BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease.Long-term seizures can seriously affect the prognosis and quality of life of patients.Electroencephalogra...BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease.Long-term seizures can seriously affect the prognosis and quality of life of patients.Electroencephalogram(EEG)is the simplest way to diagnose epilepsy,and plays an important role in predicting seizures and guiding medication.AIM To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform discharges.METHODS From January 2017 to June 2020,10 patients with post-stroke epilepsy in our hospital were included.The clinical,imaging,and EEG characteristics were collected.The stroke location,seizure type,and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively analyzed.RESULTS In all 10 patients,epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage;these manifested as sharp wave,sharp-wave complex,or spike discharges in the anterior head lead of the side opposite to the lesion.CONCLUSION In EEG,epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.展开更多
Background:To investigate the effects of acupuncture on post-stroke limb spasm model rats and the underlying mechanism.Methods:A total of 50 Sprague-Dawley rats were randomly divided into three groups,Control group(10...Background:To investigate the effects of acupuncture on post-stroke limb spasm model rats and the underlying mechanism.Methods:A total of 50 Sprague-Dawley rats were randomly divided into three groups,Control group(10),Model group(20)and Zhishen Tiaoxing(ZSTX)acupuncture group(20).Middle cerebral artery occlusion was conducted in SD rats to establish post-stroke limb spasm rats,which were treated with ZSTX acupuncture.Behavioral assays were determined by the Narrow ally test,the limb muscle tension was detected by the BL-420S test system,and infarct volume was assessed after the cerebral infarction by 2,3,5-triphenyltetrazolium chloride staining.Heterogeneous neurotransmitterγ-aminobutyric acid(GABA)and its receptors GABAA and GABAB in the cerebral cortex of the infarct area were determined by immunofluorescence assay.The release of Trkb and K-Cl cotransporter isoform 2 was detected by an immunofluorescence double labeling study.Western Blot was utilized to measure the expression of BDNF and Trkb.Results:The results showed that the behavioral assays in post-stroke limb spasm rats were significantly improved by the treatment of ZSTX acupuncture.14 days of ZSTX acupuncture can effectively inhibit muscle tone and decrease Infarct volume,which was measured with BL-420S biological function experiment system and triphenyltetrazolium chloride.Meanwhile,the results of Double-Label Immunofluorescence Assays showed that ZSTX acupuncture improved the expression of GABA,GABAA,GABAB,BDNF,and K-Cl cotransporter isoform 2.Double-Label Immunofluorescence Assays and WB results showed that 14 days ZSTX acupuncture declined the expression of Trkb.Conclusions:Our results suggest that 14 days of ZSTX acupuncture can significantly improve post-stroke limb spasm.Meanwhile,the pathogenesis of post-stroke limb spasm and the efficacy of ZSTX acupuncture involve metabolic pathways of neurotransmitters,and electro-acupuncture can treat post-stroke limb spasm by regulating BDNF/Trkb-KCC2 signaling pathway.展开更多
BACKGROUND Post-stroke depression(PSD)is a common and debilitating condition affecting stroke survivors,significantly impacting their recovery and overall quality of life.AIM To assess the effects of early PSD screeni...BACKGROUND Post-stroke depression(PSD)is a common and debilitating condition affecting stroke survivors,significantly impacting their recovery and overall quality of life.AIM To assess the effects of early PSD screening on functional outcomes,quality of life,and mortality.METHODS From an initial pool of 1065 articles,6 studies met the inclusion criteria and were selected for analysis.Functional outcomes were measured using the functional independence measure(FIM).RESULTS The analysis revealed a significant improvement in FIM scores for a PSD scree-ning group compared to controls[standardized mean difference(SMD)=8.90,95%confidence interval(CI):4.65-13.15,P<0.01].Quality of life was assessed using the Stroke-Specific Quality of Life Scale,with the screening group showing significantly higher scores(SMD=20.83,95%CI:15.27-26.38,P<0.01).Mortality analysis indicated a reduction in five-year mortality rates for the PSD screening group.CONCLUSION Early PSD screening enhances functional recovery,improves quality of life,and reduces mortality rates in stroke survivors.Thus,integrating PSD screening into routine stroke care improves long-term outcomes for patients.展开更多
BACKGROUND Stroke has become one of the most serious life-threatening diseases due to its high morbidity,disability,recurrence and mortality rates.AIM To explore the intervention effect of multi-disciplinary treatment...BACKGROUND Stroke has become one of the most serious life-threatening diseases due to its high morbidity,disability,recurrence and mortality rates.AIM To explore the intervention effect of multi-disciplinary treatment(MDT)extended nursing model on negative emotions and quality of life of young patients with post-stroke.METHODS A total of 60 young stroke patients who were hospitalized in the neurology department of our hospital from January 2020 to December 2021 were selected and randomly divided into a control group and an experimental group,with 30 patients in each group.The control group used the conventional