Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on id...Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on identifying its active ingredients and their target proteins.Methods:The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe.It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database.These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe’s core active ingredients.In vitro cell experiments were conducted on hypoxic HT22 cells,involving CCK8 assay,lentiviral transfection to silence autophagy related 9B(ATG9B),immunofluorescence staining,and qPCR validation to investigate the effects of the recipe on autophagy.Results:The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network.Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs.Molecular docking showed quercetin,kaempferol,myrcene,and conferone as key ingredients targeting autophagy-related proteins.Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions,reduced apoptosis,and modulated the expression of autophagy-related factors,thereby decreasing apoptosis rates in HT22 cells.Conclusion:The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins.Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions,though further research is needed to fully understand its mechanisms and clinical applications.展开更多
Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascul...Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.展开更多
Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cogniti...Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients(29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits(odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall(odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.展开更多
Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns...Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China(approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.展开更多
Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cogn...Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.展开更多
Background: The Geriatric Depression Scale (GDS) is widely used to assess depressive symptoms in clinical and research settings. This study utilized a 4 factor solution for the 30-item GDS to explore differences in th...Background: The Geriatric Depression Scale (GDS) is widely used to assess depressive symptoms in clinical and research settings. This study utilized a 4 factor solution for the 30-item GDS to explore differences in the presentation of depressive symptoms in various types of cognitive impairment. Method: Retrospective chart review was conducted on 254 consecutive cases of community dwelling elderly newly diagnosed with mild Alzheimer’s Dementia (AD) n = 122, mild Vascular Dementia (VaD) n = 71 or Amnestic Mild Cognitive Impairment (aMCI) n = 32 and Non-Amnestic MCI (nMCI) n = 29. Results: Analysis revealed no significant differences (p 05). No statistically significant differences were found between VaD and nMCI or between the MCI groups. Conclusions: Support is provided for the use of GDS subscales in a wide range of cognitively impaired elderly. This study suggests in mild dementia the number and type of depressive symptoms vary significantly between AD and VaD. There are indications that aMCI patients are similar in their symptom endorsement to AD and nMCI are similar to VaD which is consistent with some of the notions regarding likely trajectories of the respective MCI groups.展开更多
As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementi...As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementia VCI.Early symptoms of non-dementia VCI are hidden and difficult to identify.About 50% of patients develop dementia.This article reviews the correlation between WMLs and VCI in terms of etiology,risk factors,pathogenesis and imaging manifestations.It provides scientific basis or ideas for clinical diagnosis and treatment for WMLs and VCI.展开更多
The prescription of Tianma Xingnao Capsule is composed of Gastrodiae Rhizoma,Pheretima,Acori Tatarinowii Rhizoma,Polygalae Radix,Rehmanniae Radix Praeparata,and Cistanches Herba.It has effects of nourishing liver and ...The prescription of Tianma Xingnao Capsule is composed of Gastrodiae Rhizoma,Pheretima,Acori Tatarinowii Rhizoma,Polygalae Radix,Rehmanniae Radix Praeparata,and Cistanches Herba.It has effects of nourishing liver and kidney,dredging collaterals and relieving pain.More than 20 years of clinical application and evidence-based medical research have shown that Tianma Xingnao Capsule has a significant therapeutic effect on vascular cognitive impairment and neuropathic headache.In order to further guide the proper clinical use of this prescription,the consensus expert group conducted a comprehensive analysis of the prescription of Tianma Xingnao Capsule.Combining the existing evidence-based medicine evidence and the experience of clinical experts,this consensus report standardized the usage,dosage,duration and safety of Tianma Xingnao Capsule in the treatment of vascular cognitive impairment and neuropathic headache.It is expected to provide a theoretical basis for clinically reasonable and safe use of Tianma Xingnao Capsule.展开更多
The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids ...The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories. Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model. The fitting curves for each factor were obtained using Matlab software. Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors. Our results demonstrated that vascular cognitive impairment involves multiple factors. These factors include excitatory amino acid toxicity and nitric oxide toxicity. These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.展开更多
BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown t...BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P 〈 0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P 〈 0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group (P 〈 0.01). Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION: Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.展开更多
