Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Effects of Progressive Muscle Relaxation Training on Anxiety, Depression, and Quality of Life in Patients with Cerebral Small Vessel Disease

Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group(28 patients)and a control group(33 patients)by lottery method.The control group received conventional nursing care,while the observation group received progressive muscle relaxation training interventions in addition to the conventional care.The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Scale(HAMD),and the Stroke-Specific Quality of Life Scale(SS-QOL)were used to compare the effects before the intervention,7 days after the intervention,and 30 days after the intervention.Results:Over time,at different time points after the intervention,the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group(P<0.05).The quality of life scores were significantly higher in the observation group compared to the control group(P<0.05),and these differences were statistically significant.Conclusion:Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.

Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment

BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.

Evaluation of Clinical Outcomes of ses Stent in Patients with Coronary Artery Disease After Intracoronary Stenting in Small Vessels

Background:Limited data are available for sirolimus-eluting stent(SES,Cypher)implantation in patients with coronary artery disease in small vessels.The clinical longtermoutcomes of SES in patients with coronary artery disease after intracoronary stenting in small vessels has not been yet evaluated.

The role of small vessel disease in development of Alzheimer's disease

Classically Alzheimer＇s disease and vascular dementia have been considered as two different entities, with their own clinical criteria, but relatively recent epidemiological and clinicopathological studies suggest an overlap between them sharing not only most of the risk factors and some clinical aspects but also pathophysiological mechanisms. Cerebrovascular lesions, especially small vessel disease （lacunar infarcts, white matter hyperintensities and microbleeds）, may magnify the effects of mild Alzheimer＇s disease pathology and promote the progression of cognitive decline and may also be a precursor of neuronal damage and dementia. ＂Vascular hypothesis＂ of Alzheimer＇s disease would open a window for new approaches and treatments.

Roles of NG2 Glia in Cerebral Small Vessel Disease

Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment

Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Magnetic resonance imaging manifestations of cerebral small vessel disease:automated quantification and clinical application

The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.The CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

Pandemic of the aging society—sporadic cerebral small vessel disease

Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population.The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD.In this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

Clinical management of cerebral small vessel disease:a call for a holistic approach

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(MRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms.Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of SVD.In this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on MRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions.The core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’approach.This approach should integrate clinical expertise in stroke neurology,cognitive,and physical dysfunctions.It requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions.An essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

HTRA1-related autosomal dominant cerebral small vessel disease

Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL).Recently,increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease(CSVD)with an autosomal dominant pattern of inheritance.This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.Methods:We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1,2020.CARASIL probands with genetic diagnosis reported to date were also reviewed.The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.Results:Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included.Compared with typical CARASIL,HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors(P<0.001),a later onset age(P<0.001),and a relatively slower clinical progression.Alopecia and spondylosis can be observed,but less than those in the typical CARASIL.Thirty-five heterozygous mutations in HTRA1 were reported,most of which were missense mutations.Amino acids located close to amino acids 250-300 were most frequently affected,followed by these located near 150∼200.While amino acids 250∼300 were also the most frequently affected region in CARASIL patients,fewer mutations precede the 200th amino acids were detected,especially in the Kazal-type serine protease domain.Conclusions:HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL.The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.

Cerebral small vessel disease caused by PLOD3 mutation:Expanding the phenotypic spectrum of lysyl hydroxylase-3 deficiency

Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysmorphisms,skeletal and eye manifestations,sensorineural hearing loss,and variable skin manifestations.Severe central nervous system involvement has not been reported.Case presentation:A 10-month-old girl was admitted with development delay and clustered epileptic spasms.Hypertelorism,an upturned nose,and low-set ears were noted in physical examination.Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci,extensive abnormal signals in the white matter,and obvious brain atrophy,which was consistent with cerebral small vessel disease(SVD).Electroencephalography suggested hypsarrhythmia.The vertebrae were flattened.The distal end of the metacarpal bone in the left hand was irregular.She was diagnosed with West syndrome.Whole-exome sequencing revealed a novel homozygous variant of c.12161218delCTC(p.L406del)inPLOD3,which was found to be inherited from her heterozygous parents.Conclusion:We report a patient with pathogenicPLOD3 mutation who presented with cerebral SVD.This report expands the phenotypic spectrum of LH3 deficiency.

The Clinical and Angiograghic Outcome of 190 Cases after Stent Placement in Small Coronary Vessels

Objectives To invest the success procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels. Methods 290 patients with selected or emergency stent implantation in small vessels from April, 1997 to March,2002. Total 299 vessels,304 lesions and 316 stents were statisted. The successs rate of procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels were assessed. The patients were followed up 1 month to 4 years. Re-catheter angiography were done in 122/290 patients. Results The narrow rate of lesion dropped from 89% ± 12% before procedure to 5% ±5% after procedure (diameter). 202 patients were followed up 1 month (69.7%). 197/202 cases were survival. 5/202 cases died in 3hrs to 7days. 2/5 cases died of persistent hypotension after procedure. 1/5 case died of acute left heart failure. 2/5 cases died of sudden death. 180 cases were followed up 5 months to 4 years. The non-event survival (NES) rate was 73.3% (132/180). The re-angiography were done in 122 cases. Restenosis happened in 39 cases (30.3%). 37 patients repeated PCI. 2 patients went to CABG. 2 cases got angina recurrence and were proved second time restenosis by re-angiography. The third time PCI was done in 1 patient. The other patients went to CABG. 1 case died of chronic heart failure after 2 years, 1 case suffered acute myocardial infarction on artery stent implanted. Conclusions There are high success rate of procedure and perfect immediate outcome in stent placement in small vessels. Main adverse cardiac events did not increased. Non-event survial was satisfied in long term follow -up. Restenosis rate was showed slightly higher than the one of main vessels.

