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
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
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
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(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=[-0.1,1.9],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive functioning(SMD=0.07,94%CI=[-0.07,0.14],P=0.006).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.展开更多
BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emoti...BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emotional states is imperative.AIM To evaluate the efficacy of cognitive behavioral therapy(CBT)-based psychological interventions in improving the psychological well-being and quality of life(QoL)of patients with laryngeal carcinoma.METHODS This study enrolled 120 patients admitted from February 2022 to February 2024.The control group,comprising 50 participants,received standard supportive psychological care,while the research group,consisting 70 participants,underwent CBT-based interventions.Several clinical outcomes were systematically assessed that included postoperative recovery metrics(duration of tracheostomy and nasogastric tube dependence and length of hospitalization),psychological status(Self-Rating Anxiety Scale and Self-Rating Depression Scale),nutritional markers(serum albumin and hemoglobin levels),sleep quality(Self-Rating Scale of Sleep and Athens Insomnia Scale),and QoL(Functional Assessment of Cancer Therapy-Head and Neck).RESULTS The results demonstrated that the research group experienced superior outcomes,with significantly reduced durations of tracheostomy and nasogastric tube dependence,as well as shorter hospital stays,compared with the control group.Additionally,the research group exhibited markedly lower post-intervention Self-Rating Anxiety Scale,Self-Rating Depression Scale,Self-Rating Scale of Sleep,and Athens Insomnia Scale scores,along with minimal but higher change in serum albumin and hemoglobin levels compared with the control group.All five domains of Functional Assessment of Cancer Therapy-Head and Neck showed notable improvements in the research group,exceeding those observed in the control group.CONCLUSION CBT-based psychological support positively affects the mental well-being and QoL of patients with laryngeal carcinoma,highlighting its potential for broader clinical application.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitiv...With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitive impairment is characterized by chronicity,which not only seriously threatens the health of the elderly and reduces their quality of life,but also imposes a heavy burden on families and society due to its long course.Attaching importance to and strengthening the chronic disease management of elderly cognitive impairment has profound significance for delaying disease progression,improving patients’quality of life,and reducing the burden of family care.Therefore,this paper first comprehensively understands elderly cognitive impairment by briefly elaborating on its definition and characteristics;on this basis,it focuses on exploring effective strategies for the chronic disease management of elderly cognitive impairment,hoping to provide new ideas and methods for the management of this condition and offer useful references for relevant clinical research and practice.展开更多
Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We pr...Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.展开更多
Background:Health benefits have been reported for many physical activity(PA)interventions for improving fundamental movement skills(FMS)and cognitive function(CF),but the most effective type of PA interventions for em...Background:Health benefits have been reported for many physical activity(PA)interventions for improving fundamental movement skills(FMS)and cognitive function(CF),but the most effective type of PA interventions for emhancing FMS and CF in early childhood remain unknown.Thus,the study aimed to determine the effects of PA interventions in enhancing FMS and CF among young children and to establish the optimal types of PA interventions.Methods:Six electronic databases(PubMed,OVID,SPORTDiscus,Scopus,Web of Science,and Cochrane)were searched for studies from inception to March 17,2024.Randomized controlled trials(RCTs)were included in this study if they reported outcomes related to FMS,CF,or both associated with PA interventions.Effect sizes were calculated and performed as Hedges'g.The hierarchy of competing interventions was established using the surface under the cumulative ranking curve(SUCRA).Risk of bias was independently assessed using the Cochrane Riskof-Bias 2.Results:This analysis included 38 studies with 5237 young children,with sample sizes ranging from 32 to 897 participants.The types of PA interventions analyzed included active play/free play/unstructured PA(AP),general structured PA(GSPA),FMS-targeted PA programs(FMSprograms),cognitively-engaging PA programs(CPA),multilevel PA interventions(MPA),and exergaming.PA interventions had a large,pooled effect size for total FMS(g=0.96;95%CI:0.45-1.46;p<0.01;I^(2)=94%).For CF,a small-to-moderate pooled effect size was found(g=0.39;95%CI:0.18-0.60;p<0.01;I^(2)=88%).PA