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
Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 pa...Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.展开更多
Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cogniti...Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients(29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits(odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall(odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.展开更多
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)...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.展开更多
Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many...Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth Peoples Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).展开更多
Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the most common form of dementia worldwide.As age is the main risk factor,>97%of all AD cases are of sporadic origin,potentiated by various ri...Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the most common form of dementia worldwide.As age is the main risk factor,>97%of all AD cases are of sporadic origin,potentiated by various risk factors associated with life style and starting at an age>60 years.Only<3%of AD cases are of genetic origin caused by mutations in the amyloid precursor protein or Presenilins 1 or 2,and symptoms already start at an age<30 years.In order to study progression of AD,as well as therapeutic strategies,mouse models are state-of-the-art.So far many transgenic mouse models have been developed and used,with mutations in the APP or presenilin or combinations(3×Tg,5×Tg).However,such transgenic mouse models more likely mimic the genetic form of AD and no information can be given how sporadic forms develop.Several risk genes,such as Apolipoprotein E4 and TREM-2 enhance the risk of sporadic AD,but also many risk factors associated with life style(e.g.,diabetes,hypercholesterolemia,stress)may play a role.In this review we discuss the current situation regarding AD mouse models,and the problems to develop a sporadic mouse model of AD.展开更多
目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、...目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,根据磁共振DWI分为近期皮质下小梗死(RSSI)组和非RSSI组,统计RSSI的部位和数目。比较两组患者的一般人口学资料、临床资料、认知功能,分析RSSI影像学特征与认知功能的关系。结果 共纳入CSVD患者181例,RSSI组91例,非RSSI组90例。RSSI组与非RSSI组相比,BMI高[(25.43±3.53)kg/m^(2) vs(24.27±3.33)kg/m^(2),t=2.228, P=0.027],收缩压高[(145.3±16.2)mmHg vs(139.6±20.2)mmHg,t=2.013,P=0.046],MoCA总分较低[22(18.8,26) vs 24(21,27),Z=-1.980,P=0.048],视空间与执行能力[3(2,4) vs 4(3,5),Z=-2.756,P=0.006]、语言[2(2,3) vs 2(1,2), Z=-2.020,P=0.043]、抽象[2(1,2) vs 2(1,2)分,Z=-2.052,P=0.04]得分均较低,差异均具有显著性统计学意义(P<0.05)。RSSI基底节梗死组与非RSSI组相比,MoCA总分较低[21(17,23) vs 24(21,27),Z=-2.018,P=0.044],视空间与执行[3(1.5,3.5) vs 4(3,5),Z=-2.601,P=0.009]得分较低,RSSI脑干梗死组与非RSSI组相比,视空间与执行[3(2,4) vs 4(3,5),Z=-2.325,P=0.020]、语言[2(1,2) vs 2(2,3),Z=-2.338,P=0.019]得分较低,差异具有显著性统计学意义。结论 CSVD患者中RSSI可导致认知功能障碍,与RSSI梗死部位相关,RSSI不同梗死部位导致不同的认知损害模式。预防RSSI发生,对于预防CSVD相关认知功能障碍具有重要意义。展开更多
目的探究水蛭饮片治疗脑小血管病(Cerebral Small Vessel Disease,CSVD)所致认知障碍患者的临床疗效。方法方便选取2020年10月—2023年6月广西壮族自治区民族医院神经内科收治的120例CSVD所致认知障碍患者为研究对象,以随机数表法分为...目的探究水蛭饮片治疗脑小血管病(Cerebral Small Vessel Disease,CSVD)所致认知障碍患者的临床疗效。方法方便选取2020年10月—2023年6月广西壮族自治区民族医院神经内科收治的120例CSVD所致认知障碍患者为研究对象,以随机数表法分为对照组和观察组,各60例。对照组实施内科常规西药基础治疗,观察组在对照组治疗基础上增加中药水蛭口服治疗。观察并对比两组的治疗结果。结果治疗后与对照组相比,观察组最小量认知评估量表(Mini Mental State Examination,MMSE)评分、蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)评分更高,差异有统计学意义(P均<0.05)。观察组临床治疗有效率(86.67%)显著高于对照组(71.67%),差异有统计学意义(χ^(2)=4.093,P<0.05)。治疗后与对照组相比,观察组的白细胞介素-6(Interleukin-6,IL-6)和超敏-C反应蛋白(High Sensitive C-reactive Protein,hs-CRP)水平更低,差异有统计学意义(P均<0.05)。结论水蛭能有效减轻CSVD所致认知障碍患者的临床症状,改善患者的认知功能障碍。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.