Objective: To investigate functional connectivity within default mode network (DMN) and ex-ecutive control network (ECN) in vascular cognitive im-pairment, no dementia (VCIND). Methods: Twenty-eight VCIND pati...Objective: To investigate functional connectivity within default mode network (DMN) and ex-ecutive control network (ECN) in vascular cognitive im-pairment, no dementia (VCIND). Methods: Twenty-eight VCIND patients and sixteen healthy controls were recruit-ed. A seed-based connectivity analysis was performed us-ing data from resting-state functional magnetic resonance imaging (fMRI). Based on previous fndings, posteriorcingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) were chosen as regions of interest to study these networks.One-sample t-test and two-sample t-test were used for statistical analysis. Results: Compared with thecontrols, the VCIND group exhibited increased functional activity in such DMN regions as the left inferior temporal gyrus, parahippocampal gyrus, and medial frontal gyrus. The VCIND group had decreased functional connectivity of DMN at right superior frontal gyrus, left mid-cingu-late area, the medial part of left superior frontal gyrus, and bilateral medial frontal gyrus. The VCIND group also showed decreased functional connectivity of ECN pri-marilyat left inferior parietal gyrus, right angular gyrus, right middle occipital gyrus, and right middle frontal cor-tex. Conclusions: Increased functional connectivity with-in DMN and decreased functional connectivity within ECN suggested dysfunction of these two networks, which mightbe associated with the cognitive defcitsin patients with VCIND. These fndingsmay help usunderstandthe pathogenesis and clinical characteristics of VCIND.展开更多
Vascular mild cognitive impairment(VaMCI)represents the early stage of symptoms of vascular cognitive impairment(VCI).There are many intervention factors in this period.If the active treatment can delay the further de...Vascular mild cognitive impairment(VaMCI)represents the early stage of symptoms of vascular cognitive impairment(VCI).There are many intervention factors in this period.If the active treatment can delay the further development of the disease and even reduce the risk of transforming into vascular dementia(VaD).As a widely used imaging method,multi-mode magnetic resonance imaging can evaluate the brain structure and function of patients with VaMCI noninvasively and explore the relationship between brain structure,function and cognitive function change.It is beneficial to provide an idea for early diagnosis of VaMCI and to further understand the neuropathologic mechanism of its occurrence,which has broad application prospects.In this paper,the research status and new methods of VaMCI are reviewed by using multi-mode magnetic resonance imaging in recent years.展开更多
As the population ages,the number of patients with vascular cognitive impairment(VCI)increases,which increases the burden on patient's family and social.At present,the treatment and pathogenesis of VCI is still un...As the population ages,the number of patients with vascular cognitive impairment(VCI)increases,which increases the burden on patient's family and social.At present,the treatment and pathogenesis of VCI is still unclear.This paper reviews the literature on VCI pathogenesis,especially the molecular mechanism(oxidative stress,endoplasmic reticulum stress,inflammation,autophagy.),aiming to provide direction and reference for VCI pathogenesis research and target therapy.展开更多
It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatm...It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatment(25 cases of mild cognitive dysfunction,25 cases of moderate cognitive dysfunction)were divided into two groups,where a medical drug treatment group and a control group established with 25 cases in each group.The cognitive function of each group of patients was evaluated before operation,7 days after operation,30 days after operation,and 180 days after operation.CTP was used to compare the hemodynamic changes in patients before and after operation.The severe stenosis or occlusion of the middle cerebral artery in patients can be improved,and the intracranial blood supply of patients with poorly compensated medial cranial circulation and hypoperfusion can be restored to a certain extent.Meanwhile,improvement of cognitive function was definitive in some patients with cognitive dysfunction.To guide the formulation of treatment plans for patients with severe middle cerebral artery stenosis or occlusion.展开更多
Summary: This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for t...Summary: This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=-0.037 and P=0.000; P=0.023 and P=-0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.展开更多
<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevent...<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. <strong>Methods:</strong> To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. <strong>Results:</strong> There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76);2.98 (2.58, 3.45);2.79 (1.69, 4.59);2.35 (1.93, 2.85);2.25 (1.86, 2.71);2.14 (2.10, 2.18);1.82 (1.62, 2.03);1.54 (1.24, 1.92);1.45 (1.34, 1.56);0.83 (0.78, 0.89). <strong>Conclusion: </strong>Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.展开更多
文摘Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on identifying its active ingredients and their target proteins.Methods:The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe.It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database.These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe’s core active ingredients.In vitro cell experiments were conducted on hypoxic HT22 cells,involving CCK8 assay,lentiviral transfection to silence autophagy related 9B(ATG9B),immunofluorescence staining,and qPCR validation to investigate the effects of the recipe on autophagy.Results:The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network.Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs.Molecular docking showed quercetin,kaempferol,myrcene,and conferone as key ingredients targeting autophagy-related proteins.Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions,reduced apoptosis,and modulated the expression of autophagy-related factors,thereby decreasing apoptosis rates in HT22 cells.Conclusion:The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins.Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions,though further research is needed to fully understand its mechanisms and clinical applications.