care model and the experimental group used the MDT extended nursing model.After the inhospital and 3-mo post-discharge interventions,the differences in negative emotions and quality of life scores between the two groups were evaluated and analyzed at the time of admission,at the time of discharge and after discharge,respectively.RESULTS There are no statistically significant differences in the negative emotions scores between the two groups at admission,while there are statistically significant differences in the negative emotions scores within each group at admission and discharge,at discharge and post-discharge,and at discharge and post-discharge.In addition,the negative emotions scores were all statistically significant at discharge and after discharge when compared between the two groups.There was no statistically significant difference in quality of life scores at the time of admission between the two groups,and the difference between quality of life scores at the time of admission and discharge,at the time of discharge and post-discharge,and at the time of admission and post-discharge for each group of patients was statistically significant.CONCLUSION The MDT extended nursing mode can improve the negative emotion of patients and improve their quality of life.Therefore,it can be applied in future clinical practice and is worthy of promotion.展开更多
Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The st...Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.展开更多
In this commentary,we summarize some of the key points of the original paper“Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality,complications,or outcomes”a...In this commentary,we summarize some of the key points of the original paper“Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality,complications,or outcomes”and offer support for the proposed results.Specifically,we address how early percutaneous endoscopic gastrostomy(PEG)tube placement may reduce hospital length of stay and costs.We also discuss topics related to the article including PEG weaning and post-stroke nutritional formulation.However,we note that concerns purported by previous studies that early PEG placement may worsen outcomes are not fully addressed,and further research is needed.展开更多
In this work,we intended to connect clinimetrics with holism in traditional Chinese medicine towards multidimensional assessment of post-stroke sequelae in real-world setting,as a bridge between inheritance and innova...In this work,we intended to connect clinimetrics with holism in traditional Chinese medicine towards multidimensional assessment of post-stroke sequelae in real-world setting,as a bridge between inheritance and innovation.Firstly,a systematic search of current evidence that supported integrated treatment of traditional Chinese and Western medicine for post-stroke sequelae sufferers was performed.Secondly,on the basis of available evidence,we presented couples of implications.Lastly,as psychosomatic perspective is one of the main academic paradigms of traditional Chinese medicine holism,we chiefly proposed comprehensive assessment for both motor and non-motor severities to probably match consonance with traditional Chinese medicine practice that treats psycho-/somatic-complains simultaneously.展开更多
Background: Dementia is a condition with progressive cognitive dysfunction and manifestation of both behavioral and psychosocial symptoms. Non-pharmacological measures such as music therapy are gaining importance sinc...Background: Dementia is a condition with progressive cognitive dysfunction and manifestation of both behavioral and psychosocial symptoms. Non-pharmacological measures such as music therapy are gaining importance since efficacy and safety of people with dementia have been questionable for pharmacological measures. Patient’s response to music is persistent even in the later stage of dementia. Aim: This rapid review aims to identify, analyze, evaluate, and summarize the best available evidence on the effectiveness of music-based therapeutic interventions among people with dementia. Method: CINAHL Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened the literature search results. Effectiveness, music-based therapeutic intervention, dementia, Alzheimer’s disease, systematic review and systematic review with meta-analysis terms were used to abstract data from included studies. Main Findings: 11 SRs and SRs with meta-analysis were reviewed which revealed positive effect of music therapy on five major outcomes with 9 studies effect on behavioral outcome, 6 studies with positive effect on psychosocial outcome reducing anxiety, 6 with improved cognition, 1 study revealed with improved quality of life and 1 study revealed effect on physiological outcomes. Conclusion: Music therapy has positive effect on treatment of dementia but further studies with larger sample size and specified to single intervention should be conducted to provide generalisable and precise results on this topic.展开更多
