with the aim of exploring the state of research worldwide and the most recent developments in this particular area.METHODS Articles and reviews pertaining to neuromodulation methods for cognitive impairment were examined using the web of science database between January 2014 and December 2023.Publications,nations,organizations,writers,journals,citations,and keywords data from the identified studies were systematically analyzed using the CiteSpace 6.3.R1 software.RESULTS A total of 2371 documents with 11750 authors and 9461 institutions,with some cooccurrences,were retrieved.The quantity of yearly publications is showing an increasing trend.The United States and China have emerged as important contributors.Among the institutes,Harvard University had the highest number of publications,while Rossi S an author who is frequently cited.Initially,the primary keywords included human motor cortex,placebo-controlled trials,and serotonin reuptake inhibitors.However,the emphasis gradually moved to substance use disorders,supplementary motor areas,neural mechanisms,and exercise.CONCLUSION The use of neuromodulation techniques to treat cognitive impairment has drawn interest from academics all around the world.This study revealed hotspots and new trends in the research of transcranial magnetic stimulation as a cognitive impairment rehabilitation treatment.These findings are hold significant potential to guide further research and thus promote transcranial magnetic stimulation as a treatment method for cognitive impairment.