The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Near-infrared brain functional characteristics of mild cognitive impairment with sleep disorders

BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.

Brain-derived neurotrophic factor alterations and cognitive decline in schizophrenia:Implications for early intervention

This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor(BDNF)levels in first-episode schizophrenia patients.The study revealed that higher levels of interleukin-6 and tumor necrosis factor-αcorrelated with reduced BDNF levels and poorer cognitive performance.Schizophrenia is a severe psy-chiatric disorder impacting approximately 1%of the global population,charac-terized by positive symptoms(hallucinations and delusions),negative symptoms(diminished motivation and cognitive impairments)and disorganized thoughts and behaviors.Emerging research highlights the role of BDNF as a potential biomarker for early diagnosis and therapeutic targeting.The findings from Cui et al’s study suggest that targeting neuroinflammation and enhancing BDNF levels may improve cognitive outcomes.Effective treatment approaches involve a com-bination of pharmacological and non-pharmacological interventions tailored to individual patient needs.Hence,monitoring cognitive and neuroinflammatory markers is essential for improving patient outcomes and quality of life.Conse-quently,this manuscript highlights the need for an integrated approach to schizo-phrenia management,considering both clinical symptoms and underlying neuro-biological changes.

Web-based cognitive interventions on subjective cognitive impairment in cancer survivors:A systemic review

Objective:Cancer survivors have experienced subjective cognitive impairment(SCI)when they received cancer diagnoses or treatments.Their psychosocial and emotional statuses were also impacted.With the advancement of web technologies,web-based cognitive interventions have been implemented in the management and the alleviation of the SCI,the psychosocial distress,and the emotional distress in cancer survivors.This review aimed to summarize the intervention contents of web-based cognitive interventions for SCI,and to explore the effects of the interventions on SCI,psychosocial status,and emotional health.Methods:Six databases(CINAHL Plus,Cochrane Library,Embase,APA PsycInfo,PubMed and CNKI)were searched from the establishment of databases up to December 2023.Literature references were also manually searched for related articles.Results:This review contained 21 studies that covered the contents of web-based cognitive interventions,such as computer-assisted cognitive training,online cognitive rehabilitation,cognitive behavior therapy with the Internet,telehealth physical exercise,and web-based mindfulness interventions.The effects of web-based cognitive interventions positively impacted SCI for cancer survivors.Also,these interventions showed varying degrees of effectiveness in alleviating psychosocial and emotional distresses.Conclusion:By summarizingfive types of cognitive intervention contents delivered via web technology,this review demonstrated that web-based cognitive interventions optimized SCI and overall psychosocial and emotional statuses for the cancer survivors.It is recommended that future research focus on the development of customized web-based cognitive interventions for individuals with SCI,along with their psychosocial and emotional statuses.

Effects of a Cocktail Supplement of Ginkgo Biloba and Acai Extract on Cognitive Symptoms of Parkinson’s Disease

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects and potential for dependency. This study investigates the effects of a natural supplement combination of Ginkgo Biloba and Acai Extract on cognitive symptoms in a 77-year-old male with PD. The participant underwent a three-month supplementation regimen, with cognitive function assessed using the Montreal Cognitive Assessment (MoCA) test before and after the intervention. The results indicated an improvement in cognitive scores, suggesting that the combination of Ginkgo Biloba and Acai Extract may offer a promising alternative or adjunct to conventional PD treatments. This study highlights the potential of natural supplements in managing PD symptoms and calls for further research with larger sample sizes to confirm these findings. Human data was performed in accordance with the Declaration of Helsinki by the Roxbury District IRB Board (IRB Number: IRB00011767).

