Traditional clinical subtype classifications(such as amnestic and non-amnestic mild cognitive impairment)rely on subjective interpretations of overlapping patterns of performance on cognitive tests,which may lead to u...Traditional clinical subtype classifications(such as amnestic and non-amnestic mild cognitive impairment)rely on subjective interpretations of overlapping patterns of performance on cognitive tests,which may lead to unreliable categorization.A more precise and objective classification of mild cognitive impairment subtypes can be achieved through data-driven clustering techniques.However,because previous studies have not restricted their cohorts to patients who have mild cognitive impairment with the pathology of Alzheimer’s disease,the nature of cognitive variability and its impact on disease progression in a strictly defined biomarker-positive preclinical Alzheimer’s disease cohort remains unknown.We examined cognitive heterogeneity among participants with mild cognitive impairment due to Alzheimer’s disease and evaluated its prognostic utility.Neuropsychological test data from 389 patients with mild cognitive impairment in whom the cerebrospinal fluid biomarker confirmed Alzheimer’s disease were obtained from the Alzheimer’s Disease Neuroimaging Initiative cohorts.Principal component analysis and model-based clustering were used to identify cognitive profiles,which were then validated through a 100-time bootstrap analysis.Pairwise comparisons tested for differences between the identified subgroups in participant characteristics,scores on cognitive and clinical outcomes,levels of cerebrospinal fluid biomarkers,and magnetic resonance imaging-derived brain volumes.Longitudinal analyses evaluated differences in rate of change of magnetic resonance imaging volumetric measurements and clinical outcomes over 48 months.Survival analysis assessed risk for conversion to dementia.Alpha-synuclein levels and white matter hyperintensity volumes were considered for sensitivity analysis.Two distinct cognitive profiles were identified:a“typical”group(56.04%of the sample)that demonstrated relatively poorer scores on memory testing than non-memory tests,and an“atypical”group(43.96%of the sample)with smaller differences between memory and non-memory measures,indicating a more uniform pattern of impairment across cognitive domains.While the groups had comparable levels of overall cognitive impairment and cerebrospinal fluid biomarkers of Alzheimer’s disease,the typical group displayed accelerated atrophy rates every 6 months across multiple brain regions(hippocampus:29.02 mm^(3),standard error[SE]=10.13,P=0.005;whole brain:1799.85 mm^(3),SE=781.57,P=0.023;entorhinal cortex:22.26 mm^(3),SE=11.15,P=0.048;fusiform gyrus:66.24 mm^(3),SE=28.53,P=0.021).Survival analysis revealed markedly higher dementia conversion risk(hazard ratio:1.70,95%confidence interval:1.27,2.27,P<0.001)and shorter progression time in the typical group.These findings persisted after controlling for comorbid pathologies.In conclusion,this data-driven approach identified two distinct cognitive subtypes of mild cognitive impairment due to Alzheimer’s disease that differed in their rates of clinical decline and neurodegeneration.These findings could be used to improve prognostic models and inform clinical trial stratification.展开更多
Ischemic stroke has a higher survival rate and is more likely to result in cognitive impairment than hemorrhagic stroke.The primary pathological mechanism underlying cognitive impairment involves dysfunction of neural...Ischemic stroke has a higher survival rate and is more likely to result in cognitive impairment than hemorrhagic stroke.The primary pathological mechanism underlying cognitive impairment involves dysfunction of neural circuits and damage to specific brain regions.This review aims to investigate the role of the hippocampus in cognitive impairment following a stroke.A review of the literature suggests that the hippocampus is a metabolically active structure that is easily involved in various metabolic states,such as hypoxia and hypoglycaemia.The functional changes in hippocampal cells associated with poststroke cognitive impairment mainly manifest as neuronal apoptosis,impaired synaptic plasticity,and decreased neurogenesis.The primary pathological mechanism of poststroke cognitive impairment involves a complex cascade of reactions,including neuroinflammatory activation,bursts of oxidative stress,and neuronal apoptosis induced by mitochondrial dysfunction.Interventional drugs for cognitive impairment after cerebral ischemia include neuroprotective drugs,traditional Chinese medicines and their extracts,and stem cell therapies.Many of these drugs have unique advantages,including the inhibition of neuroinflammation,the prevention of apoptosis,and the promotion of neurogenesis.They hold great potential for the prevention and treatment of cognitive impairment following cerebral ischemia.However,most current studies are animal experiments,and relatively few clinical studies exist.In future research,emphasis should be placed on interventions for cognitive impairment following cerebral ischemia.These findings offer novel perspectives for the treatment of cognitive impairment after cerebral ischemia.Finally,the role of hippocampal cell dysfunction in other diseases associated with cognitive decline is briefly discussed.The aim of this review is to provide researchers with a comprehensive overview of the role of the hippocampus in cognitive impairment and its intervention strategies.展开更多
