1、VCI的诊治新进展章军建章军建 刘汉兴刘汉兴武汉大学中南医院神经科武汉大学中南医院神经科湖北省痴呆与认知障碍医学临床研究中心湖北省痴呆与认知障碍医学临床研究中心 2VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 3VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 4VCI的发展历史1899年年1969年年1974年年动脉硬化性和老年性痴呆动脉硬化性和老年性痴呆被认为是不同的综合征被认
2、为是不同的综合征Mayer-Gross描述血管性痴呆描述血管性痴呆(VaD)以便于与老年性精神病相鉴别以便于与老年性精神病相鉴别Hachinski 等提出多发梗死性痴呆（等提出多发梗死性痴呆（MID)和和Hachinski缺血量表缺血量表(HIS)1985年年Loeb 提出适用广泛的提出适用广泛的VaD概念概念1993年年1997年年Petersen提出提出VCI新概念新概念Bowler和和Hachinski提出血管性认知功能提出血管性认知功能损害损害(VCI),又称血管性认知功能障碍又称血管性认知功能障碍 52011年7月AHA/ASA联合发表科学声明-专门针对VCI定义：VCI指存在临床卒
3、中或亚临床脑血管损伤，引起至少一个认知功能区认知功能受损的一组综合征，其中最严重的形式为VaD。Stroke,2011;42(9):2672-713.6AHA/ASA联合声明-VaD的诊断n The diagnosis of dementia should be based on a decline in cognitive function from a prior baseline and a deficit in performance in 2 cognitive domains that are of sufficient severity to affect the subject
4、s activities of daily living.n The diagnosis of dementia must be based on cognitive testing,and a minimum of 4 cognitive domains should be assessed:executive/attention,memory,language,and visuospatial functions.Stroke,2011;42(9):2672-713.7AHA/ASA联合声明-VaD的诊断n The deficits in activities of daily livin
5、g are independent of the motor/sensory sequelae of the vascular event.Stroke,2011;42(9):2672-713.8AHA/ASA联合声明-很可能VaD的诊断n There is cognitive impairment and imaging evidence of cerebrovascular disease and a.There is a clear temporal relationship between a vascular event(eg,clinical stroke)and onset of
6、 cognitive deficits,or b.There is a clear relationship in the severity and pattern of cognitive impairment and the presence of diffuse,subcortical cerebrovascular disease pathology(eg,as in CADASIL).n There is no history of gradually progressive cognitive deficits before or after the stroke that sug
7、gests the presence of a nonvascular neurodegenerative disorder.Stroke,2011;42(9):2672-713.9AHA/ASA联合声明-可能VaD的诊断n There is cognitive impairment and imaging evidence of cerebrovascular disease but 1.There is no clear relationship(temporal,severity,or cognitive pattern)between the vascular disease(eg,s
8、ilent infarcts,subcortical small-vessel disease)and the cognitive impairment.2.There is insufficient information for the diagnosis of VaD(eg,clinical symptoms suggest the presence of vascular disease,but no CT/MRI studies are available).3.Severity of aphasia precludes proper cognitive assessment.How
9、ever,patients with documented evidence of normal cognitive function(eg,annual cognitive evaluations)before the clinical event that caused aphasia could be classified as having probable VaD.Stroke,2011;42(9):2672-713.10AHA/ASA联合声明-可能VaD的诊断n There is cognitive impairment and imaging evidence of cerebr
10、ovascular disease but 4.There is evidence of other neurodegenerative diseases or conditions in addition to cerebrovascular disease that may affect cognition,such as a.A history of other neurodegenerative disorders(eg,Parkinson disease,progressive supranuclear palsy,dementia with Lewy bodies);b.The p
11、resence of Alzheimer disease biology is confirmed by biomarkers(eg,PET,CSF,amyloid ligands)or genetic studies(eg,PS1 mutation);or c.A history of active cancer or psychiatric or metabolic disorders that may affect cognitive function.Stroke,2011;42(9):2672-713.11AHA/ASA联合声明-VaMCI的诊断n VaMCI includes th
12、e 4 subtypes proposed for the classification of MCI:amnestic,amnestic plus other domains,nonamnestic single domain,and nonamnestic multiple domain.n The classification of VaMCI must be based on cognitive testing,and a minimum of 4 cognitive domains should be assessed:executive/attention,memory,langu
13、age,and visuospatial functions.VaMCI,vascular mild cognitive impairment.Stroke,2011;42(9):2672-713.12AHA/ASA联合声明-VaMCI的诊断n The classification should be based on an assumption of decline in cognitive function from a prior baseline and impairment in at least 1 cognitive domain.n Instrumental activitie
14、s of daily living could be normal or mildly impaired,independent of the presence of motor/sensory symptoms.Stroke,2011;42(9):2672-713.13AHA/ASA联合声明-Unstable VaMCIn Subjects with the diagnosis of probable or possible VaMCI whose symptoms revert to normal should be classified as having“unstable VaMCI.
