Exploring the therapeutic potential of Qi Teng Mai Ning recipe in ischemic stroke and vascular cognitive impairment

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.

Diagnosis advances in vascular cognitive impairment

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.

Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

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.

Sevoflurane effects on cyclic adenosine monophosphate response element binding protein,phosphorylated cyclic adenosine monophosphate response element binding protein,and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat

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.

Expert Consensus on the Clinical Application of Tianma Xingnao Capsule in the Treatment of Vascular Cognitive Impairment and Neuropathic Headache

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.

Disrupted functional connectivity of default mode network and executive control network in patients with vascular cognitive impairment, no dementia

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.

Advances in the Pathogenesis of Vascular Cognitive Impairment

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.

Clinical Study of Endovascular Treatment of Severe Middle Cerebral Artery Stenosis or Occlusion and Vascular Cognitive Impairment

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.

Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model

Objective To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia. Methods The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion （BCCAO）. The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group （n = 6）, model group （subdivided into 3 groups： 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6）, and minocycline group （subdivided into 3 groups： 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6）. Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein （GFAP） was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 （COX-2） and nuclear factor-kappaB （NF-κB） were measured by immunohistochemistry. IL-1β and TNF-α levels were tested with ELISA method. Results Levels of GFAP, COX- 2, NF-κB, IL-1β and TNF-α were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline. Conclusion Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.

Original article：A new diagnostic algorithm for vascular cognitive impairment： the proposed criteria and evaluation of its reliability and validity

Background Vascular cognitive impairment （VCI） is considered to be the most common pattern of cognitive impairment. We aimed to devise a diagnostic algorithm for VCI, and evaluate the reliability and validity of our proposed criteria. Methods We based our new algorithm on previous literature, a Delphi consensus method, and preliminary testing. First, successive 100 patients with cerebrovascular disease （CVD） in hospital underwent a structured medical examination. Twenty-five case vignettes fulfilled the proposed criteria of diagnosis for probable or possible VCI were divided into three subtype categories： vascular cognitive impairment, no dementia （VCIND）, vascular dementia （VaD） or mixed VCI/Alzheimer＇s disease （AD）. Inter-raters reliability was assessed using a Fleiss kappa analysis. Convergent validity was also evaluated by correlation coefficients （r） between the proposed key points for each subtype and the currently accepted criteria. Forty-five patients with probable VCI were examined to determine the accuracy of identification for each subtype. Results The proposed criteria showed clinical diagnostic validity for VCI, and were able to define probable, possible and definite VCI, three VCI subtypes, and vascular causes. There was good consensus between experts （Cronbach＇s a=0.96 for both rounds）. Significant moderate to good items-total correlations were found for two questionnaires （50-r range, 0.40-0.97 and 0.41-0.99, respectively）. Significant slight and moderate inter-raters reliability were obtained for VCI （k=0.13） and three VCI subtypes （k=0.45）. Furthermore, good convergent validity was observed in a comparison of significant correlations between criteria： good （4-r range, 0.75-0.92） to perfect （3-r=1.00） validity for the VCIND subtype, and moderate to good validity for the VaD subtype （1-r=0.46; 5-r range, 0.76-0.92） and for the mixed VCI/AD subtype （r=0.92 and 1.00; 4-r range, 0.47-0.70）. Importantly, the area under receiver operating characteristic （ROC） curves for the subtypes of VCIND, VaD and mixed VCI/AD were 0.85, 0.67 and 0.93, respectively. Conclusion Our results suggest that the new VCI diagnostic algorithm might be a suitable clinical approach for assessing stroke patients.

Changes in HIF-1α, VEGF, NGF and BDNF Levels in Cerebrospinal Fluid and TheirRelationship with Cognitive Impairment in Patients with Cerebral Infarction

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.

Meta-Analysis of Risk Factors of Vascular Cognitive Disorder in Acute Cerebral Infarction Patients

Objectives: 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. Methods: 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. Results: 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). Conclusion: 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.

Lacunar infarction with leukoaraiosis may aggravate cognitive dysfunction

This study semi-quantitatively analyzed the effects of leukoaraiosis.Patients with moderate or severe lacunar infarction were found to exhibit low scores on the Montreal Cognitive Assessment Scale （F=12.02,P=0.000）,and prolonged P300 Cz2.0 latency （F=16.04,P=0.000）.Correlation analysis revealed that the occurrence of leukoaraiosis was negatively correlated with Montreal Cognitive Assessment scores （r=-0.416,P=0.000）,and positively correlated with P300 Cz2.0 latency （r=0.538,P=0.000）.These findings indicate that leukoaraiosis aggravates cognitive impairment in patients with lacunar infarction,such that more severe leukoaraiosis is associated with more severe cognitive decline.

