Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases

Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Multi-target mechanism of triphala in cardio-cerebral vascular diseases based on network pharmacology

OBJECTIVE Numerous references made clear that triphala is revered as a multiuse therapeutic and perhaps even panacea historically.Nevertheless,the protective mechanism of triphala on cardio-cerebral vascular diseases(CCVDs)remains not comprehensive understanding.Hence,a network pharmacology-based method was suggested in this study to address this problem.METHODS This study was based on network pharmacology and bioinformatics analysis.Information on compounds in herbal medicines of triphala formula was acquired from public databases.Oral bioavailability as well as drug-likeness were screened by using absorption,distribution,metabolism,and excretion(ADME)criteria.Then,components of triphala,candidate targets of each component and known therapeutic targets of CCVDs were collected.Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources.In addition,key targets and pathway enrichment were analyzed by STRING database and DAVID database.Moreover,we verified three of the key targets(PTGS2,MMP9 and IL-6)predicted by using Western blotting analysis.RESULTS Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening,and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs.And 10 compounds,which actually linked to more than three genes,are determined as crucial chemicals.Core genes in this network were IL-6,TNF,VEGFA,PTGS2,CXCL8,TP53,CCL2,IL-10,MMP9 and SERPINE1.And pathways in cancer,TNF signaling path⁃way,neuroactive ligand-receptor interaction,etc.related to CCVDs were identified.In vitro experiments,the results indi⁃cated that compared with the control group(no treatment),PTGS2,MMP9 and IL-6 were up-regulated by treatment of 10μg·L^-1 TNF-α,while pretreatment with 20-80 mg·L^-1 triphala could significantly inhibit the expression of PTGS2,MMP9 and IL-6.With increasing Triphala concentration,the expression of PTGS2,MMP9 and IL-6 decreased.CON⁃CLUSION Complex components and pharmacological mechanism of triphala,and obtained some potential therapeutic targets of CCVDs,which could provide theoretical basis for the research and development of new drugs for treating CCVDs.

Correlation of MRI-determined small bowel Crohn’s disease categories with medical response and surgical pathology

AIM: To determine whether magnetic resonance imaging (MRI) can be used to categorize small bowel Crohn's disease (SB CD) into groups that correlate with response to medical therapy and surgical pathology.METHODS: Data was collected from all patients with MRI evidence of SB CD without significant colonic disease over a 32-mo period. Two radiologists, blinded to clinical findings, evaluated each MRI and grouped them based on bowel wall thickness and wall enhancement. These categories were: (1) "fibrosis", (2) "mild segmental hyper-enhancement and mild wall thickening", (3) "mild segmental hyper-enhancement and marked wall thickening", (4) "marked segmental transmural hyper-enhancement". Patient response to additional medical therapy post-MRI was prospectively determined at 8-wk. Non-responders underwent endoscopy and were offered therapeutic endoscopy or surgery. Surgical pathology was assessed against the MRI category. RESULTS: Fifty-five patients were included. Females and category "2" patients were more likely, and patients with luminal narrowing and hold-up less likely, to respond to medical therapy (P < 0.05). Seventeen patients underwent surgery. The surgical pathologicalfindings of fibrosis and the severity of inflammation correlated with the MRI category in all cases.CONCLUSION: Our fi ndings suggest that SB CD can be grouped by the MRI f indings and that these groups are associated with patients more likely to respond to continued medical therapy. The MRI categories also correlated with the presence and level of intestinal inflammation and fibrosis on surgical pathology, and may be of prognostic use in the management of CD patients.

Characterization of cerebrovascular changes in Alzheimer's disease mice by photoacoustic imaging

The cerebral vasculature plays a significant role in the development of Alzheimer's disease(AD),however,the specific association between them remains unclear.In this paper,based on the benefits of photoacoustic imaging(PAI),including label-free,high-resolution,in vivo imaging of vessels,we investigated the structural changes of cerebral vascular in wild-type(WT)mice and AD mice at different ages,analyzed the characteristics of the vascular in different brain regions,and correlated vascular characteristics with cognitive behaviors.The results showed that vascular density and vascular branching index in the cortical and frontal regions of both WT and AD mice decreased with age.Meanwhile,vascular lacunarity increased with age,and the changes in vascular structure were more pronounced in AD mice.The trend of vascular dysfunction aligns with the worsening cognitive dysfunction as the disease progresses.Here,we utilized in vivo PAI to analyze the changes in vascular structure during the progression of AD,elucidating the spatial and temporal correlation with cognitive impairment,which will provide more intuitive data for the study of the correlation between cerebrovascular and the development of AD.