15、”Stroke,2011;42(9):2672-713.14VCI概念简单，组成广泛VCI 的组成的组成轻度认知功能损害轻度认知功能损害（MCI）患者）患者所有脑血管疾病所有脑血管疾病相关的认知损害相关的认知损害所有已知的所有已知的VaD类类型和混合型痴呆型和混合型痴呆最常见的认知功最常见的认知功能损害类型，患能损害类型，患病率超过病率超过AD 15VCI诊断核心要素认知损害认知损害血管因素血管因素两者有因果关系两者有因果关系主诉或知情者报告有认知损害，而且客观检查也有认知损害的证据，和(或)客观检查证实认知功能较以往减退包括血管危险因素、卒中病史、神经系统局灶体征、影像学显示的脑血管病证据，
16、以上各项不一定同时具备通过病史、体格检查、实验室和影像学检查确定认知损害与血管因素有因果关系，并能排除其他原因应用合适的诊断工具筛查认知功能损害，确定核心要素应用合适的诊断工具筛查认知功能损害，确定核心要素中华神经科杂志.2011;44(2):142-147.16VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 17VCI的神经心理学评估n 对VCI的神经心理学评估需要一套综合认知测验。n 执行功能早已被认为是VCI患者的突出特征，故应包含在神经心理成套测验中。但执行功能障碍并非特别地指向
17、脑血管病。n 对认知损害的操作性定义（如低于类似人群的1个或1.5个标准差）优于对症状的定性描述。18VCI神经心理学评估方案n NINDS-CSN推荐方案 60分钟方案 30分钟方案 5分钟方案Stroke.2006 Sep;37(9):2220-41.19VCI神经心理学评估方案n Executive/Activation Animal Naming(semantic fluency);Controlled Oral Word Association Test;WAIS-III Digit Symbol-Coding;Trailmaking Test List Learning Test
18、Strategies Future Use:Simple and Choice Reaction Timen Language/Lexical Retrieval Boston Naming Test 2nd Edition,Short Formn Visuospatial Rey-Osterrieth Complex Figure Copy Supplemental:Complex Figure Memory 60分钟方案Stroke.2006 Sep;37(9):2220-41.20VCI神经心理学评估方案 60分钟方案n Memory Hopkins Verbal Learning Te
19、st-Revised Alternate:California Verbal Learning Test2 Supplemental:Boston Naming Test Recognition Supplemental:Digit Symbol-Coding Incidental Learningn Neuropsychiatric/Depressive Symptoms Neuropsychiatric Inventory Questionnaire Version Center for Epidemiological Studies-Depression Scalen Premorbid
20、 Status Informant Questionnaire for Cognitive Decline in the Elderly,Short Form;MMSEStroke.2006 Sep;37(9):2220-41.21VCI神经心理学评估方案 30分钟方案n Semantic Fluency(Animal Naming)n Phonemic Fluency(Controlled Oral Word Association Test)n Digit Symbol-Coding from the Wechsler Adult Intelligence Scale,Third Edit
21、ionn Hopkins Verbal Learning Testn Center for Epidemiologic Studies-Depression Scalen Neuropsychiatric Inventory,Questionnaire Version(NPI-Q)n Supplemental:MMSE,Trail Making TestStroke.2006 Sep;37(9):2220-41.22VCI神经心理学评估方案 5分钟方案n MoCA subtests(MoCA分测验)5-Word Memory Task(registration,recall,recogniti
22、on)6-Item Orientation 1-Letter Phonemic FluencyStroke.2006 Sep;37(9):2220-41.23MoCA已在中国广泛使用2011年中国血管性认知障碍诊治指南“蒙特利尔认知量表(MoCA)已在中国广泛使用，显示出比MMSE更能识别轻微的认知损害”24MoCA-MCI的筛查n 简短的认知功能筛查，帮助医生早期发现轻度认知障碍（MCI）患者。n 筛查有轻度认知功能缺损主诉，但MMSE在正常范围的病人。n 与MMSE相比，MoCA记忆测试用的词较多，学习试验较少，回忆前的延迟较长。n 执行功能、高水平语言能力和复杂的视觉空间处理方面在MoC
23、A中均得到采用，其数量比MMSE更多，任务要求比MMSE更高些。25筛查TIA/卒中后轻度认知损害，MoCA灵敏度优于MMSEn The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Battery 1 year after transient ischemic attack and stroke,whereas