The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It ha...The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).展开更多
Dementia is a growing global health burden,with mild cognitive impairment(MCI)serving as a critical transitional stage[1].Identifying the nutritional risk factors is crucial for prevention.While nutrition plays a key ...Dementia is a growing global health burden,with mild cognitive impairment(MCI)serving as a critical transitional stage[1].Identifying the nutritional risk factors is crucial for prevention.While nutrition plays a key role in preventing age-related diseases and staple foods are a major dietary source,existing research on cognitive function has predominantly emphasized whole-grain consumption.There is limited evidence regarding the effects of specific staple food types on MCI.展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Purpose: Individuals with mild cognitive impairment (MCI) frequently experience negative emotions, which are closely correlated with an accelerated rate of cognitive decline and the subsequent transition to a state of...Purpose: Individuals with mild cognitive impairment (MCI) frequently experience negative emotions, which are closely correlated with an accelerated rate of cognitive decline and the subsequent transition to a state of dementia. Despite networked cognitive training has been demonstrated to enhance cognitive function in MCI, its effectiveness for negative emotions is still unknown. This review aimed to exam the influences of networked cognitive training on negative emotions and quality of life in people with MCI. Methods: Searches for eligible studies were conducted using PubMed, Web of Science, EMBASE, Cochrane Library, Psyc INFO, CNKI, Wanfang database, VIP database, and Sinomed. The retrieval time limit was set from their inception to 17 December 2025. The articles were reviewed and extracted by two researchers, and their quality was evaluated using the Cochrane risk-of-bias assessment tool. Subsequently, a meta-analysis was carried out utilizing RevMan 5.4 software. Results: The review comprised 13 randomized controlled trials with 626 individuals. The meta-analysis demonstrated that networked cognitive training significantly improved depression (SMD = -0.36;95% CI [-0.73, -0.00];p = .050), anxiety (SMD = -0.32;95% CI [-0.57, -0.06];p < .050), and quality of life (MD = 2.54;95% CI [0.98, 4.10];p < .001). In terms of the comparison of apathy, the effect of intervention was unclear. Conclusions: From these meta-analysis results, networked cognitive training may help patients for MCI with their anxiety, depression, and overall quality of life. However, because there are so few randomized controlled trials available, the evidence regarding apathy is still ambiguous. More thorough randomized controlled trials with larger samples are necessary to verify the significance of networked cognitive training on apathy and to consolidate the findings.展开更多
Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes ...Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases.Aims To estimate the prevalence and incidence rates of two MCI subtypes—amnestic MCI(aMCI)and vascular cognitive impairment without dementia(VCIND)—and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort.Method This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large,community-dwelling cohort in China.Baseline lifestyle data were self-reported,while vascular and comorbid conditions were obtained from medical records and physical examinations.In total,3514 and 2051 individuals completed the baseline and 1-year follow-up assessments,respectively.Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline,respectively.Results Among our participants,aMCI and VCIND demonstrated prevalence of 14.83%and 2.71%,respectively,and annual incidence(per 1000 person-years)of 69.6 and 10.6,respectively.The risk factor for aMCI was age,whereas its protective factors were high education level,tea consumption and physical activity.Moreover,VCIND risk factors were age,hypertension and depression.The presence of endocrine disease,cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year.Conclusions MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented.Preventive strategies that promote brain activity and support healthy lifestyle choices are required.We identified modifiable factors for MCI in older individuals.The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI.展开更多
Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impair...Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.展开更多
Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult ...Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases.Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits.This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment.Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment,including cerebrovascular diseases,Alzheimer's disease,aging-related conditions,and issues related to anesthesia and surgery.The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized,and targeting AHN is considered a promising approach for treating cognitive impairment.However,the underlying mechanisms of this role are not yet fully understood,and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited,with a need for further development of treatment methods and detection techniques.By reviewing recent studies,we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories:immunity,energy metabolism,aging,and pathological states.In immunity-related mechanisms,abnormalities in meningeal,brain,and peripheral immunity can disrupt normal adult hippocampal neurogenesis.Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis.During aging,the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients.Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis.Among the current strategies used to enhance this form of neurogenesis,physical therapies such as exercise,transcutaneous electrical nerve stimulation,and enriched environments have proven effective.Dietary interventions,including energy intake restriction and nutrient optimization,have shown efficacy in both basic research and clinical trials.However,drug treatments,such as antidepressants and stem cell therapy,are primarily reported in basic research,with limited clinical application.The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention,and targeting the former may be an important strategy for treating the latter.However,the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear,and treatments are lacking.This highlights the need for greater focus on translating research findings into clinical practice.展开更多
Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes th...Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes the formation of carboxyhemoglobin,which reduces oxygen delivery to the tissues and organs and leads to hypoxia.Despite its well-documented toxicity,previous studies have confirmed that CO also acts as a signaling molecule in the body and plays important physiological roles(Motterlini and Otterbein,2010).展开更多
Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-infla...Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.展开更多
BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and of...BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and often the condition is prolonged,and the patients are prone to anxiety and uneasiness,which may be related to the harshness of the plateau environment,somatic discomfort due to the lack of oxygen,anxiety about the disease,and other factors.AIM To investigate the effects of cognitive behavioral therapy(CBT)on anxiety,sleep disorders,and hypoxia tolerance in patients with high-altitude respiratory diseases.METHODS A total of 2337 patients with high-altitude-related respiratory diseases treated at our hospital between November 2023 and January 2024 were selected as the study subjects.The subjects’pre-high-altitude residential altitude was approximately 1700 meters.They were divided into two groups.Both groups were given symptomatic treatment,and the control group implemented conventional nursing intervention,while the research group simultaneously conducted CBT intervention;assessed the degree of health knowledge of the two groups,and applied the Hamilton Anxiety Scale and the Pittsburgh Sleep Quality Index to assess the anxiety and sleep quality of the patients before and after the intervention,respectively.It also observed the length and efficiency of sleep,and detected the level of serum hypoxia inducible factor-1α,erythropoietin(EPO)and clinical intervention before and after intervention.EPO levels,and investigated satisfaction with the clinical intervention.RESULTS The rate of excellent health knowledge in the intervention group was 93.64%,which was higher than that in the control group(74.23%;P<0.05).Before the intervention,there was no significant difference in Hamilton Anxiety Scale and Pittsburgh Sleep Quality Index scores between the two groups(P>0.05),and after the intervention,the scores of the study group were significantly lower than those of the control group(P<0.05).There was no significant difference in sleep duration and sleep efficiency between the groups before the intervention(P>0.05),and after the intervention,the scores of the study group were significantly larger than those of the control group(P<0.05).There was no significant difference in serum hypoxia inducible factor-1αand EPO between the two groups before intervention(P>0.05),and both research groups were significantly lower than the control group after intervention(P<0.05).According to the questionnaire survey,the intervention satisfaction of the study group was 95.53%,which was higher than that of the control group(80.14%;P<0.05).CONCLUSION The CBT intervention in the treatment of patients with high-altitude-related respiratory diseases helps improve patients'health knowledge,relieve anxiety,improve sleep quality and hypoxia tolerance,and improve nursing satisfaction.展开更多
Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its prec...Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.展开更多
Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In th...Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.展开更多