Neutrophil-to-lymphocyte ratio in occlusive vascular diseases： the literature review of the past 10 years

BACKGROUND: This study aims to evaluate the results of studies investigating neutrophilto-lymphocyte ratio(NLR) and to identify the prognostic and diagnostic value of NLR in occlusive vascular diseases.METHODS: With the aim of identifying the studies related to NLR, a search was performed on http://www.ncbi.nlm.nih.gov/pubmed by using the key words "neutrophil lymphocyte ratio" between January 2005 and December 2014. All of the original articles were evaluated according to date of publications, countries, clinics and topics. Studies about occlusive vascular diseases were evaluated according to their qualifications, review methods and results. SPSS for Windows 16.0 was used in data analysis and data were expressed as mean, standard deviation and percentage.RESULTS: A total of 735 original research articles were investigated. The number of publications have shown a regular logarithmic increase over the years. Thirty-two percent of all publications were performed by clinics in Turkey and 56.4% were performed by general-oncological surgery and cardiology clinics. A total of 107 publications were identified to be about occlusive vascular diseases, 80.3% of these publications were found to be prognostic and 19.6% to be diagnostic, 82.2% of them were found to be planned as retrospective and 17.7% as prospective. In 95.3% of prognostic publications, there was a positive correlation between high NLR values at admission and poor prognosis. In 95.3% of diagnostic publications high NLR values at admission were identifi ed to be signifi cant diagnostically.CONCLUSION: Elevated neutrophil-to-lymphocyte ratio at admission, could be used as a diagnostic and/or prognostic parameter in occlusive vascular diseases.

LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION:FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

Dynamic Pathology and Antigen Location Study on Broiler Breeders with Coinfection of Marek's Disease Virus and Reticuloendotheliosis Virus

To further understand the generation and development of coinfection of Marek＇s disease virus （MDV） and reticuloendotheliosis virus （REV） in broiler breeders, and then find the method and optimal time of differential diagnosis for complex clinic multiple infection, the authors studied the pathohistological changes, apoptosis, immunohistochemistry （immunofluorescence）, and ultrastructure of tumor tissues of broiler breeders inoculated with MDV and REV. The study showed that proliferation of small lymphocytes was seen in the main organs at the age of 1 week, then immature lymphocytes, all kinds of lymphocytes, primitive reticulum cells, and Marek＇s disease cells （MDCs） were observed at 2-9 weeks. Apoptosis of lymphocytes could not be seen until the age of 10 weeks in the immune system. Immunohistochemistry detection showed that the positive signs of MDV and REV antigen were observed in the main organs at 2 weeks of age. Multi-morphology lymphocytes, MDV, and REV, mitotic figures and apoptosis of lymphocytes were observed with the help of transmission electron microscopy. MDV cooperating with REV promotes the course of disease of coinfection. Differential diagnosis can be done by immunohistochemistry in the early stage （before 2 weeks）, and histopathology in the late stage （post 4 weeks）. MDCs, primitive reticulum cells, immature lymphocytes, and two kinds of virions can serve as a basis for bistopathology differential diagnosis.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Putative roles of cathepsin B in Alzheimer's disease pathology: the good, the bad, and the ugly in one?

Alzheimer＇s disease（AD）is a fatal progressive neurodegenerative disorder characterized by loss in memory,cognition,and executive function and activities of daily living.AD pathogenesis has been shown to involve loss of neurons and synapses,cholinergic deficits,amyloid-beta protein（Aβ）deposition,tau protein hyperphosphorylation, and neuroinflammation.