interventions longer than 3 months showed fewer benefits for FMS(p<0.01).The network meta-analysis showed that FMS-programs(standardized mean difference((SMD)=1.55,95%CI:0.98-2.11,SUCRA=98.3%)and GSPA(SMD=0.94,95%CI:0.05-1.85,SUCRA=69.8%)significantly improved total FMS compared to AP.For locomotor skills(LMS),exergaming ranked highest(SUCRA=79.3%),followed by FMS-programs(75.9%)and GSPA(61.6%).However,despite its top ranking,exergaming's effect estimate was not statistically significant(SMD=1.38,95%CI:-0.08 to 2.85).For object control skills(OCS),exergaming again ranked highest(SUCRA=91.9%)and showed the largest significant effect(SMD=2.38,95%CI:0.96-3.80),followed by FMS-programs(SUCRA=78.5%)and GSPA(SUCRA=53.7%).FMS-programs,GSPA,MPA,and UC also significantly improved OCS compared to AP.While no significant differences were observed across PA interventions for most CF domains,exergaming had a significant positive effect on working memory(SMD=1.41,95%CI:0.07-2.75).The certainty of evidence varied from low to moderate.Conclusion:These findings emphasize the importance of PA interventions in improving FMS and CF in early childhood.FMS-programs and GSPA appear to be the most effective approaches for enhancing total FMS,while exergaming showed the highest ranking for LMS and OCS,with a significant impact on OCS but uncertainty in LMS improvements.Additionally,exergaming had a positive effect on working memory,suggesting its potential cognitive benefits.展开更多
Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accom...Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.展开更多
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 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.
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 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(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=[-0.1,1.9],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive functioning(SMD=0.07,94%CI=[-0.07,0.14],P=0.006).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.
文摘BACKGROUND Approximately 30%of patients with head and neck cancer experience adverse effects caused by anxiety and depression.Considering the high prevalence,implementing customized interventions to ease adverse emotional states is imperative.AIM To evaluate the efficacy of cognitive behavioral therapy(CBT)-based psychological interventions in improving the psychological well-being and quality of life(QoL)of patients with laryngeal carcinoma.METHODS This study enrolled 120 patients admitted from February 2022 to February 2024.The control group,comprising 50 participants,received standard supportive psychological care,while the research group,consisting 70 participants,underwent CBT-based interventions.Several clinical outcomes were systematically assessed that included postoperative recovery metrics(duration of tracheostomy and nasogastric tube dependence and length of hospitalization),psychological status(Self-Rating Anxiety Scale and Self-Rating Depression Scale),nutritional markers(serum albumin and hemoglobin levels),sleep quality(Self-Rating Scale of Sleep and Athens Insomnia Scale),and QoL(Functional Assessment of Cancer Therapy-Head and Neck).RESULTS The results demonstrated that the research group experienced superior outcomes,with significantly reduced durations of tracheostomy and nasogastric tube dependence,as well as shorter hospital stays,compared with the control group.Additionally,the research group exhibited markedly lower post-intervention Self-Rating Anxiety Scale,Self-Rating Depression Scale,Self-Rating Scale of Sleep,and Athens Insomnia Scale scores,along with minimal but higher change in serum albumin and hemoglobin levels compared with the control group.All five domains of Functional Assessment of Cancer Therapy-Head and Neck showed notable improvements in the research group,exceeding those observed in the control group.CONCLUSION CBT-based psychological support positively affects the mental well-being and QoL of patients with laryngeal carcinoma,highlighting its potential for broader clinical application.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
文摘With the intensification of population aging in China,the problem of cognitive impairment in the elderly has become increasingly prominent,attracting widespread attention from all sectors of society.Geriatric cognitive impairment is characterized by chronicity,which not only seriously threatens the health of the elderly and reduces their quality of life,but also imposes a heavy burden on families and society due to its long course.Attaching importance to and strengthening the chronic disease management of elderly cognitive impairment has profound significance for delaying disease progression,improving patients’quality of life,and reducing the burden of family care.Therefore,this paper first comprehensively understands elderly cognitive impairment by briefly elaborating on its definition and characteristics;on this basis,it focuses on exploring effective strategies for the chronic disease management of elderly cognitive impairment,hoping to provide new ideas and methods for the management of this condition and offer useful references for relevant clinical research and practice.