The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests suc...The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.展开更多
Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structu...Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.展开更多
Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agen...Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agent linked to cognitive decline,this study investigated whether chronic,low-dose methanol exposure could recapitulate AD-like pathology and cognitive deficits in rhesus monkey,thereby establishing a nonhuman primate animal model driven by this environmental-metabolic insult.Methods:Adult rhesus monkeys received low-concentration methanol for 9 months.Behavioral tests for cognition,locomotion,sleep,and vision were conducted.Postmortem analyses involved histopathological examination,immunohistochemistry,immunofluorescence,and Western blot to evaluate neuronal integrity,microglial activation,and the expression of key proteins associated with AD(amyloid-β[Aβ],phosphorylated tau,TAR DNA-binding protein 43[TDP-43])and cellular stress(synaptic markers,mitochondrial fission,autophagy,and apoptosis-related proteins).Results:Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits.Neuropathology revealed brain atrophy,neuronal loss,synaptic damage,microglial activation,and mitochondrial structural disorganization.Critically,the exposed animals exhibited hallmark AD-like molecular alterations,including increased Aβ deposition,tau hyperphosphorylation,and TDP-43 dysregulation.Furthermore,neurotoxicity was associated with elevated urinary formaldehyde,enhanced mitochondrial fission,increased autophagy,and elevated apoptosis.Conclusion:Chronic low-dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD-like neuropathological features.This model,driven by endogenous formaldehyde toxicity,effectively mimics key aspects of sporadic AD.Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.展开更多
Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the...Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the presynaptic nerve terminal.It serves as a key molecule to modulate endocytosis and exocytosis.However,under pathological conditions,α-synuclein adopts different conformations,being converted into toxic oligomers.The molecular weight ofα-synuclein oligomers ranges from 25 to 180 kDa,and they do not form filamentous aggregates ofα-synuclein.Subsequently,α-synuclein oligomers change to aggregates,including protofibrils and fibrils(Miki et al.,2022).This process has been implicated in the pathogenesis of neurodegenerative diseases collectively termed synucleinopathies,which include Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy(MSA).展开更多
Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear ...Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear and contentious.This study offered a comprehensive review and meta-analysis of research published until June 2024,analyzing the effects of multivitamins on various cognitive functions in individuals aged 65 and older.We included ten randomized controlled trials encompassing 13,600 participants from multiple databases.These studies evaluated the impact of multivitamins on reasoning,memory,learning,visual perception,idea production,cognitive speed,psychomotor abilities,and higher cognitive functions.Our meta-analysis revealed that multivitamins significantly enhanced delayed free recall (standardized mean difference(SMD)=0.09,95%confidence interval(CI)=[0.05,0.13],P<0.0001).However,they had no substantial effects on immediate free recall(SMD=0.85,95%CI=[-0.18,1.90],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive speed(SMD=0.34,95%CI=[-0.07,0.74],P=0.11).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.展开更多
Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LP...Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LPS)-induced septic rat model,revealed the hyperphosphorylation of tau and cognitive impairments,accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats.Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10)as a central regulator of neuroinflammation.LPS triggered CXCL10 secretion in astrocytes,and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits.Recombinant CXCL10 recapitulated these effects in vitro and in vivo.Blocking CXCL10–CXCR3 interaction reversed tau phosphorylation,synaptic impairment,and cognitive decline.Mechanistically,CXCL10–CXCR3 interaction activated CaMKII,driving tau hyperphosphorylation,while CaMKII inhibition restored synaptic protein levels.These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10–CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.展开更多
基金funded by Shanghai Baiyulan Pujiang Project(No.24PJD087)funded by the National Natural Science Foundation of China(No.12401347)+5 种基金Shanghai“Science and Technology Innovation Action Plan”Computational Biology Key Project(Nos.23JS1400500 and 23JS1400800)Chinese MOE Foundation on Humanities and Social Sciences(No.23YJC910006)the Natural Science Foundation of Shanghai(No.24ZR1420400)MWB was funded by NIH/NIA(Nos.R01AG082073,R01AG079280,and P30AG062429)HHF was funded by NIH/NIA(Nos.U19AG079774-01,R01AG061146,P30AG062429,R01AG076634-01,CIHR 137794)funded by NIH/NIA R01AG064002,P30AG062429,R01AG076634,and the Epstein Family Alzheimer’s Research Collaboration.