Objective:To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression(PSD).Methods:A total of 100 patients with PSD who met the inclusion criteria w...Objective:To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression(PSD).Methods:A total of 100 patients with PSD who met the inclusion criteria were randomly divided into an experimental group(50 cases)and a control group(50 cases)using the random number table method,and the enrollment was in order of admission time.The control group used conventional treatment of oral antidepressant Deanxit tablets(0.5 mg flupenthixol+10 mg melitracen)with the dose appropriately adjusted according to the patient’s medication effect,and modern rehabilitation treatment given selectively according to the patient’s condition.The experimental group had similar treatment as the control group with the addition of traditional Chinese medicine(TCM)acupuncture combined with emotional intervention.The application effects of both groups before and after treatment were verified using the Hamilton Depression Rating Scale(Ham-D),National Institutes of Health Stroke Scale(NIHSS),and Activities of Daily Living(ADL),serotonin levels were measured,and statistical analyses were carried out.Results:The total effective rate of patients in the experimental group was significantly higher than that in the control group,and the Ham-D score,NIHSS score,ADL score,and serotonin level after treatment were significantly higher than those in the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:For patients with PSD,adding TCM acupuncture with emotional intervention on top of conventional treatment significantly improve the clinical efficacy and better improve the daily life ability of patients.展开更多
BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subcortical form of dementia characterized by memory deficits and psychomotor slowing.However,HAD often presents with symptoms similar to those...BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subcortical form of dementia characterized by memory deficits and psychomotor slowing.However,HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease(CJD),particularly in patients with acquired immune deficiency syndrome(AIDS).CASE SUMMARY We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure.The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins.His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern.Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination.Initially,symptomatic treatment and administration of amantadine were pursued for presumed CJD,but the patient’s condition continued to deteriorate.By contrast,the patient’s condition improved following anti-HIV therapy.This individual is also the only patient with this prognosis to have survived over 4 years.Thus,the diagnosis was revised to HAD.CONCLUSION In the diagnostic process of rapidly progressive dementia,it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty.The 14-3-3 protein should not be regarded as the definitive marker for CJD.Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision,especially in AIDS patients with potential CJD.Ultimately,a trial of diagnostic treatment may be considered when additional testing is not feasible.展开更多
BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other dise...BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.展开更多
Globally there is an increased digitalization going on with an increasing number of people having access to the internet, having smartphones and now also in many countries being expected to access health-related infor...Globally there is an increased digitalization going on with an increasing number of people having access to the internet, having smartphones and now also in many countries being expected to access health-related information and schedule appointments through websites, apps or web-based portals. Healthcare providers have also adopted this with an increasing number of public or private organizations providing web-based portals as well as app interfaces to some of the largest electronic healthcare systems. The benefit of this is easier access, more efficient provision of services, increased transparency and improved workflows. This may increase the population’s capability to manage their conditions and reduce the contacts to, thereby burdening healthcare professionals. But not all will be able to benefit from this digital (r)evolution. Those who will not be able to include people with dementia. For people with dementia to also be able to take advantage of digital health tools and services, it will require planning and involvement of caregivers. In 2017, we presented the Epital Care Model as a framework to organize an efficient people-centered cross-disciplinary and cross-sectoral way to organize activities, roles, responsibilities and describe geographical locations and used technologies in response to individuals’ specific diagnoses and everyday changes in their condition. In 2021, an EU-funded project was initiated to investigate how living labs and scaling up could be done building upon the ECM. One of the living labs was organized around an organization providing care to PWD in Netherlands. In the period 2021 to 2024, we have tried to identify ways for how the ECM could be used to digitally enable the services provided by the organization. In 2022, the care organization tanteLouise started a project originally named Daycare Centre2.0 (now called “Van Thuis Uit” meaning “From Home”), together with healthcare insurance company CZ, and developed a model for onboarding people with dementia and introducing them to specific interventions based on their personal goals and needs. We here present how the ECM and the “Van Thuis Uit” can be mapped within each other to create synergy in creating a healthcare setting for people with dementia. This work may serve as a model for other conditions, where individuals are likely to need more intensive support from their informal caregivers due to a relatively rapid progression of the condition or development of severe impairments. Examples here can be neurologic conditions such as multiple sclerosis and amyotrophic lateral sclerosis or the final stage of conditions that require palliation.展开更多