Evaluation of left ventricular systolic function in type 2 diabetes mellitus patients with and without peripheral vascular disease

BACKGROUND Peripheral vascular disease(PVD)is a common complication of type 2 diabetes mellitus(T2DM).Patients with T2DM have twice the risk of PVD as nondiabetic patients.AIM To evaluate left ventricular(LV)systolic function by layer-specific global longitudinal strain(GLS)and peak strain dispersion(PSD)in T2DM patients with and without PVD.METHODS Sixty-five T2DM patients without PVD,57 T2DM patients with PVD and 63 normal controls were enrolled in the study.Layer-specific GLS[GLS of the epimyocardium(GLSepi),GLS of the middle myocardium(GLSmid)and GLS of the endocardium(GLSendo)]and PSD were calculated.Receiver operating characteristic(ROC)analysis was performed to calculate the sensitivity and specificity of LV systolic dysfunction in T2DM patients with PVD.We calculated Pearson’s correlation coefficients between biochemical data,echocardiographic characteristics,and layer-specific GLS and PSD.RESULTS There were significant differences in GLSepi,GLSmid and GLSendo between normal controls,T2DM patients without PVD and T2DM patients with PVD(P<0.001).Trend tests revealed a ranking of normal controls>T2DM patients without PVD>T2DM patients with PVD in the absolute value of GLS(P<0.001).PSD differed significantly between the three groups,and the trend ranking was as follows:normal controls<T2DM patients without PVD<T2DM patients with PVD(P<0.001).ROC analysis revealed that the combination of layer-specific GLS and PSD had high diagnostic efficiency for detecting LV systolic dysfunction in T2DM patients with PVD.Lowdensity lipoprotein cholesterol was positively correlated with GLSepi,GLSmid and PSD(P<0.05),while LV ejection fraction was negatively correlated with GLSepi,GLSmid and GLSendo in T2DM patients with PVD(P<0.01).CONCLUSION PVD may aggravate the deterioration of LV systolic dysfunction in T2DM patients.Layer-specific GLS and PSD can be used to detect LV systolic dysfunction accurately and conveniently in T2DM patients with or without PVD.

Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

Cerebellar pathology in motor neuron disease:neuroplasticity and neurodegeneration

Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition.The clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,including cerebellar pathology.Post-mortem and neuroimaging studies primarily focus on the chara cterization of supratentorial disease,des pite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis.Cardinal clinical features of amyotrophic lateral sclerosis,such as dysarthria,dysphagia,cognitive and behavioral deficits,saccade abnormalities,gait impairment,respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology.This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral scle rosis.Structural imaging studies consistently capture cerebellar grey matter volume reductions,diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alte rations and functional imaging studies commonly report increased functional connectivity with supratentorial regions.Increased functional connectivity is commonly interpreted as evidence of neuro plasticity representing compensatory processes despite the lack of post-mortem validation.There is a scarcity of post-mortem studies focusing on cerebellar alte rations,but these detect pTDP-43 in cerebellar nuclei.Ce rebellar pathology is an overloo ked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms,wides p read connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.

Developing a better mouse model of Alzheimer disease with clinically relevant phenotypes in tau pathology

OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.

Simple pain measures reveal psycho-social pathology in patients with Crohn's disease

To determine whether pain has psycho-social associations in adult Crohn’s disease (CD) patients.METHODSPatients completed demographics, disease status, Patient Harvey-Bradshaw Index (P-HBI), Short Form Health Survey (SF-36), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and five socio-psychological questionnaires: Brief Symptom Inventory, Brief COPE Inventory, Family Assessment Device, Satisfaction with Life Scale, and Work Productivity and Activity Impairment Questionnaire. Pain sub-scales in P-HBI, SF-36 and SIBDQ measures were recoded into 4 identical scores for univariate and multinomial logistic regression analysis of associations with psycho-social variables.RESULTSThe cohort comprised 594 patients, mean age 38.6 ± 14.8 years, women 52.5%, P-HBI 5.76 ± 5.15. P-HBI, SF-36 and SIBDQ broadly agreed in their assessment of pain intensity. More severe pain was significantly associated with female gender, low socio-economic status, unemployment, Israeli birth and smoking. Higher pain scores correlated positively with psychological stress, dysfunctional coping strategies, poor family relationships, absenteeism, presenteeism, productivity loss and activity impairment and all WPAI sub-scores. Patients exhibiting greater satisfaction with life had less pain. The regression showed increasing odds ratios for psychological stress (lowest 2.26, highest 12.17) and female gender (highest 3.19) with increasing pain. Internet-recruited patients were sicker and differed from hardcopy questionnaire patients in their associations with pain.CONCLUSIONPain measures in P-HBI, SF-36 and SIBDQ correlate with psycho-social pathology in CD. Physicians should be aware also of these relationships in approaching CD patients with pain.