文摘Traditional clinical subtype classifications(such as amnestic and non-amnestic mild cognitive impairment)rely on subjective interpretations of overlapping patterns of performance on cognitive tests,which may lead to unreliable categorization.A more precise and objective classification of mild cognitive impairment subtypes can be achieved through data-driven clustering techniques.However,because previous studies have not restricted their cohorts to patients who have mild cognitive impairment with the pathology of Alzheimer’s disease,the nature of cognitive variability and its impact on disease progression in a strictly defined biomarker-positive preclinical Alzheimer’s disease cohort remains unknown.We examined cognitive heterogeneity among participants with mild cognitive impairment due to Alzheimer’s disease and evaluated its prognostic utility.Neuropsychological test data from 389 patients with mild cognitive impairment in whom the cerebrospinal fluid biomarker confirmed Alzheimer’s disease were obtained from the Alzheimer’s Disease Neuroimaging Initiative cohorts.Principal component analysis and model-based clustering were used to identify cognitive profiles,which were then validated through a 100-time bootstrap analysis.Pairwise comparisons tested for differences between the identified subgroups in participant characteristics,scores on cognitive and clinical outcomes,levels of cerebrospinal fluid biomarkers,and magnetic resonance imaging-derived brain volumes.Longitudinal analyses evaluated differences in rate of change of magnetic resonance imaging volumetric measurements and clinical outcomes over 48 months.Survival analysis assessed risk for conversion to dementia.Alpha-synuclein levels and white matter hyperintensity volumes were considered for sensitivity analysis.Two distinct cognitive profiles were identified:a“typical”group(56.04%of the sample)that demonstrated relatively poorer scores on memory testing than non-memory tests,and an“atypical”group(43.96%of the sample)with smaller differences between memory and non-memory measures,indicating a more uniform pattern of impairment across cognitive domains.While the groups had comparable levels of overall cognitive impairment and cerebrospinal fluid biomarkers of Alzheimer’s disease,the typical group displayed accelerated atrophy rates every 6 months across multiple brain regions(hippocampus:29.02 mm^(3),standard error[SE]=10.13,P=0.005;whole brain:1799.85 mm^(3),SE=781.57,P=0.023;entorhinal cortex:22.26 mm^(3),SE=11.15,P=0.048;fusiform gyrus:66.24 mm^(3),SE=28.53,P=0.021).Survival analysis revealed markedly higher dementia conversion risk(hazard ratio:1.70,95%confidence interval:1.27,2.27,P<0.001)and shorter progression time in the typical group.These findings persisted after controlling for comorbid pathologies.In conclusion,this data-driven approach identified two distinct cognitive subtypes of mild cognitive impairment due to Alzheimer’s disease that differed in their rates of clinical decline and neurodegeneration.These findings could be used to improve prognostic models and inform clinical trial stratification.
基金supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX25_3785(to JY).
文摘Ischemic stroke has a higher survival rate and is more likely to result in cognitive impairment than hemorrhagic stroke.The primary pathological mechanism underlying cognitive impairment involves dysfunction of neural circuits and damage to specific brain regions.This review aims to investigate the role of the hippocampus in cognitive impairment following a stroke.A review of the literature suggests that the hippocampus is a metabolically active structure that is easily involved in various metabolic states,such as hypoxia and hypoglycaemia.The functional changes in hippocampal cells associated with poststroke cognitive impairment mainly manifest as neuronal apoptosis,impaired synaptic plasticity,and decreased neurogenesis.The primary pathological mechanism of poststroke cognitive impairment involves a complex cascade of reactions,including neuroinflammatory activation,bursts of oxidative stress,and neuronal apoptosis induced by mitochondrial dysfunction.Interventional drugs for cognitive impairment after cerebral ischemia include neuroprotective drugs,traditional Chinese medicines and their extracts,and stem cell therapies.Many of these drugs have unique advantages,including the inhibition of neuroinflammation,the prevention of apoptosis,and the promotion of neurogenesis.They hold great potential for the prevention and treatment of cognitive impairment following cerebral ischemia.However,most current studies are animal experiments,and relatively few clinical studies exist.In future research,emphasis should be placed on interventions for cognitive impairment following cerebral ischemia.These findings offer novel perspectives for the treatment of cognitive impairment after cerebral ischemia.Finally,the role of hippocampal cell dysfunction in other diseases associated with cognitive decline is briefly discussed.The aim of this review is to provide researchers with a comprehensive overview of the role of the hippocampus in cognitive impairment and its intervention strategies.
文摘The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).
基金supported by the National Natural Science Foundation of China(81903416).
文摘Dementia is a growing global health burden,with mild cognitive impairment(MCI)serving as a critical transitional stage[1].Identifying the nutritional risk factors is crucial for prevention.While nutrition plays a key role in preventing age-related diseases and staple foods are a major dietary source,existing research on cognitive function has predominantly emphasized whole-grain consumption.There is limited evidence regarding the effects of specific staple food types on MCI.