Alzheimer’s disease (AD) and associated dementia patient numbers continue to increase globally with associated economic costs to healthcare systems. Of note is the increase in numbers in lower and middle-income count...Alzheimer’s disease (AD) and associated dementia patient numbers continue to increase globally with associated economic costs to healthcare systems. Of note is the increase in numbers in lower and middle-income countries (LMICs) including Sub-Saharan African (SSA) countries, which already face challenges with their health budgets from communicable and non-communicable diseases. Ghana, an SSA country, faces the problem of healthcare budgetary difficulties and the additional impact of AD as a consequence of increasing population strata of old aged persons (OAPs) due to the demographic transition effect. This article uses examples of known patients’ illness courses to give a perspective on the lived experience of patients with dementia (PWD) in Ghana, living amongst a populace with a culture of stigmatization of PWD, and a relatively fragile public mental health system (PMHS) for those with mental illness, including AD. The lived experience of AD patients is characterised by stigmatisation, discrimination, non-inclusiveness, diminished dignity and human rights abuses in the face of their mental disability, and eventually death. This article is an advocacy article giving voice to the voiceless and all persons suffering from AD and other dementias in Ghana, whilst pleading for a call to action from healthcare professionals and responsible state agencies.展开更多
Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment o...Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.展开更多
Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine predic...Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To asses...BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.展开更多
This study used Arksey and O’Malley’s scoping review methodology as a framework and searched the following databases:PubMed,Embase,EBSCO,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang,VIP,and the Chinese...This study used Arksey and O’Malley’s scoping review methodology as a framework and searched the following databases:PubMed,Embase,EBSCO,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang,VIP,and the Chinese Biomedical Literature Database.The database is open to December 20,2023,and documents related to the fear of dementia among the elderly in the community are described and analyzed to provide a reference for future research in this field.At the same time,we screened,extracted,and summarized relevant information from 21 included documents(16 in English and 5 in Chinese),which consisted of 16 cross-sectional studies,2 quasi-experimental studies,2 randomized controlled studies,and 1 longitudinal study.Sixteen of the included documents mentioned the incidence or level of dementia fear among the elderly in the community,2 addressed the adverse effects of dementia fear,and 4 reported prevention and intervention measures for dementia fear.In total,there are 8 assessment tools,and the influencing factors are categorized into sociodemographic characteristics,psychological and behavioral characteristics,sociocultural background factors,and health and dementia-related factors.The final conclusion is that the fear of dementia is common among the elderly in the community.In the future,the application of research tools should be expanded among middle-aged individuals,with considerations for other types of dementia in mind.It is recommended to conduct large-scale,multi-center randomized controlled trials while confirming the intervention’s effect on different types of middle-aged and elderly individuals,focusing on the long-term impact of these intervention measures to promote healthy aging.展开更多
Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the...Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to March 2022 were selected as the study subjects.The patients were divided into two groups based on different treatment methods:the control group(treated with memantine hydrochloride,34 cases)and the treatment group(treated with sodium oligomannate+memantine hydrochloride,34 cases).Cognitive function,activities of daily living,neurotransmitters,serum intestinal flora metabolic markers,inflammatory factors,neurotrophic factors,and adverse reactions were compared between the two groups.Results:The treatment group showed better cognitive function,quality of life scores,and levels of relevant metabolic markers in the body compared to the control group,with statistically significant differences(P<0.05).The incidence of adverse reactions between the two groups(treatment group:2%;control group:4%)was not statistically significant(χ^(2)=0.731,P=0.393).Conclusion:Sodium oligomannate combined with memantine hydrochloride has better efficacy than the control group for treating senile Alzheimer’s dementia.It significantly improves and restores cognitive function and daily living abilities,benefits neurotransmitter secretion and internal regulation,upregulates the expression of neurotrophic factors,and has fewer adverse reactions,making it a treatment worthy of further clinical promotion and application.展开更多
基金Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University,No.JYHL2019FMS25and The Key Research and Development Program of Jining,No.2022YXNS028.