Neurogranin as an important regulator in swimming training to improve the spatial memory dysfunction of mice with chronic cerebral hypoperfusion

Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;however,the specific mechanism has remained inconclusive.And recent studies found that neurogranin(Ng)is a potential biomarker for cognitive impairment.This study aims to investigate the underlying role of Ng in swimming training to improve cognitive impairment.Methods:To test this hypothesis,the clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(Cas9)system was utilized to construct a strain of Ng conditional knockout(Ng cKO)mice,and bilateral common carotid artery stenosis(BCAS)surgery was performed to prepare the model.In Experiment 1,2-month-old male and female transgenic mice were divided into a control group(wild-type littermate,n=9)and a Ng cKO group(n=9).Then,2-month-old male and female C57BL/6 mice were divided into a sham group(C57BL/6,n=12)and a BCAS group(n=12).In Experiment 2,2-month-old male and female mice were divided into a sham group(wild-type littermate,n=12),BCAS group(n=12),swim group(n=12),BCAS+Ng cKO group(n=12),and swim+Ng cKO group(n=12).Then,7 days after BCAS,mice were given swimming training for 5 weeks(1 week for adaptation and 4 weeks for training,5 days a week,60 min a day).After intervention,laser speckle was used to detect cerebral blood perfusion in the mice,and the T maze and Morris water maze were adopted to test their spatial memory.Furthermore,electrophysiology and Western blotting were conducted to record long-term potential and observe the expressions of Ca^(2+)pathway-related proteins,respectively.Immunohistochemistry was applied to analyze the expression of relevant markers in neuronal damage,inflammation,and white matter injury.Results:The figures showed that spatial memory impairment was detected in Ng cKO mice,and a sharp decline of cerebral blood flow and an impairment of progressive spatial memory were observed in BCAS mice.Regular swimming training improved the spatial memory impairment of BCAS mice.This was achieved by preventing long-term potential damage and reversing the decline of Ca^(2+)signal transduction pathway-related proteins.At the same time,the results suggested that swimming also led to improvements in neuronal death,inflammation,and white matter injury induced by CCH.Further study adopted the use of Ng cKO transgenic mice,and the results indicated that the positive effects of swimming training on cognitive impairments,synaptic plasticity,and related pathological changes caused by CCH could be abolished by the knockout of Ng.Conclusion:Swimming training can mediate the expression of Ng to enhance hippocampal synaptic plasticity and improve related pathological changes induced by CCH,thereby ameliorating the spatial memory impairment of vascular cognitive impairment.

Effects of electroacupuncture on rats with cognitive impairment:An iTRAQ-based proteomics analysis

Objective The study explores the effects of electroacupuncture(EA)at the governing vessel(GV)on proteomic changes in the hippocampus of rats with cognitive impairment.Methods Healthy male rats were randomly divided into 3 groups:sham,model and EA.Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups.Rats in the EA group were treated with EA at Shenting(GV24)and Baihui(GV20)for 7 d.Neurological deficit was scored using the Longa scale,the learning and memory ability was detected using the Morris water maze(MWM)test,and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation(iTRAQ).The Western blot(WB)analysis was used to detect the proteins and validate the results of iTRAQ.Results Compared with the model group,the neurological deficit score was significantly reduced,and the escape latency in the MWM test was significantly shortened,while the number of platform crossings increased in the EA group.A total of 2872 proteins were identified by iTRAQ.Differentially expressed proteins(DEPs)were identified between different groups:92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group,while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group.Most of the DEPs were involved in oxidative phosphorylation,glycolipid metabolism and synaptic transmission.Furthermore,we also verified 4 DEPs using WB technology.Although the WB results were not exactly the same as the iTRAQ results,the expression trends of the DEPs were consistent.The upregulation of heat-shock proteinβ1(Hspb1)was the highest in the EA group compared to the model group.Conclusion EA can effect proteomic changes in the hippocampus of rats with cognitive impairment.Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis

OBJECTIVE： To treat patients with vascular mild cognitive impairment （VMCI） using traditional Chinese medicine （TCM）, it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis （LTA）. METHOD： A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules. RESULTS： Eight syndrome types are identified： Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types. CONCLUSION： A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

Selective Aberrant Functional–Structural Coupling of Multiscale Brain Networks in Subcortical Vascular Mild Cognitive Impairment

Subcortical vascular mild cognitive impairment(svMCI)is a common prodromal stage of vascular dementia.Although mounting evidence has suggested abnormalities in several single brain network metrics,few studies have explored the consistency between functional and structural connectivity networks in svMCI.Here,we constructed such networks using resting-state f MRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls.The functional networks were then parcellated into topological modules,corresponding to several well-defined functional domains.The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level(whole brain and modular level).We found no significant intergroup differences in the functional–structural coupling within the whole brain;however,there was significantly increased functional–structural coupling within the dorsal attention module and decreased functional–structural coupling within the ventral attention module in the svMCI group.In addition,the svMCI patients demonstrated decreased intramodular connectivity strength in the visual,somatomotor,and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network,mainly linking the visual,somatomotor,dorsal attention,ventral attention,and frontoparietal control modules.There was no significant correlation between the altered module-level functional–structural coupling and cognitive performance in patients with svMCI.These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.

Modeling subcortical ischemic white matter injury in rodents:unmet need for a breakthrough in translational research

Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.

Vascular contribution to cognition in stroke and Alzheimer's disease

Vascular factors to cognitive impairment in degenerative on nondegenerative diseases have been reported, examined, and debated for several decades. The various definitions of cognitive impairment due to vascular origins will make these results diverse. During this review, we are going to report currently update information of vascular contributions to cognitive function, in clinical or neuroimaging findings. Risks factors and their managements also will be discussed and reported to have a comprehensive review.

Biomarker-based diagnosis of cognitive disorders in a case series

The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-tau and amyloid beta peptide) have received much attention, since they can detect the biochemical fingerprint of Alzheimer's disease and serve as a diagnostic aid for correct diagnosis of cognitive disorders during life. In this case series, we present 6 examples of patients with cognitive impairment of various types and severities and how biomarker data were helpful in every day diagnostic approach, combined with clinical, neuropsychological and imaging data and based on the most recent guidelines and recommendations.