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
文摘Purpose: Individuals with mild cognitive impairment (MCI) frequently experience negative emotions, which are closely correlated with an accelerated rate of cognitive decline and the subsequent transition to a state of dementia. Despite networked cognitive training has been demonstrated to enhance cognitive function in MCI, its effectiveness for negative emotions is still unknown. This review aimed to exam the influences of networked cognitive training on negative emotions and quality of life in people with MCI. Methods: Searches for eligible studies were conducted using PubMed, Web of Science, EMBASE, Cochrane Library, Psyc INFO, CNKI, Wanfang database, VIP database, and Sinomed. The retrieval time limit was set from their inception to 17 December 2025. The articles were reviewed and extracted by two researchers, and their quality was evaluated using the Cochrane risk-of-bias assessment tool. Subsequently, a meta-analysis was carried out utilizing RevMan 5.4 software. Results: The review comprised 13 randomized controlled trials with 626 individuals. The meta-analysis demonstrated that networked cognitive training significantly improved depression (SMD = -0.36;95% CI [-0.73, -0.00];p = .050), anxiety (SMD = -0.32;95% CI [-0.57, -0.06];p < .050), and quality of life (MD = 2.54;95% CI [0.98, 4.10];p < .001). In terms of the comparison of apathy, the effect of intervention was unclear. Conclusions: From these meta-analysis results, networked cognitive training may help patients for MCI with their anxiety, depression, and overall quality of life. However, because there are so few randomized controlled trials available, the evidence regarding apathy is still ambiguous. More thorough randomized controlled trials with larger samples are necessary to verify the significance of networked cognitive training on apathy and to consolidate the findings.
基金supported by the Major Project of Wuxi Municipal Health Commission[grant number:Z202406]the Jiangsu Commission of Health Program[grant number:M2024010]+3 种基金the National Key Research and Development Program[grant number:2022YFC3600600]the China Ministry of Science and Technology grants[grant number:2009BAI77B03]the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support[grant number:20172029]the Innovative Research Team of High-level Local Universities in Shanghai[grant number:ZDCX20211201].
文摘Background As the population in China rapidly ages,the prevalence of mild cognitive impairment(MCI)is increasing considerably.However,the causes of MCI vary.The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases.Aims To estimate the prevalence and incidence rates of two MCI subtypes—amnestic MCI(aMCI)and vascular cognitive impairment without dementia(VCIND)—and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort.Method This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large,community-dwelling cohort in China.Baseline lifestyle data were self-reported,while vascular and comorbid conditions were obtained from medical records and physical examinations.In total,3514 and 2051 individuals completed the baseline and 1-year follow-up assessments,respectively.Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline,respectively.Results Among our participants,aMCI and VCIND demonstrated prevalence of 14.83%and 2.71%,respectively,and annual incidence(per 1000 person-years)of 69.6 and 10.6,respectively.The risk factor for aMCI was age,whereas its protective factors were high education level,tea consumption and physical activity.Moreover,VCIND risk factors were age,hypertension and depression.The presence of endocrine disease,cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year.Conclusions MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented.Preventive strategies that promote brain activity and support healthy lifestyle choices are required.We identified modifiable factors for MCI in older individuals.The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI.
基金supported by Applied Basic Research Foundation of Yunnan Province,Nos.202301AS070045,202101AY070001-115(to XY and BL)National Natural Science Foundation of China,No.81960242(to XY)。
文摘Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.
基金supported by Technological Innovation 2030-Major Projects of“Brain Science and Brain-like Research,”No.2022ZD0206200(to XG)the National Natural Science Foundation of China,No.82371245(to SJ),82102246(to XD),81701092(to XG)+2 种基金the Natural Science Foundation of Shandong Province,No.ZR2020MH129(to SJ)Shanghai Municipal Key Clinical Specialty,No.shslczdzk03601Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation,No.20DZ2254200。
文摘Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases.Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits.This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment.Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment,including cerebrovascular diseases,Alzheimer's disease,aging-related conditions,and issues related to anesthesia and surgery.The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized,and targeting AHN is considered a promising approach for treating cognitive impairment.However,the underlying mechanisms of this role are not yet fully understood,and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited,with a need for further development of treatment methods and detection techniques.By reviewing recent studies,we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories:immunity,energy metabolism,aging,and pathological states.In immunity-related mechanisms,abnormalities in meningeal,brain,and peripheral immunity can disrupt normal adult hippocampal neurogenesis.Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis.During aging,the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients.Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis.Among the current strategies used to enhance this form of neurogenesis,physical therapies such as exercise,transcutaneous electrical nerve stimulation,and enriched environments have proven effective.Dietary interventions,including energy intake restriction and nutrient optimization,have shown efficacy in both basic research and clinical trials.However,drug treatments,such as antidepressants and stem cell therapy,are primarily reported in basic research,with limited clinical application.The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention,and targeting the former may be an important strategy for treating the latter.However,the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear,and treatments are lacking.This highlights the need for greater focus on translating research findings into clinical practice.