文摘BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease.Long-term seizures can seriously affect the prognosis and quality of life of patients.Electroencephalogram(EEG)is the simplest way to diagnose epilepsy,and plays an important role in predicting seizures and guiding medication.AIM To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform discharges.METHODS From January 2017 to June 2020,10 patients with post-stroke epilepsy in our hospital were included.The clinical,imaging,and EEG characteristics were collected.The stroke location,seizure type,and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively analyzed.RESULTS In all 10 patients,epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage;these manifested as sharp wave,sharp-wave complex,or spike discharges in the anterior head lead of the side opposite to the lesion.CONCLUSION In EEG,epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.
基金the National Key R&D Program of China(Grant No.2019YFC1709900)National Natural Science Foundation of China(Grant No.71804022)+1 种基金Natural Science Foundation of Henan province(Grant No.232300420256)Medical technologies R&D Program of Henan province(Grant No.LHGJ20220348).
文摘Background:To investigate the effects of acupuncture on post-stroke limb spasm model rats and the underlying mechanism.Methods:A total of 50 Sprague-Dawley rats were randomly divided into three groups,Control group(10),Model group(20)and Zhishen Tiaoxing(ZSTX)acupuncture group(20).Middle cerebral artery occlusion was conducted in SD rats to establish post-stroke limb spasm rats,which were treated with ZSTX acupuncture.Behavioral assays were determined by the Narrow ally test,the limb muscle tension was detected by the BL-420S test system,and infarct volume was assessed after the cerebral infarction by 2,3,5-triphenyltetrazolium chloride staining.Heterogeneous neurotransmitterγ-aminobutyric acid(GABA)and its receptors GABAA and GABAB in the cerebral cortex of the infarct area were determined by immunofluorescence assay.The release of Trkb and K-Cl cotransporter isoform 2 was detected by an immunofluorescence double labeling study.Western Blot was utilized to measure the expression of BDNF and Trkb.Results:The results showed that the behavioral assays in post-stroke limb spasm rats were significantly improved by the treatment of ZSTX acupuncture.14 days of ZSTX acupuncture can effectively inhibit muscle tone and decrease Infarct volume,which was measured with BL-420S biological function experiment system and triphenyltetrazolium chloride.Meanwhile,the results of Double-Label Immunofluorescence Assays showed that ZSTX acupuncture improved the expression of GABA,GABAA,GABAB,BDNF,and K-Cl cotransporter isoform 2.Double-Label Immunofluorescence Assays and WB results showed that 14 days ZSTX acupuncture declined the expression of Trkb.Conclusions:Our results suggest that 14 days of ZSTX acupuncture can significantly improve post-stroke limb spasm.Meanwhile,the pathogenesis of post-stroke limb spasm and the efficacy of ZSTX acupuncture involve metabolic pathways of neurotransmitters,and electro-acupuncture can treat post-stroke limb spasm by regulating BDNF/Trkb-KCC2 signaling pathway.
文摘BACKGROUND Post-stroke depression(PSD)is a common and debilitating condition affecting stroke survivors,significantly impacting their recovery and overall quality of life.AIM To assess the effects of early PSD screening on functional outcomes,quality of life,and mortality.METHODS From an initial pool of 1065 articles,6 studies met the inclusion criteria and were selected for analysis.Functional outcomes were measured using the functional independence measure(FIM).RESULTS The analysis revealed a significant improvement in FIM scores for a PSD scree-ning group compared to controls[standardized mean difference(SMD)=8.90,95%confidence interval(CI):4.65-13.15,P<0.01].Quality of life was assessed using the Stroke-Specific Quality of Life Scale,with the screening group showing significantly higher scores(SMD=20.83,95%CI:15.27-26.38,P<0.01).Mortality analysis indicated a reduction in five-year mortality rates for the PSD screening group.CONCLUSION Early PSD screening enhances functional recovery,improves quality of life,and reduces mortality rates in stroke survivors.Thus,integrating PSD screening into routine stroke care improves long-term outcomes for patients.