基金supported by the National Natural Science Foundation of China(32172210)the Shandong Provincial Natural Science Foundation(ZR2025QC295).
文摘Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.
文摘Background:Health benefits have been reported for many physical activity(PA)interventions for improving fundamental movement skills(FMS)and cognitive function(CF),but the most effective type of PA interventions for emhancing FMS and CF in early childhood remain unknown.Thus,the study aimed to determine the effects of PA interventions in enhancing FMS and CF among young children and to establish the optimal types of PA interventions.Methods:Six electronic databases(PubMed,OVID,SPORTDiscus,Scopus,Web of Science,and Cochrane)were searched for studies from inception to March 17,2024.Randomized controlled trials(RCTs)were included in this study if they reported outcomes related to FMS,CF,or both associated with PA interventions.Effect sizes were calculated and performed as Hedges'g.The hierarchy of competing interventions was established using the surface under the cumulative ranking curve(SUCRA).Risk of bias was independently assessed using the Cochrane Riskof-Bias 2.Results:This analysis included 38 studies with 5237 young children,with sample sizes ranging from 32 to 897 participants.The types of PA interventions analyzed included active play/free play/unstructured PA(AP),general structured PA(GSPA),FMS-targeted PA programs(FMSprograms),cognitively-engaging PA programs(CPA),multilevel PA interventions(MPA),and exergaming.PA interventions had a large,pooled effect size for total FMS(g=0.96;95%CI:0.45-1.46;p<0.01;I^(2)=94%).For CF,a small-to-moderate pooled effect size was found(g=0.39;95%CI:0.18-0.60;p<0.01;I^(2)=88%).PA interventions longer than 3 months showed fewer benefits for FMS(p<0.01).The network meta-analysis showed that FMS-programs(standardized mean difference((SMD)=1.55,95%CI:0.98-2.11,SUCRA=98.3%)and GSPA(SMD=0.94,95%CI:0.05-1.85,SUCRA=69.8%)significantly improved total FMS compared to AP.For locomotor skills(LMS),exergaming ranked highest(SUCRA=79.3%),followed by FMS-programs(75.9%)and GSPA(61.6%).However,despite its top ranking,exergaming's effect estimate was not statistically significant(SMD=1.38,95%CI:-0.08 to 2.85).For object control skills(OCS),exergaming again ranked highest(SUCRA=91.9%)and showed the largest significant effect(SMD=2.38,95%CI:0.96-3.80),followed by FMS-programs(SUCRA=78.5%)and GSPA(SUCRA=53.7%).FMS-programs,GSPA,MPA,and UC also significantly improved OCS compared to AP.While no significant differences were observed across PA interventions for most CF domains,exergaming had a significant positive effect on working memory(SMD=1.41,95%CI:0.07-2.75).The certainty of evidence varied from low to moderate.Conclusion:These findings emphasize the importance of PA interventions in improving FMS and CF in early childhood.FMS-programs and GSPA appear to be the most effective approaches for enhancing total FMS,while exergaming showed the highest ranking for LMS and OCS,with a significant impact on OCS but uncertainty in LMS improvements.Additionally,exergaming had a positive effect on working memory,suggesting its potential cognitive benefits.
基金supported by The Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2023-00244901)(to RB)。
文摘Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.
