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 a...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.展开更多
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 th...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.展开更多
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 patholo...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.展开更多
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 prospectiv...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.展开更多
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,perivas...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.展开更多
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 ...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.展开更多
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 leuko...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.展开更多
Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often a...Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often asymptomatic in its early stages.However,as CsvD develops,brain disorders may occur,such as stroke,cognitive dysfunction,dyskinesia and mood disorders,and heart,kidney,eye and systemic disorders.As the population continues to age,the burden of CsvD is increasing.Moreover,there is an urgent need for better screening methods and diagnostic markers for CsvD,in addition to preventive and asymptomatic-and mild-stage treatments.Integrative medicine(IM),which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives,has unique advantages for the prevention and treatment of CsvD.In this review,we summarize the biological markers,ultrasound and imaging features,disease-related genes and risk factors relevant to CsvD diagnosis and screening.Furthermore,we discuss IM-based csvD prevention and treatment strategies to stimulate further research in this field.展开更多
Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological ba...Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.展开更多
In 1987, Hachinski et al. [1] proposed Leukoaraiosis (LA) as an imaging academic term. Since then, LA and other cerebrovascular diseases have become the research focus of scholars at home and abroad. However, the mole...In 1987, Hachinski et al. [1] proposed Leukoaraiosis (LA) as an imaging academic term. Since then, LA and other cerebrovascular diseases have become the research focus of scholars at home and abroad. However, the molecular, cellular and pathogenesis of cerebrovascular disease are still unclear. Cerebral small vessel disease is caused by the lesions of perforating arteries, capillaries and veins of the brain. Modern imaging technology makes it possible to classify these diseases that can not be directly distinguished in clinical practice. The imaging features of cerebral infarction include cerebral microvascular atrophy. At present, a large number of studies have been carried out around LA, such as the pathogenesis, risk factors, imaging manifestations and classification, pathophysiological changes, hemodynamics, gene polymorphism and so on. In addition, although LA belongs to the category of cerebral small vessel disease, more scholars believe that there are countless links between large artery atherosclerosis and LA, and to some extent, have the same pathogenesis. This paper reviews the following aspects.展开更多
Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related an...Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.展开更多
Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the presen...Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.展开更多
Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of t...Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82274611 (to LZ),82104419 (to DM)Capital Science and Technology Leading Talent Training Project,No.Z1 91100006119017 (to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803 (to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006 (to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017 (to DM)Beijing Gold-Bridge Project,No.ZZ20145 (to DM)。
文摘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.
文摘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.
基金supported by grants from the National Natural Science Foundation of China(32100798)the China Postdoctoral Science Foundation(2021M700821).
文摘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.
基金supported by the National Key Research and Development Program of China(2016YFB1001402)National Natural Science Foundation of China(81971138)+2 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-3-008)Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)Research Foundation for Young Scholars of Peking Union Medical College Hospital(PUMCH201911275)。
文摘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.
基金supported partially by grants from the National Key Research and Development Program of China(No.2016YFC1300600)Research Grants Council of the Hong Kong Special Administrative Region,China(No.CUHK 14204117)。
文摘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.
基金the National Key Research and Development Program of China(No.2016YFC13600600).
文摘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.
基金supported by grants from the National Key Research and Development Program of China(No.2016YFC0901004)the CAMS Innovation Fund for Medical Sciences(CIFMS#2017-I2M-3-008)。
文摘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.
基金Supported by the National Natural Science Foundation of China(No.82074507 and No.81904263)Chinese Medicine Research Project Plan of Fujian Province in 2021-2024(No.2021ZYJC02)Clinical Special Project of Fujian University of Traditional Chinese Medicine(No.XB2021038)。
文摘Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often asymptomatic in its early stages.However,as CsvD develops,brain disorders may occur,such as stroke,cognitive dysfunction,dyskinesia and mood disorders,and heart,kidney,eye and systemic disorders.As the population continues to age,the burden of CsvD is increasing.Moreover,there is an urgent need for better screening methods and diagnostic markers for CsvD,in addition to preventive and asymptomatic-and mild-stage treatments.Integrative medicine(IM),which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives,has unique advantages for the prevention and treatment of CsvD.In this review,we summarize the biological markers,ultrasound and imaging features,disease-related genes and risk factors relevant to CsvD diagnosis and screening.Furthermore,we discuss IM-based csvD prevention and treatment strategies to stimulate further research in this field.
文摘Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.
文摘In 1987, Hachinski et al. [1] proposed Leukoaraiosis (LA) as an imaging academic term. Since then, LA and other cerebrovascular diseases have become the research focus of scholars at home and abroad. However, the molecular, cellular and pathogenesis of cerebrovascular disease are still unclear. Cerebral small vessel disease is caused by the lesions of perforating arteries, capillaries and veins of the brain. Modern imaging technology makes it possible to classify these diseases that can not be directly distinguished in clinical practice. The imaging features of cerebral infarction include cerebral microvascular atrophy. At present, a large number of studies have been carried out around LA, such as the pathogenesis, risk factors, imaging manifestations and classification, pathophysiological changes, hemodynamics, gene polymorphism and so on. In addition, although LA belongs to the category of cerebral small vessel disease, more scholars believe that there are countless links between large artery atherosclerosis and LA, and to some extent, have the same pathogenesis. This paper reviews the following aspects.
基金National Key Research and Development Program of China(No.2016YFC1300500-505)。
文摘Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.
文摘Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.
基金supported by grants from the 1·3·5 project for disciplines of excellence,Clinical Research Incubation Project,West China Hospital,Sichuan University(No.2020HXFH012)the National Natural Science Foundation of China(Nos.82071320 and 81870937)。
文摘Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.