基金Supported by the Joint Guidance Project of Qiqihar Science and Technology Plan in 2020,No.LHYD-202054。
文摘BACKGROUND Stroke has become one of the most serious life-threatening diseases due to its high morbidity,disability,recurrence and mortality rates.AIM To explore the intervention effect of multi-disciplinary treatment(MDT)extended nursing model on negative emotions and quality of life of young patients with post-stroke.METHODS A total of 60 young stroke patients who were hospitalized in the neurology department of our hospital from January 2020 to December 2021 were selected and randomly divided into a control group and an experimental group,with 30 patients in each group.The control group used the conventional care model and the experimental group used the MDT extended nursing model.After the inhospital and 3-mo post-discharge interventions,the differences in negative emotions and quality of life scores between the two groups were evaluated and analyzed at the time of admission,at the time of discharge and after discharge,respectively.RESULTS There are no statistically significant differences in the negative emotions scores between the two groups at admission,while there are statistically significant differences in the negative emotions scores within each group at admission and discharge,at discharge and post-discharge,and at discharge and post-discharge.In addition,the negative emotions scores were all statistically significant at discharge and after discharge when compared between the two groups.There was no statistically significant difference in quality of life scores at the time of admission between the two groups,and the difference between quality of life scores at the time of admission and discharge,at the time of discharge and post-discharge,and at the time of admission and post-discharge for each group of patients was statistically significant.CONCLUSION The MDT extended nursing mode can improve the negative emotion of patients and improve their quality of life.Therefore,it can be applied in future clinical practice and is worthy of promotion.
基金the National Natural Science Foundation of China(No.31800851)Natural Science Foundation of Hubei Province(No.2022CFB456)The Research Fund of Jianghan University(No.08210011).
文摘Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
文摘In this commentary,we summarize some of the key points of the original paper“Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality,complications,or outcomes”and offer support for the proposed results.Specifically,we address how early percutaneous endoscopic gastrostomy(PEG)tube placement may reduce hospital length of stay and costs.We also discuss topics related to the article including PEG weaning and post-stroke nutritional formulation.However,we note that concerns purported by previous studies that early PEG placement may worsen outcomes are not fully addressed,and further research is needed.
基金supported by Guangdong Medical Science Foundation(Grant No.A2020370A2021199)Guangdong Administration of Traditional Chinese Medicine Project(Grant No.20211328).
文摘In this work,we intended to connect clinimetrics with holism in traditional Chinese medicine towards multidimensional assessment of post-stroke sequelae in real-world setting,as a bridge between inheritance and innovation.Firstly,a systematic search of current evidence that supported integrated treatment of traditional Chinese and Western medicine for post-stroke sequelae sufferers was performed.Secondly,on the basis of available evidence,we presented couples of implications.Lastly,as psychosomatic perspective is one of the main academic paradigms of traditional Chinese medicine holism,we chiefly proposed comprehensive assessment for both motor and non-motor severities to probably match consonance with traditional Chinese medicine practice that treats psycho-/somatic-complains simultaneously.
文摘Background: Dementia is a condition with progressive cognitive dysfunction and manifestation of both behavioral and psychosocial symptoms. Non-pharmacological measures such as music therapy are gaining importance since efficacy and safety of people with dementia have been questionable for pharmacological measures. Patient’s response to music is persistent even in the later stage of dementia. Aim: This rapid review aims to identify, analyze, evaluate, and summarize the best available evidence on the effectiveness of music-based therapeutic interventions among people with dementia. Method: CINAHL Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened the literature search results. Effectiveness, music-based therapeutic intervention, dementia, Alzheimer’s disease, systematic review and systematic review with meta-analysis terms were used to abstract data from included studies. Main Findings: 11 SRs and SRs with meta-analysis were reviewed which revealed positive effect of music therapy on five major outcomes with 9 studies effect on behavioral outcome, 6 studies with positive effect on psychosocial outcome reducing anxiety, 6 with improved cognition, 1 study revealed with improved quality of life and 1 study revealed effect on physiological outcomes. Conclusion: Music therapy has positive effect on treatment of dementia but further studies with larger sample size and specified to single intervention should be conducted to provide generalisable and precise results on this topic.