基金supported by the Natural Science Foundation of Liaoning Province of China,No.20170541036(to HYL)
文摘Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2015160)
文摘Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients(29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits(odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall(odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.
基金supported by the National Natural Science Foundation of China,No.81771237(to YXG)the National Key Basic Research Program of China(973 Program),No.2014CB541604(to YXG)+1 种基金the "Shu Guang" Project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation,China,No.16SG02(to LC)the Scientific Research Project of Huashan Hospital of Fudan University of China,No.2016QD082(to YL)
文摘Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China(approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.
文摘Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.
文摘Background: The Geriatric Depression Scale (GDS) is widely used to assess depressive symptoms in clinical and research settings. This study utilized a 4 factor solution for the 30-item GDS to explore differences in the presentation of depressive symptoms in various types of cognitive impairment. Method: Retrospective chart review was conducted on 254 consecutive cases of community dwelling elderly newly diagnosed with mild Alzheimer’s Dementia (AD) n = 122, mild Vascular Dementia (VaD) n = 71 or Amnestic Mild Cognitive Impairment (aMCI) n = 32 and Non-Amnestic MCI (nMCI) n = 29. Results: Analysis revealed no significant differences (p 05). No statistically significant differences were found between VaD and nMCI or between the MCI groups. Conclusions: Support is provided for the use of GDS subscales in a wide range of cognitively impaired elderly. This study suggests in mild dementia the number and type of depressive symptoms vary significantly between AD and VaD. There are indications that aMCI patients are similar in their symptom endorsement to AD and nMCI are similar to VaD which is consistent with some of the notions regarding likely trajectories of the respective MCI groups.
文摘As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementia VCI.Early symptoms of non-dementia VCI are hidden and difficult to identify.About 50% of patients develop dementia.This article reviews the correlation between WMLs and VCI in terms of etiology,risk factors,pathogenesis and imaging manifestations.It provides scientific basis or ideas for clinical diagnosis and treatment for WMLs and VCI.
基金Funding from Yunnan Chinese Medicine Clinical Key Discipline,Yunnan University of Traditional Chinese Medicine Encephalopathy School Construction Project(30372103700).
文摘The prescription of Tianma Xingnao Capsule is composed of Gastrodiae Rhizoma,Pheretima,Acori Tatarinowii Rhizoma,Polygalae Radix,Rehmanniae Radix Praeparata,and Cistanches Herba.It has effects of nourishing liver and kidney,dredging collaterals and relieving pain.More than 20 years of clinical application and evidence-based medical research have shown that Tianma Xingnao Capsule has a significant therapeutic effect on vascular cognitive impairment and neuropathic headache.In order to further guide the proper clinical use of this prescription,the consensus expert group conducted a comprehensive analysis of the prescription of Tianma Xingnao Capsule.Combining the existing evidence-based medicine evidence and the experience of clinical experts,this consensus report standardized the usage,dosage,duration and safety of Tianma Xingnao Capsule in the treatment of vascular cognitive impairment and neuropathic headache.It is expected to provide a theoretical basis for clinically reasonable and safe use of Tianma Xingnao Capsule.
基金supported by the Natural Science Foundation of Heilongjiang Province,No.D200916a grant from Youth Science Foundation of Heilongjiang Province,No.QC2009C65
文摘The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories. Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model. The fitting curves for each factor were obtained using Matlab software. Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors. Our results demonstrated that vascular cognitive impairment involves multiple factors. These factors include excitatory amino acid toxicity and nitric oxide toxicity. These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.
文摘BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P 〈 0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P 〈 0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group (P 〈 0.01). Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION: Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.
