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1、,VCI的诊治新进展,章军建 刘汉兴 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,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,VCI的发展历史,1899年,1969年,1974年,动脉硬化性和老年性痴呆 被认为是不同的综合征,Mayer-Gross描述血管性痴呆(VaD) 以便于与老年性精神病相鉴别,Hachinski 等提出多发梗死性
2、痴呆（MID) 和Hachinski缺血量表(HIS),1985年,Loeb 提出适用广泛的VaD概念,1993年,1997年,Petersen提出VCI新概念,Bowler和Hachinski提出血管性认知功能 损害(VCI),又称血管性认知功能障碍,2011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.,AHA/ASA联合声明-VaD的诊断,The diagnosis of dementia should
3、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 subjects activities of daily living. The diagnosis of dementia must be based on cognitive testing, and a minimum of 4 cognitive domains
4、should be assessed: executive/attention, memory, language, and visuospatial functions.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-VaD的诊断,The deficits in activities of daily living are independent of the motor/sensory sequelae of the vascular event.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-很可能VaD的诊断,Th
5、ere 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 cognitive deficits, or b. There is a clear relationship in the severity and pattern of cognitive impairment and the pr
6、esence of diffuse, subcortical cerebrovascular disease pathology (eg, as in CADASIL). There is no history of gradually progressive cognitive deficits before or after the stroke that suggests the presence of a nonvascular neurodegenerative disorder.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-可能VaD的诊断,T
7、here 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, silent infarcts, subcortical small-vessel disease) and the cognitive impairment. 2. There is insufficient in
8、formation 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. However, patients with documented evidence of normal cognitive function (eg, annual cognitive evalua
9、tions) before the clinical event that caused aphasia could be classified as having probable VaD.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-可能VaD的诊断,There is cognitive impairment and imaging evidence of cerebrovascular disease but 4. There is evidence of other neurodegenerative diseases or conditions
10、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 presence of Alzheimer disease biology is confirmed by biomarkers (eg, PET, CSF, amylo
11、id 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.,AHA/ASA联合声明-VaMCI的诊断,VaMCI includes the 4 subtypes proposed for the classification of MCI: amnestic, amnestic plu
12、s other domains, nonamnestic single domain, and nonamnestic multiple domain. The classification of VaMCI must be based on cognitive testing, and a minimum of 4 cognitive domains should be assessed: executive/attention, memory, language, and visuospatial functions.,VaMCI, vascular mild cognitive impa
13、irment.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-VaMCI的诊断,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. Instrumental activities of daily living could be normal or mildly impaired, independent
14、of the presence of motor/sensory symptoms.,Stroke, 2011;42(9):2672-713.,AHA/ASA联合声明-Unstable VaMCI,Subjects with the diagnosis of probable or possible VaMCI whose symptoms revert to normal should be classified as having “unstable VaMCI.”,Stroke, 2011;42(9):2672-713.,VCI概念简单，组成广泛,VCI 的组成,轻度认知功能损害（MCI
15、）患者,所有脑血管疾病相关的认知损害,所有已知的VaD类型和混合型痴呆,最常见的认知功能损害类型，患病率超过AD,VCI诊断核心要素,认知损害,血管因素,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，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,中华神经科杂志.2011;44(2):142-147.,VCI的诊治新进展,VCI的定义/诊断
16、标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,VCI的神经心理学评估,对VCI的神经心理学评估需要一套综合认知测验。 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脑血管病。 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。,VCI神经心理学评估方案,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.,VCI神经心理学评估方案,Executive/Activation
17、 Animal Naming (semantic fluency); Controlled Oral Word Association Test; WAIS-III Digit Symbol-Coding; Trailmaking Test List Learning Test Strategies Future Use: Simple and Choice Reaction Time Language/Lexical Retrieval Boston Naming Test 2nd Edition, Short Form Visuospatial Rey-Osterrieth Complex
18、 Figure Copy Supplemental: Complex Figure Memory,60分钟方案,Stroke. 2006 Sep;37(9):2220-41.,VCI神经心理学评估方案,60分钟方案,Memory Hopkins Verbal Learning Test-Revised Alternate: California Verbal Learning Test2 Supplemental: Boston Naming Test Recognition Supplemental: Digit Symbol- Coding Incidental Learning Neur