基金supported in part by the NIH(R01NS113556,to KA).
文摘Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes the formation of carboxyhemoglobin,which reduces oxygen delivery to the tissues and organs and leads to hypoxia.Despite its well-documented toxicity,previous studies have confirmed that CO also acts as a signaling molecule in the body and plays important physiological roles(Motterlini and Otterbein,2010).
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2022A1515010783)the Sustainable Development Program of Shenzhen Science and Technology Major Program(No.KCXFZ20240903093925033)+4 种基金the Guangdong Provincial Special Project in Science and Technology(No.2021A05240)the Special Project in Key Fields of Guangdong Provincial Higher Education Institutions(No.2021ZDZX2064)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(No.JCYJ20220530162014032)the Zhanjiang Marine Youth Talent Innovation Project(No.2022E05010)the Program for Scientific Research Start-up Funds of Guangdong Ocean University(Nos.R18008,060302042201)。
文摘Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.
基金Supported by Army Logistics Department Health Bureau Project,No.QJGYXYJZX-012.
文摘BACKGROUND Due to the dry and cold climate,the obvious temperature difference between day and night,and the low oxygen content of the air in the plateau area,people are prone to upper respiratory tract diseases,and often the condition is prolonged,and the patients are prone to anxiety and uneasiness,which may be related to the harshness of the plateau environment,somatic discomfort due to the lack of oxygen,anxiety about the disease,and other factors.AIM To investigate the effects of cognitive behavioral therapy(CBT)on anxiety,sleep disorders,and hypoxia tolerance in patients with high-altitude respiratory diseases.METHODS A total of 2337 patients with high-altitude-related respiratory diseases treated at our hospital between November 2023 and January 2024 were selected as the study subjects.The subjects’pre-high-altitude residential altitude was approximately 1700 meters.They were divided into two groups.Both groups were given symptomatic treatment,and the control group implemented conventional nursing intervention,while the research group simultaneously conducted CBT intervention;assessed the degree of health knowledge of the two groups,and applied the Hamilton Anxiety Scale and the Pittsburgh Sleep Quality Index to assess the anxiety and sleep quality of the patients before and after the intervention,respectively.It also observed the length and efficiency of sleep,and detected the level of serum hypoxia inducible factor-1α,erythropoietin(EPO)and clinical intervention before and after intervention.EPO levels,and investigated satisfaction with the clinical intervention.RESULTS The rate of excellent health knowledge in the intervention group was 93.64%,which was higher than that in the control group(74.23%;P<0.05).Before the intervention,there was no significant difference in Hamilton Anxiety Scale and Pittsburgh Sleep Quality Index scores between the two groups(P>0.05),and after the intervention,the scores of the study group were significantly lower than those of the control group(P<0.05).There was no significant difference in sleep duration and sleep efficiency between the groups before the intervention(P>0.05),and after the intervention,the scores of the study group were significantly larger than those of the control group(P<0.05).There was no significant difference in serum hypoxia inducible factor-1αand EPO between the two groups before intervention(P>0.05),and both research groups were significantly lower than the control group after intervention(P<0.05).According to the questionnaire survey,the intervention satisfaction of the study group was 95.53%,which was higher than that of the control group(80.14%;P<0.05).CONCLUSION The CBT intervention in the treatment of patients with high-altitude-related respiratory diseases helps improve patients'health knowledge,relieve anxiety,improve sleep quality and hypoxia tolerance,and improve nursing satisfaction.
基金supported by the National Natural Science Foundation of China(Nos.82430116 and 82574622)the Special Fund of Central Committee High Level Chinese Medicine Hospital(Nos.DZMG-LJRC-0014,DZMG-ZJXY-23013)+1 种基金Chinese Medicine Inheritance and Innovation“Thousand Million”Talents Project(Qihuang Project 2021)Qihuang Scholarsthe Medical and Health Industry Development Project of Tongzhou District(2023).
文摘Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.
基金supported by the National Natural Science Foundation of China,No.82201626(to CC)the Natural Science Foundation of LiaoningProvince,No.2022-MS-442(to CC)the Dalian Municipal Medical Key Specialty Climbing Project,No.2024ZZ040(to MZ).
文摘Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
文摘The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.