文摘Objective: To investigate functional connectivity within default mode network (DMN) and ex-ecutive control network (ECN) in vascular cognitive im-pairment, no dementia (VCIND). Methods: Twenty-eight VCIND patients and sixteen healthy controls were recruit-ed. A seed-based connectivity analysis was performed us-ing data from resting-state functional magnetic resonance imaging (fMRI). Based on previous fndings, posteriorcingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) were chosen as regions of interest to study these networks.One-sample t-test and two-sample t-test were used for statistical analysis. Results: Compared with thecontrols, the VCIND group exhibited increased functional activity in such DMN regions as the left inferior temporal gyrus, parahippocampal gyrus, and medial frontal gyrus. The VCIND group had decreased functional connectivity of DMN at right superior frontal gyrus, left mid-cingu-late area, the medial part of left superior frontal gyrus, and bilateral medial frontal gyrus. The VCIND group also showed decreased functional connectivity of ECN pri-marilyat left inferior parietal gyrus, right angular gyrus, right middle occipital gyrus, and right middle frontal cor-tex. Conclusions: Increased functional connectivity with-in DMN and decreased functional connectivity within ECN suggested dysfunction of these two networks, which mightbe associated with the cognitive defcitsin patients with VCIND. These fndingsmay help usunderstandthe pathogenesis and clinical characteristics of VCIND.
基金Projects Funded by Scientific and Technological Activities of Overseas Students in Shanxi Province in 2018,Project No:Jincaishe[2018]No.123Shanxi Province's Key Research and Development Projects in Social Development.Project No:201803D31129.
文摘Vascular mild cognitive impairment(VaMCI)represents the early stage of symptoms of vascular cognitive impairment(VCI).There are many intervention factors in this period.If the active treatment can delay the further development of the disease and even reduce the risk of transforming into vascular dementia(VaD).As a widely used imaging method,multi-mode magnetic resonance imaging can evaluate the brain structure and function of patients with VaMCI noninvasively and explore the relationship between brain structure,function and cognitive function change.It is beneficial to provide an idea for early diagnosis of VaMCI and to further understand the neuropathologic mechanism of its occurrence,which has broad application prospects.In this paper,the research status and new methods of VaMCI are reviewed by using multi-mode magnetic resonance imaging in recent years.
基金supported by Inner Mongolia Natural Science Foundation(Grant No:2021MS08169).
文摘As the population ages,the number of patients with vascular cognitive impairment(VCI)increases,which increases the burden on patient's family and social.At present,the treatment and pathogenesis of VCI is still unclear.This paper reviews the literature on VCI pathogenesis,especially the molecular mechanism(oxidative stress,endoplasmic reticulum stress,inflammation,autophagy.),aiming to provide direction and reference for VCI pathogenesis research and target therapy.
基金Clinical Study of Endovascular Treatment of Severe Middle Cerebral Artery Stenosis or Occlusion and Vascular Cognitive Impairment.Project No.:2019zc184。
文摘It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatment(25 cases of mild cognitive dysfunction,25 cases of moderate cognitive dysfunction)were divided into two groups,where a medical drug treatment group and a control group established with 25 cases in each group.The cognitive function of each group of patients was evaluated before operation,7 days after operation,30 days after operation,and 180 days after operation.CTP was used to compare the hemodynamic changes in patients before and after operation.The severe stenosis or occlusion of the middle cerebral artery in patients can be improved,and the intracranial blood supply of patients with poorly compensated medial cranial circulation and hypoperfusion can be restored to a certain extent.Meanwhile,improvement of cognitive function was definitive in some patients with cognitive dysfunction.To guide the formulation of treatment plans for patients with severe middle cerebral artery stenosis or occlusion.
基金supported by the National Natural Science Foundation of China (No. 81171029)
文摘Summary: This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=-0.037 and P=0.000; P=0.023 and P=-0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
文摘<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. <strong>Methods:</strong> To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. <strong>Results:</strong> There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76);2.98 (2.58, 3.45);2.79 (1.69, 4.59);2.35 (1.93, 2.85);2.25 (1.86, 2.71);2.14 (2.10, 2.18);1.82 (1.62, 2.03);1.54 (1.24, 1.92);1.45 (1.34, 1.56);0.83 (0.78, 0.89). <strong>Conclusion: </strong>Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.