Molecular events in the jaw vascular unit:A traditional review of the mechanisms involved in inflammatory jaw bone diseases

Inflammatory jaw bone diseases are common in stomatology,including periodontitis,peri-implantitis,medication-related osteonecrosis of the jaw,radiation osteomyelitis of the jaw,age-related osteoporosis,and other specific infections.These diseases may lead to tooth loss and maxillofacial deformities,severely affecting patients'quality of life.Over the years,the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge.Therefore,exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies.Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types,including osteoblast-associated cells,immune cells,blood vessels,and lymphatic vessels.However,the role of these different cells in the inflammatory process and the'rules'with which they interact are still not fully understood.Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases,few articles offer a perspective of integration.Here,we review the changes and mechanisms of various cell types in inflammatory jaw diseases,with the hope of providing insights to drive future research in this field.

Genetic variants associated with pathological changes in Alzheimer's diseases

Alzheimer's disease(AD)is the most prevalent dementia partially driven by genetics.Recently,a meta-analysis of large scale genome-wide association studies has identified a quantity of AD risk genes.To further investigate the correlation between the genetic variants and pathological progress,we examined 94 brain samples in the Chinese population from the National Human Brain Bank for Development and Function.

Complications of Ziv-Aflibercept in Choroidal and Retinal Vascular Diseases

Introduction: The modern ophthalmology trends are changing rapidly every day with the introduction of much newer studies and research. Numerous anti-vascular endothelial growth factors (VEGF) are utilized as the mainstay in the treatment of intraocular vascular pathologies. The rationale of this study is to add to the literature regarding the safety and efficacy profile of the ziv-aflibercept as there is insubstantial data in patients with intraocular vascular pathologies being treated with this injection with prime focus on the complications of the injection. Materials and Methods: A prospective observational study was conducted at Opthalmology Department, Lahore General Hospital, Lahore between 14 August 2018 and 23 December 2019. Patients with choroidal and retinal vascular diseases like diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO) who had no active infection of eye and had no history of myocardial infarction or cerebrovascular accident were added in this study. Results: Best-corrected visual acuity was significantly improved at 4, 8, and 12 weeks as compared to the baseline (p Conclusion: The use of ziv-aflibercept injection via intravitreal route under aseptic conditions for choroidal and retinal vascular diseases is effective as well as safe with mild and treatable ocular side effects.

Arterial hypertension,cerebrovascular diseases and dementia

Arterial hypertension(AH)is the most relevant risk factor for acute cerebrovascular disease in general.However,the prevalence of AH is not the same for the different stroke subtypes and is particularly high in lacunar infarcts and atherothrombotic stroke,low in infarcts of unusual cause and undetermined origin,and intermediate in cardioembolic stroke.This risk factor has also been related to vascular dementia and Alzheimer’s disease and their pathological manifestations(senile plaques,neurofibrillary tangles,hippocampal atrophy).The mechanisms linking AH to Alzheimer’s disease remain to be elucidated but some recent studies showed that white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association.Hypertension-associated pathological changes in the brain and its vasculature include vascular remodelling and impaired cerebral autoregulation like hypoperfusion,ischemia and hypoxia,which may initiate the pathological process of Alzheimer’s disease and the expression of dementia.Therefore,prompt diagnosis and adequate control of hypertension and different vascular risk factors are the rational basis for a more effective strategy in the secondary prevention of cerebrovascular disease and dementia.