24、 the MMSE showed a ceiling effect.2012stroke杂志新研究n样本：91例TIA/卒中后患者，女性44%n平均年龄：73.4岁Stroke.2012;43:464-469.26VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 27VCI的病因分类n 危险因素相关性VCIn 缺血性VCI 大血管性 小血管性 低灌注性n 出血性VCIn 其他脑血管病性VCIn 脑血管病合并AD 脑血管病伴AD AD伴脑血管病中华神经科杂志中华神经科杂志.2011;44(2
25、):142-147.28脑小血管病变在VCI中的重要作用 Small vessel disease has an important role in cerebrovascular disease and is a leading cause of cognitive decline and functional loss in the elderly 小血管病在脑血管病中有小血管病在脑血管病中有重要作用重要作用，而且是老年人认知功能，而且是老年人认知功能损害和功能丧失的损害和功能丧失的首要原因首要原因，应该做为预防和治疗战略的主，应该做为预防和治疗战略的主要目标要目标 29脑小血管病的病因n
26、 动脉硬化性(年龄和血管病危险因素相关的脑小血管病）脂肪玻璃样变、玻璃样变、纤维素样坏死、微动脉瘤、小动脉硬化n 散发性或遗传性脑淀粉样变n 非淀粉样变的遗传性脑小血管病（CADASIL、CARASIL、遗传性视网膜血管病伴脑白质病、COL4A1小血管病）n 炎症或免疫因素介导脑小血管病n 静脉胶原病n 其他小血管病（放射性血管炎等）Lancet Neurol 2010,9,689-701.30名词的混乱阻碍了SVD的研究Lancet Neurol 2013;12:822838 31脑小血管病的影像学分类n 新发皮层下小梗死-Recent small subcortical infarctn
27、腔隙-Lacune of presumed vascular originn 血管周围间隙-Perivascular space n 脑白质高信号-White matter hyperintensity of presumed vascular origin n 脑微出血-Cerebral microbleed n 脑萎缩-Brain atrophy Lancet Neurol 2013;12:822838 32新发皮层下小梗死n Recent small subcortical infarct新发皮层下小梗死 影像发现近期位于穿动脉分布区的小梗死（20mm），影像或临床症状提示病变于过去数周
28、发生。Lancet Neurol 2013;12:822838 33腔隙n Lacune of presumed vascular origin 3-15mm直径的，圆形或卵圆形，皮层下，充满液体的小洞（信号接近脑脊液信号），源于既往的穿动脉分布区急性皮层下小梗死或出血。Lancet Neurol 2013;12:822838 34腔隙的影像学诊断标准n 病灶的部位：基底节区、脑白质和桥脑。最好发的部位分别为豆状核(37%)，桥脑(16%)，丘脑(14%)，尾状核(10%)，放射冠及皮层下白质（含内囊前、后肢、胼胝体）(22%)，小脑(1.6%)。n 病灶的信号：全部序列上均为CSF信号。n
29、病灶的大小：3-15mm（病理研究显示，腔隙的长径通常在1-4mm之间，Fisher报道的最大长径为17mm）。Lancet Neurol 2013;12:822838 35腔隙的影像学诊断标准n 除外诊断标准：信号为CSF的病灶需除外扩张的血管周围间隙(dVRS)(1)病灶大小：3mm病灶均被认为是dVRS(2)3mm病灶：a.腔隙病灶周边边界不规整，而dVRS多表现为光滑边界；b.腔隙病灶周围存在胶质增生，在FLAIR上可见病灶周边有高密度信号环绕，而dVRS往往没有；c.应用高分辨率核磁和三维多平面成像技术可以对小空洞形态进行分析。Lancet Neurol 2013;12:822838
30、 36腔隙 37腔隙 38血管周围间隙n Perivascular space 一个充满液体的腔围绕在穿支血管周围，与脑脊液信号相同，在平行于血管走行的平面呈现线样，图像平面垂直于血管时，呈现圆形或卵圆形，直径通常小于3mm。Lancet Neurol 2013;12:822838 39血管周围间隙的影像学诊断标准n 病灶的信号：全部MRI序列上显示为水信号；在FLAIR像上，绝大多数dVRS周边没有高密度的环。n 病灶的大小：绝大多数2mm；65岁以上社区老年人头颅MRI研究发现，33.2%至少有一个大于3mm的dVRS。n 病灶的部位：基底节区（前穿质）、皮层下白质和脑干。Lancet N
31、eurol 2013;12:822838 40血管周围间隙的影像学诊断标准n 病灶的形态：周壁光滑；圆形、卵圆形或线性结构，与检查平面的位置相关；当检查平面与穿动脉平行时，通常表现为类似血管形态的细线样结构，有时也可见到圆形或卵圆形结构带有一个细线血管样的延伸，或两个囊状结构似葫芦状串在一起。Lancet Neurol 2013;12:822838 41血管周围间隙 42脑白质高信号n White matter hyperintensity of presumed vascular origin 脑白质高信号 是指T2上显示为高信号，并且T1上为等信号或低信号（但不与脑脊液信号相同）Lance
32、t Neurol 2013;12:822838 43脑白质高信号的影像学诊断n 脑白质内长T1、T2异常信号，FLAIR图像上呈高信号n 两个特征变量 位置：脑室旁、深部等 量（严重程度）：定量、半定量 44脑白质高信号的影像学诊断n 分级方法 Fazekas scale Rotterdam Scan Study(RSS)scale Scheltens scalen 目前尚无统一的标准n Fazekas scale最简单实用 45脑白质高信号的影像学诊断n Fazekas scale Periventricular hyperintensity(PVH)0=absence 1=caps or