Risk factors for cognitive impairment in patients with chronic kidney disease

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

Cognitive Jammers Assisted Covert Communication in Cognitive Radio Networks

In this work,we investigate the covert communication in cognitive radio(CR)networks with the existence of multiple cognitive jammers(CJs).Specifically,the secondary transmitter(ST)helps the primary transmitter(PT)to relay information to primary receiver(PR),as a reward,the ST can use PT's spectrum to transmit private information against the eavesdropper(Eve)under the help of one selected cognitive jammer(CJ).Meanwhile,we propose three jammer-selection schemes,namely,link-oriented jammer selection(LJS),min-max jammer selection(MMJS)and random jammer selection(RJS).For each scheme,we analyze the average covert throughput(ACT)and covert outage probability(COP).Our simulation results show that CJ is helpful to ST's covert communication,the expected minimum detection error probability and ACT can be significantly improved with the increase of false alarm of CJ.Moreover,the LJS scheme achieves best performance in ACT and COP,followed by RJS scheme,and MMJS scheme shows the worst performance.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty,characterized by the coexistence of cognitive impairment and physical frailty,represents a multifaceted challenge in the aging population.The role of cardiovascular risk factors in this complex interplay is not yet fully understood.AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia.METHODS A comprehensive approach was employed,with a total of 512 communitydwelling older persons aged 60 years and above,involving two cohorts of older persons from previous studies.Datasets related to cardiovascular risks,namely sociodemographic factors,and cardiovascular risk factors,including hypertension,diabetes,hypercholesterolemia,anthropometric characteristics and biochemical profiles,were pooled for analysis.Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score.Cardiovascular risk was determined using Framingham risk score.Statistical analyses were conducted using SPSS version 21.RESULTS Of the study participants,46.3%exhibited cognitive frailty.Cardiovascular risk factors including hypertension(OR:1.60;95%CI:1.12-2.30),low fat-free mass(OR:0.96;95%CI:0.94-0.98),high percentage body fat(OR:1.04;95%CI:1.02-1.06),high waist circumference(OR:1.02;95%CI:1.01-1.04),high fasting blood glucose(OR:1.64;95%CI:1.11-2.43),high Framingham risk score(OR:1.65;95%CI:1.17-2.31),together with sociodemographic factors,i.e.,being single(OR 3.38;95%CI:2.26-5.05)and low household income(OR 2.18;95%CI:1.44-3.30)were found to be associated with cognitive frailty.CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty,a prodromal stage of dementia.Early identification and management of cardiovascular risk factors,particularly among specific group of the population might mitigate the risk of cognitive frailty,hence preventing dementia.

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

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

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

Exploring the Association between Oral Microbiome and Mild Cognitive Impairment: A Narrative Review

Objective: Some studies have investigated the association between oral microbiome and mild cognitive impairment (MCI). However, there needs to be more narrative reviews synthesizing this evidence. This study aimed to bridge this gap in the current knowledge. Methods: A comprehensive search was conducted on PubMed (MEDLINE) to identify studies examining the association between the oral microbiome and MCI. Search parameters and inclusion criteria were clearly defined, encompassing terms related to the oral microbiome, MCI, and their association. Two authors independently selected relevant studies and performed data extraction. Result: Four studies were included. Two cohort studies and two case-control reported an association between the oral microbiome and MCI. Conclusion: Based on the evidence synthesized from the included studies, the review suggests an association between MCI and the oral microbiome. Specifically, all included studies identified significant differences in the abundance of specific microbial species between individuals with MCI and those with normal cognitive function, underscoring the potential role of these species in neuroinflammatory diseases.

Interconnected Challenges: Addressing the Bidirectional Relationship between Heart Failure and Cognitive Impairment through Targeted Intervention Strategies

This paper examines the bidirectional relationship between heart failure (HF) and cognitive impairment, underscoring the need for integrated intervention strategies to address these interconnected conditions effectively. Cognitive deficits often hinder the effective management of HF, leading to poorer treatment adherence and health outcomes, while the physiological stress of HF can further impair cognitive function, creating a complex interplay that complicates patient care. This study highlights the effectiveness of angiotensin-converting enzyme (ACE) inhibitors and cardiac resynchronization therapy (CRT) in improving both cardiac and cognitive functions. By targeting the underlying physiological and neurobiological mechanisms of HF, these therapies enhance patient outcomes, leading to better adherence to treatment regimens and overall quality of life. Furthermore, the findings suggest that regular cognitive assessments should be integrated into HF management protocols, enabling early identification of cognitive impairment and timely intervention. Incorporating ACE inhibitors and CRT into standard care practices not only addresses the complexities of managing HF and cognitive decline but also fosters a holistic approach to patient health. Ultimately, this multifaceted strategy has the potential to significantly improve health outcomes, enhance the quality of care, and support sustainable management of patients with heart failure and cognitive impairment.

Analysis of Chinese Xiehouyu from a Perspective of Cognitive Reference-Point

Xiehouyu (a two-part allegorical saying) is unique and refined, and the cultural load is rich and heavy. The use of Xiehouyu in verbal communication and literary works reflects the speaker’s cognitive ability and language skills of operating and blending cognitive concepts dynamically. Langacker’s reference-point theory has a high explanatory power and is a basic cognitive mode of human beings. This paper attempts to make a cognitive analysis of the structure and understanding of Xiehouyu by using reference-point theory, aiming at explaining its cognitive mechanism and meaning construction.

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).