基金The Shandong Traditional Chinese Medicine Science and Technology Development Program 2020Q132。
文摘Objective:To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression(PSD).Methods:A total of 100 patients with PSD who met the inclusion criteria were randomly divided into an experimental group(50 cases)and a control group(50 cases)using the random number table method,and the enrollment was in order of admission time.The control group used conventional treatment of oral antidepressant Deanxit tablets(0.5 mg flupenthixol+10 mg melitracen)with the dose appropriately adjusted according to the patient’s medication effect,and modern rehabilitation treatment given selectively according to the patient’s condition.The experimental group had similar treatment as the control group with the addition of traditional Chinese medicine(TCM)acupuncture combined with emotional intervention.The application effects of both groups before and after treatment were verified using the Hamilton Depression Rating Scale(Ham-D),National Institutes of Health Stroke Scale(NIHSS),and Activities of Daily Living(ADL),serotonin levels were measured,and statistical analyses were carried out.Results:The total effective rate of patients in the experimental group was significantly higher than that in the control group,and the Ham-D score,NIHSS score,ADL score,and serotonin level after treatment were significantly higher than those in the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:For patients with PSD,adding TCM acupuncture with emotional intervention on top of conventional treatment significantly improve the clinical efficacy and better improve the daily life ability of patients.
文摘BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subcortical form of dementia characterized by memory deficits and psychomotor slowing.However,HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease(CJD),particularly in patients with acquired immune deficiency syndrome(AIDS).CASE SUMMARY We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure.The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins.His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern.Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination.Initially,symptomatic treatment and administration of amantadine were pursued for presumed CJD,but the patient’s condition continued to deteriorate.By contrast,the patient’s condition improved following anti-HIV therapy.This individual is also the only patient with this prognosis to have survived over 4 years.Thus,the diagnosis was revised to HAD.CONCLUSION In the diagnostic process of rapidly progressive dementia,it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty.The 14-3-3 protein should not be regarded as the definitive marker for CJD.Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision,especially in AIDS patients with potential CJD.Ultimately,a trial of diagnostic treatment may be considered when additional testing is not feasible.
基金Supported by Science and Technology Planning Project of Zhanjiang,No.2021A05071Clinic and Basic Research Project of Guangdong Medical University,No.4SG23284GThe Affiliated Hospital of Guangdong Medical University,No.LCYJ2018A003.
文摘BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.
文摘Globally there is an increased digitalization going on with an increasing number of people having access to the internet, having smartphones and now also in many countries being expected to access health-related information and schedule appointments through websites, apps or web-based portals. Healthcare providers have also adopted this with an increasing number of public or private organizations providing web-based portals as well as app interfaces to some of the largest electronic healthcare systems. The benefit of this is easier access, more efficient provision of services, increased transparency and improved workflows. This may increase the population’s capability to manage their conditions and reduce the contacts to, thereby burdening healthcare professionals. But not all will be able to benefit from this digital (r)evolution. Those who will not be able to include people with dementia. For people with dementia to also be able to take advantage of digital health tools and services, it will require planning and involvement of caregivers. In 2017, we presented the Epital Care Model as a framework to organize an efficient people-centered cross-disciplinary and cross-sectoral way to organize activities, roles, responsibilities and describe geographical locations and used technologies in response to individuals’ specific diagnoses and everyday changes in their condition. In 2021, an EU-funded project was initiated to investigate how living labs and scaling up could be done building upon the ECM. One of the living labs was organized around an organization providing care to PWD in Netherlands. In the period 2021 to 2024, we have tried to identify ways for how the ECM could be used to digitally enable the services provided by the organization. In 2022, the care organization tanteLouise started a project originally named Daycare Centre2.0 (now called “Van Thuis Uit” meaning “From Home”), together with healthcare insurance company CZ, and developed a model for onboarding people with dementia and introducing them to specific interventions based on their personal goals and needs. We here present how the ECM and the “Van Thuis Uit” can be mapped within each other to create synergy in creating a healthcare setting for people with dementia. This work may serve as a model for other conditions, where individuals are likely to need more intensive support from their informal caregivers due to a relatively rapid progression of the condition or development of severe impairments. Examples here can be neurologic conditions such as multiple sclerosis and amyotrophic lateral sclerosis or the final stage of conditions that require palliation.