33、pencil-thin lining 2=smooth halo 3=irregular PVH extending into the deep white matter Deep white matter hyperintensity(DWMH)0=absence 1=punctate foci 2=beginning confluence of foci 3=large confluent areasFranz Fazekas,AJR,1987;149:351-356 46脑白质高信号的影像学诊断n Fazekas scale-PVHGrade 1:Pencil-thin line of
34、hyperintensity surrounds ventriclesGrade 2:Smooth hale of hyperintensity surrounds ventriclesGrade 3:Diffuse irregular PVH extending into DWHFranz Fazekas,AJR,1987;149:351-356 47脑白质高信号的影像学诊断n Fazekas scale-DWMH Grade 1 48脑白质高信号的影像学诊断n Fazekas scale-DWMH Grade 2 49脑白质高信号的影像学诊断n Fazekas scale-DWMH Gra
35、de 1 50脑微出血n Cerebral microbleed 脑微出血是一种亚临床的终末期微小血管病变导致的含铁血黄素沉积。1996年Offenbancher首次提出，GRE-T2*序列 在T2*或SWI序列上可见的圆形或卵圆形小灶信号丢失（通常直径在2-5mm，也可大至10mm），病灶在CT、FLAIR、T1和T2序列上均不可见。51脑微出血 52脑微出血的影像学诊断n Recommended criteria for identifi cation of cerebral microbleeds Black lesions on T2*-weighted MRI Round or ov
36、oid lesions(rather than linear)Blooming effect on T2*-weighted MRI Devoid of signal hyperintensity on T1-weighted or T2-weighted sequences At least half of lesion surrounded by brain parenchyma Distinct from other potential mimics such as iron or calcium deposits,bone,or vessel flow voids Clinical h
37、istory excluding traumatic diffuse axonal injuryLancet Neurol 2009;8:16574 53脑微出血n 脑微出血的好发部位：皮质及皮质下（50.7%）、基底节及丘脑（34.1%）脑干（9.0%）、小脑（6.2%）n 高血压与淀粉样脑血管病微出血部位不同 54脑萎缩n Brain atrophy 与肉眼可见的局灶损伤如外伤和梗死不相关的脑容量的减少。Lancet Neurol 2013;12:822838 55不同脑小血管病的影像区别Lancet Neurol 2013;12:822838 56VCI的诊治新进展n VCI的定义/诊断
38、标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 57与VaD相关的脑影像学损害n Large-vessel strokes in the following territories Bilateral ACA PCA,including paramedian thalamic infarcts,inferior medial temporal lobe lesions MCA,including parietotemporal,temporooccipital territories,and/or angular gyrus
39、Watershed carotid territories:bilateral superior frontal,parieto-occipital and/or deep and superficial MCANeuroradiology.2007;49(1):1-22.58与VaD相关的脑影像学损害n Small-vessel disease:Multiple basal ganglia and frontal white matter lacunae(must be two or more lacunae in the basal ganglia and two or more lacu
40、nae in the frontal white matter)Extensive periventricular white matter lesions(as defined in IIC)Bilateral thalamic lesionsNeuroradiology.2007;49(1):1-22.59与VaD相关的脑影像学损害n Severity-In addition to the above,relevant radiological lesions associated with dementia include Large-vessel lesions of the domi
41、nant hemisphere Bilateral large-vessel hemispheric strokes Leukoencephalopathy involving at least 25%of the total white matter(beginning to become confluent in four regions,i.e.,frontal bilaterally and parietal bilaterally)Neuroradiology.2007;49(1):1-22.60Angular gyrus infarctFig.1 Angular gyrus inf