文摘Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01+1 种基金PUMC Innovation Fund for Graduate Students,Grant/Award Number:2017-1001-07National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:The absence of effective animal models for sporadic Alzheimer's disease(AD)remains a pivotal barrier to therapy development.Because methanol metabolism produces endogenous formaldehyde,a neurotoxic agent linked to cognitive decline,this study investigated whether chronic,low-dose methanol exposure could recapitulate AD-like pathology and cognitive deficits in rhesus monkey,thereby establishing a nonhuman primate animal model driven by this environmental-metabolic insult.Methods:Adult rhesus monkeys received low-concentration methanol for 9 months.Behavioral tests for cognition,locomotion,sleep,and vision were conducted.Postmortem analyses involved histopathological examination,immunohistochemistry,immunofluorescence,and Western blot to evaluate neuronal integrity,microglial activation,and the expression of key proteins associated with AD(amyloid-β[Aβ],phosphorylated tau,TAR DNA-binding protein 43[TDP-43])and cellular stress(synaptic markers,mitochondrial fission,autophagy,and apoptosis-related proteins).Results:Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits.Neuropathology revealed brain atrophy,neuronal loss,synaptic damage,microglial activation,and mitochondrial structural disorganization.Critically,the exposed animals exhibited hallmark AD-like molecular alterations,including increased Aβ deposition,tau hyperphosphorylation,and TDP-43 dysregulation.Furthermore,neurotoxicity was associated with elevated urinary formaldehyde,enhanced mitochondrial fission,increased autophagy,and elevated apoptosis.Conclusion:Chronic low-dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD-like neuropathological features.This model,driven by endogenous formaldehyde toxicity,effectively mimics key aspects of sporadic AD.Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.
基金supported by Hirosaki University Priority Research Grant for Future Innovation(to YM),JSPS KAKENHI Grant Numbers 24K10654(to YM)and 23K24209(to KW)the Collaborative Research Project of the Brain Research Institute,Niigata University(to YM).
文摘Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the presynaptic nerve terminal.It serves as a key molecule to modulate endocytosis and exocytosis.However,under pathological conditions,α-synuclein adopts different conformations,being converted into toxic oligomers.The molecular weight ofα-synuclein oligomers ranges from 25 to 180 kDa,and they do not form filamentous aggregates ofα-synuclein.Subsequently,α-synuclein oligomers change to aggregates,including protofibrils and fibrils(Miki et al.,2022).This process has been implicated in the pathogenesis of neurodegenerative diseases collectively termed synucleinopathies,which include Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy(MSA).
基金supported by the Fundamental Research Funds for the Central Universities(2042023gf0003)Hubei Provincial Natural Science Foundation of China(2024AFD126)National Key Research and Development Program of China(2023YFF1104404).
文摘Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear and contentious.This study offered a comprehensive review and meta-analysis of research published until June 2024,analyzing the effects of multivitamins on various cognitive functions in individuals aged 65 and older.We included ten randomized controlled trials encompassing 13,600 participants from multiple databases.These studies evaluated the impact of multivitamins on reasoning,memory,learning,visual perception,idea production,cognitive speed,psychomotor abilities,and higher cognitive functions.Our meta-analysis revealed that multivitamins significantly enhanced delayed free recall (standardized mean difference(SMD)=0.09,95%confidence interval(CI)=[0.05,0.13],P<0.0001).However,they had no substantial effects on immediate free recall(SMD=0.85,95%CI=[-0.18,1.90],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive speed(SMD=0.34,95%CI=[-0.07,0.74],P=0.11).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.
基金supported by Grants from the National Natural Science Foundation of China(82330041 and 82201326)the China Postdoctoral Research Foundation(GZC20230898)the Science and Technology Innovation Team Project to Xiaochuan Wang from the Department of Science and Technology of Hubei Province(2022-72-18).
文摘Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LPS)-induced septic rat model,revealed the hyperphosphorylation of tau and cognitive impairments,accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats.Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10)as a central regulator of neuroinflammation.LPS triggered CXCL10 secretion in astrocytes,and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits.Recombinant CXCL10 recapitulated these effects in vitro and in vivo.Blocking CXCL10–CXCR3 interaction reversed tau phosphorylation,synaptic impairment,and cognitive decline.Mechanistically,CXCL10–CXCR3 interaction activated CaMKII,driving tau hyperphosphorylation,while CaMKII inhibition restored synaptic protein levels.These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10–CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.