文摘Alzheimer’s disease (AD) and associated dementia patient numbers continue to increase globally with associated economic costs to healthcare systems. Of note is the increase in numbers in lower and middle-income countries (LMICs) including Sub-Saharan African (SSA) countries, which already face challenges with their health budgets from communicable and non-communicable diseases. Ghana, an SSA country, faces the problem of healthcare budgetary difficulties and the additional impact of AD as a consequence of increasing population strata of old aged persons (OAPs) due to the demographic transition effect. This article uses examples of known patients’ illness courses to give a perspective on the lived experience of patients with dementia (PWD) in Ghana, living amongst a populace with a culture of stigmatization of PWD, and a relatively fragile public mental health system (PMHS) for those with mental illness, including AD. The lived experience of AD patients is characterised by stigmatisation, discrimination, non-inclusiveness, diminished dignity and human rights abuses in the face of their mental disability, and eventually death. This article is an advocacy article giving voice to the voiceless and all persons suffering from AD and other dementias in Ghana, whilst pleading for a call to action from healthcare professionals and responsible state agencies.
基金Supported by National Natural Science Foundation of China (General Program),No.32060182Qiannan Prefecture Science and Technology Plan Project in China,No.Qiannan Kehe She Zi[2022]No.1.
文摘Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.
文摘Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
文摘BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.
文摘This study used Arksey and O’Malley’s scoping review methodology as a framework and searched the following databases:PubMed,Embase,EBSCO,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang,VIP,and the Chinese Biomedical Literature Database.The database is open to December 20,2023,and documents related to the fear of dementia among the elderly in the community are described and analyzed to provide a reference for future research in this field.At the same time,we screened,extracted,and summarized relevant information from 21 included documents(16 in English and 5 in Chinese),which consisted of 16 cross-sectional studies,2 quasi-experimental studies,2 randomized controlled studies,and 1 longitudinal study.Sixteen of the included documents mentioned the incidence or level of dementia fear among the elderly in the community,2 addressed the adverse effects of dementia fear,and 4 reported prevention and intervention measures for dementia fear.In total,there are 8 assessment tools,and the influencing factors are categorized into sociodemographic characteristics,psychological and behavioral characteristics,sociocultural background factors,and health and dementia-related factors.The final conclusion is that the fear of dementia is common among the elderly in the community.In the future,the application of research tools should be expanded among middle-aged individuals,with considerations for other types of dementia in mind.It is recommended to conduct large-scale,multi-center randomized controlled trials while confirming the intervention’s effect on different types of middle-aged and elderly individuals,focusing on the long-term impact of these intervention measures to promote healthy aging.
基金Clinical Special Project of Fujian University of Traditional Chinese Medicine(Project Number:XB2023027)。
文摘Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to March 2022 were selected as the study subjects.The patients were divided into two groups based on different treatment methods:the control group(treated with memantine hydrochloride,34 cases)and the treatment group(treated with sodium oligomannate+memantine hydrochloride,34 cases).Cognitive function,activities of daily living,neurotransmitters,serum intestinal flora metabolic markers,inflammatory factors,neurotrophic factors,and adverse reactions were compared between the two groups.Results:The treatment group showed better cognitive function,quality of life scores,and levels of relevant metabolic markers in the body compared to the control group,with statistically significant differences(P<0.05).The incidence of adverse reactions between the two groups(treatment group:2%;control group:4%)was not statistically significant(χ^(2)=0.731,P=0.393).Conclusion:Sodium oligomannate combined with memantine hydrochloride has better efficacy than the control group for treating senile Alzheimer’s dementia.It significantly improves and restores cognitive function and daily living abilities,benefits neurotransmitter secretion and internal regulation,upregulates the expression of neurotrophic factors,and has fewer adverse reactions,making it a treatment worthy of further clinical promotion and application.