42、arct in a 63-year-old woman with cognitive impairment.a Axial and b coronal FLAIR MR images show infarct in the left dominant angular gyrus.There are also periventricular and deep white matter hyperintensitiesNeuroradiology.2007;49(1):1-22.61Thalamic infarctFig.2 Thalamic infarct in a 58-year-old ma
43、n with dementia.a Axial FLAIR MR image shows infarct in the left dominant thalamus(arrow).There are also periventricular and deep white matter hyperintensities and global mild cerebral atrophy.b Coronal 3D SPGR T1-weighted MR image confirms the thalamic infarct and the cerebral atrophy.It also shows
44、 mild bilateral hippocampal atrophy.The white matter abnormalities are difficult to see as periventricular hypointensities(arrows)Neuroradiology.2007;49(1):1-22.62VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 63VCI的治疗n VCI治疗首先应给于病因治疗。出现症状时可给于对症治疗药物 针对血管因素以防治卒中的治疗 特异针对
45、提高认知水平的药物治疗 加强康复训练、积极开展非药物治疗 64血管危险因素/脑血管病变是VCI的起始环节危险因素危险因素首要病理学首要病理学血管改变血管改变终末期结果终末期结果中间因素中间因素后果后果认知功能损害高血压高血压,糖尿病糖尿病,吸烟吸烟,高脂血症高脂血症,炎症炎症动脉粥样硬化动脉粥样硬化,动脉僵硬度动脉僵硬度,内皮损伤内皮损伤小血管病小血管病 血管血管/管腔狭窄管腔狭窄 心功能不全心功能不全腔隙性梗死腔隙性梗死 关键部位梗死关键部位梗死 慢性低灌注慢性低灌注自主调节损伤自主调节损伤 高白质信号高白质信号基因基因(ApoE,(ApoE,Notch3)Notch3)ADAD病理学病理学
46、Stroke.2011;42:221-226.65VCI的危险因素控制推荐n In people at risk for VCI,smoking cessation is reasonable(Class IIa;Level of Evidence A).n In people at risk for VCI,the following lifestyle interventions may be reasonable:moderation of alcohol intake(Class IIb;Level of Evidence B);weight control(Class IIb;Lev
47、el of Evidence B);and physical activity(Class IIb;Level of Evidence B).n 3.In people at risk for VCI,the use of antioxidants and B vitamins is not beneficial,based on current evidence(Class III;Level of Evidence A).Lifestyle FactorsStroke,2011;42(9):2672-713.66VCI的危险因素控制推荐n In people at risk for VCI
48、,treatment of hypertension is recommended(Class I;Level of Evidence A).n In people at risk for VCI,treatment of hyperglycemia may be reasonable(Class IIb;Level of Evidence C).n In people at risk for VCI,treatment of hypercholesterolemia may be reasonable(Class IIb;Level of Evidence B).n In people at
49、 risk for VCI,it is uncertain whether treatment of inflammation will reduce such risk(Class IIb;Level of Evidence C).Physiological Risk FactorsStroke,2011;42(9):2672-713.67VaD患者脑脊液中Ach显著下降r=0.62,P0.02 in VDJ Neural Transm,1996;103:1211-1220 68VCI药物治疗的推荐Stroke,2011;42(9):2672-713.69VCI的诊治新进展n VCI的定义/诊断标准n VCI的神经心理学评估n VCI的影像学诊断n 如何确定影像学与认知损害的关系n VCI的治疗进展n 小结 70小结n VCI的定义n VCI诊断核心要素：认知损害、影像学、两者有因果关系n VCI的神经心理学评估：MoCA量表n SVD的影像学诊断n VaD的放射学诊断n VCI的治疗：危险因素控制、症状治疗Thank you very much!