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
文摘Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2015160)
文摘Cerebral small vessel disease(CSVD) is a common etiology of vascular cognitive impairment with no dementia(V-CIND). Studies have revealed that cerebral microbleeds(CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients(29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits(odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall(odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.
文摘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.
文摘Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth Peoples Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).
基金supported by the Austrian Science Funds(P24734-B24)
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the most common form of dementia worldwide.As age is the main risk factor,>97%of all AD cases are of sporadic origin,potentiated by various risk factors associated with life style and starting at an age>60 years.Only<3%of AD cases are of genetic origin caused by mutations in the amyloid precursor protein or Presenilins 1 or 2,and symptoms already start at an age<30 years.In order to study progression of AD,as well as therapeutic strategies,mouse models are state-of-the-art.So far many transgenic mouse models have been developed and used,with mutations in the APP or presenilin or combinations(3×Tg,5×Tg).However,such transgenic mouse models more likely mimic the genetic form of AD and no information can be given how sporadic forms develop.Several risk genes,such as Apolipoprotein E4 and TREM-2 enhance the risk of sporadic AD,but also many risk factors associated with life style(e.g.,diabetes,hypercholesterolemia,stress)may play a role.In this review we discuss the current situation regarding AD mouse models,and the problems to develop a sporadic mouse model of AD.
文摘目的 探讨脑小血管病(CSVD)患者近期皮质下小梗死与认知功能的相关性。方法 回顾性连续纳入2018年2月―2022年9月就诊于北京大学第一医院神经内科经头部MRI诊断的CSVD患者,收集一般人口学资料和临床资料,使用简易精神状态量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,根据磁共振DWI分为近期皮质下小梗死(RSSI)组和非RSSI组,统计RSSI的部位和数目。比较两组患者的一般人口学资料、临床资料、认知功能,分析RSSI影像学特征与认知功能的关系。结果 共纳入CSVD患者181例,RSSI组91例,非RSSI组90例。RSSI组与非RSSI组相比,BMI高[(25.43±3.53)kg/m^(2) vs(24.27±3.33)kg/m^(2),t=2.228, P=0.027],收缩压高[(145.3±16.2)mmHg vs(139.6±20.2)mmHg,t=2.013,P=0.046],MoCA总分较低[22(18.8,26) vs 24(21,27),Z=-1.980,P=0.048],视空间与执行能力[3(2,4) vs 4(3,5),Z=-2.756,P=0.006]、语言[2(2,3) vs 2(1,2), Z=-2.020,P=0.043]、抽象[2(1,2) vs 2(1,2)分,Z=-2.052,P=0.04]得分均较低,差异均具有显著性统计学意义(P<0.05)。RSSI基底节梗死组与非RSSI组相比,MoCA总分较低[21(17,23) vs 24(21,27),Z=-2.018,P=0.044],视空间与执行[3(1.5,3.5) vs 4(3,5),Z=-2.601,P=0.009]得分较低,RSSI脑干梗死组与非RSSI组相比,视空间与执行[3(2,4) vs 4(3,5),Z=-2.325,P=0.020]、语言[2(1,2) vs 2(2,3),Z=-2.338,P=0.019]得分较低,差异具有显著性统计学意义。结论 CSVD患者中RSSI可导致认知功能障碍,与RSSI梗死部位相关,RSSI不同梗死部位导致不同的认知损害模式。预防RSSI发生,对于预防CSVD相关认知功能障碍具有重要意义。