Pathological Changes of Small Blood Vessels in Maxillofacial Region Following High Velocity Missile Wound:an Experimental Study in Dogs

In order to provide an experimental foundation and pathological base for earlyreconstruction of maxillofacial tissues defects after firearms wound using microsurgicalmethods,an experiment,was made to study the microvascular pathological changesthrough light and electron microscopy observation.In the experiment we found somepathological changes of small vessels in wounded region,such as mierothrombi forma-tion,endothelial loss,internal elastic membrane break and some degenerations,necrosis within endothelial and smooth muscle cells of vessel.The nearer the woundededge was,the more evident injury was.The microvascular injurous range was 3 cm dis-tant from wounded edge,which recovered in 7 days later after wounding.The experi-ment indicated that if we used the vascularized free tissue transfer to repair defects ofmaxillofacial firearms wounds,the pedicles of flap should be anastomosed to distant re-cipient vesseles which could be chosen beyond 3 cm from wounded edge.Thereconstructive operation should be done 7 days later after wound.

中国脑小血管病的神经影像学诊断标准及名词标准化定义——来自中国卒中学会的专家共识

脑小血管病(small vessel disease,SVD)是一类以脑内小血管受损为主的临床影像综合征,可能会导致卒中、血管性认知障碍、神经心理疾病与其他功能障碍等。自2013年血管性神经病变的影像报告标准(standards for reporting vascular changes on neuroimaging,STRIVE)发布以来,SVD的神经影像学特征得到了初步的分类与标准化。然而,在临床实践与科学研究中,对SVD影像特征的认识和应用仍存在诸多不一致和不规范之处。随着对SVD病理生理机制的深入探索与影像技术的不断进步,新的SVD影像特征和定量标志物被相继发现,为SVD的诊断和评估提供了更为全面且精准的信息。在此基础上,STRIVE-2应运而生,以期能更全面地揭示SVD对脑功能与结构的影响。为了规范中国SVD的神经影像学评估和诊断,本共识将在STRIVE-2的基础上,结合中国具体国情,对SVD的神经影像学特征进行深入解读,旨在推动SVD影像学诊断术语的标准化,提高临床诊断的准确性,进一步促进相关领域的研究与进步。

基于fMRI图论网络探索脑小血管病性轻度认知障碍的虚、实证候拓扑属性对照研究

目的基于图论网络探索性分析皮质下脑小血管病性轻度认知障碍虚证、实证的全脑及局部脑网络拓扑属性组间差异。方法前瞻性招募诊断为皮层下小血管病所致轻度血管性认知障碍患者和健康对照,基于GRETNA平台,计算虚证、实证和健康对照比较的组间全局小世界拓扑属性和局部节点强度、节点效率的组间差异。结果三组均具有小世界属性,但仅实证组患者在稀疏度为0.05-0.26内小世界属性δ显著低于对照组(P<0.05);同时,涉及额、顶及小脑等多个脑区的节点效率和节点强度指标均显著区分实证组、虚证组,但虚证患者在节点效率上无阳性脑区(P>0.05),在节点强度上仅表现为少数脑区的节点效率增高(P<0.05)。结论实组在全局拓扑属性及局部拓扑属性上均显著有别于虚证组,说明虚实证候具有显著差异的影像表型,为进一步探讨中医证候在疾病生物学分型的作用提供研究基础。

体位性低血压与脑小血管病综合评分的相关性研究

目的探究脑小血管病(cerebral small vessel disease,CSVD)患者体位性低血压(orthostatic hypotension,OH)的有无及其类型与CSVD综合评分之间的关系。方法连续入组2021年3月至2023年9月期间的CSVD住院患者460例,根据有无OH及不同OH亚型将所有受试者分为无OH组、早期OH(early OH,EOH)组及延迟/持续OH(delayed/prolonged OH,DPOH)组。采用0~4分的五分制评分方法评估CSVD综合评分。分别分析不同OH分组与腔隙、脑白质高信号(white matter hyperintensities,WMH)评分、脑微出血(cerebral microbleeds,CMBs)、基底节区血管周围间隙(basal ganglia-perivascular spaces,BG-PVS)及CSVD综合评分的相关性。结果入组患者中EOH和DPOH的发生率分别为10.00%和17.17%。各组间存在腔隙的比例、BG-PVS等级及CSVD综合评分的分布差异有统计学意义(P<0.01),校正年龄、性别、高血压及卧位舒张压后,DPOH是腔隙(OR=2.421,95%CI:1.372~4.271,P=0.002)、严重BG-PVS(OR=1.714,95%CI:1.074~2.740,P=0.024)及更高CSVD综合评分(OR=1.791,95%CI:1.140~2.818,P=0.012)的独立危险因素。结论在CSVD患者中,DPOH较EOH更多见,且是CSVD综合评分增加的独立危险因素。