19、opsychiatric/Depressive Symptoms Neuropsychiatric Inventory Questionnaire Version Center for Epidemiological Studies-Depression Scale Premorbid Status Informant Questionnaire for Cognitive Decline in the Elderly, Short Form; MMSE,Stroke. 2006 Sep;37(9):2220-41.,VCI神经心理学评估方案,30分钟方案,Semantic Fluency (
20、Animal Naming) Phonemic Fluency (Controlled Oral Word Association Test) Digit Symbol-Coding from the Wechsler Adult Intelligence Scale, Third Edition Hopkins Verbal Learning Test Center for Epidemiologic Studies-Depression Scale Neuropsychiatric Inventory, Questionnaire Version (NPI-Q) Supplemental:
21、 MMSE, Trail Making Test,Stroke. 2006 Sep;37(9):2220-41.,VCI神经心理学评估方案,5分钟方案,MoCA subtests (MoCA分测验) 5-Word Memory Task (registration, recall, recognition) 6-Item Orientation 1-Letter Phonemic Fluency,Stroke. 2006 Sep;37(9):2220-41.,MoCA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
22、轻微的认知损害”,MoCA-MCI的筛查,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。 筛查有轻度认知功能缺损主诉，但MMSE在正常范围的病人。 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。 执行功能、高水平语言能力和复杂的视觉空间处理方面在MoCA中均得到采用，其数量比MMSE更多，任务要求比MMSE更高些。,筛查TIA/卒中后轻度认知损害，MoCA灵敏度优于MMSE,The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neuro
23、logical Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Battery 1 year after transient ischemic attack and stroke, whereas the MMSE showed a ceiling effect.,2012stroke杂志新研究 样本：91例TIA/卒中后患者，女性44% 平均年龄： 73.4岁,Stroke.2012;43:464-469.,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊
24、断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,VCI的病因分类,危险因素相关性VCI 缺血性VCI 大血管性 小血管性 低灌注性 出血性VCI 其他脑血管病性VCI 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.2011;44(2):142-147.,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
25、 elderly 小血管病在脑血管病中有重要作用，而且是老年人认知功能损害和功能丧失的首要原因，应该做为预防和治疗战略的主要目标,脑小血管病的病因,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 散发性或遗传性脑淀粉样变 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） 炎症或免疫因素介导脑小血管病 静脉胶原病 其他小血管病（放射性血管炎等）,Lancet Neurol 2010, 9, 689-701.,名词的混乱阻碍了SVD的研究,Lancet Neurol 2
26、013; 12: 822838,脑小血管病的影像学分类,新发皮层下小梗死-Recent small subcortical infarct 腔隙-Lacune of presumed vascular origin 血管周围间隙-Perivascular space 脑白质高信号-White matter hyperintensity of presumed vascular origin 脑微出血-Cerebral microbleed 脑萎缩-Brain atrophy,Lancet Neurol 2013; 12: 822838,新发皮层下小梗死,Recent small subcort
27、ical 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发生。,Lancet Neurol 2013; 12: 822838,腔隙,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,腔隙的影像学诊断标准,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
28、%)，放射冠及皮层下白质（含内囊前、后肢、胼胝体）(22%)，小脑(1.6%)。 病灶的信号： 全部序列上均为CSF信号。 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,腔隙的影像学诊断标准,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
29、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,腔隙,腔隙,血管周围间隙,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,血管周围间隙的影像学诊断标准,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。 病灶的大小： 绝大多数2mm；65岁以上社区
30、老年人头颅MRI研究发现，33.2%至少有一个大于3mm的dVRS。 病灶的部位： 基底节区（前穿质）、皮层下白质和脑干。,Lancet Neurol 2013; 12: 822838,血管周围间隙的影像学诊断标准,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,血管周围间隙,脑白质高信号,White matter hyperintensity of pres
31、umed 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）,Lancet Neurol 2013; 12: 822838,脑白质高信号的影像学诊断,脑白质内长T1、T2异常信号，FLAIR图像上呈高信号 两个特征变量 位置：脑室旁、深部等 量（严重程度）：定量、半定量,脑白质高信号的影像学诊断,分级方法 Fazekas scale Rotterdam Scan Study (RSS) scale Scheltens scale 目前尚无统一的标准 Fazekas scale最简单实用,脑白质高信号的影像学诊断,Fazeka
32、s scale Periventricular hyperintensity (PVH) 0=absence 1=caps or 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 areas,Franz Fazekas, AJR, 1987;149
33、:351-356,脑白质高信号的影像学诊断,Fazekas scale-PVH,Grade 1: Pencil-thin line of hyperintensity surrounds ventricles Grade 2: Smooth hale of hyperintensity surrounds ventricles Grade 3: Diffuse irregular PVH extending into DWH,Franz Fazekas, AJR, 1987;149:351-356,脑白质高信号的影像学诊断,Fazekas scale-DWMH Grade 1,脑白质高信号的影
34、像学诊断,Fazekas scale-DWMH Grade 2,脑白质高信号的影像学诊断,Fazekas scale-DWMH Grade 1,脑微出血,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。,脑微出血,脑微出血的影像学诊断,Recommended criteria for identifi cation of cereb
35、ral microbleeds Black lesions on T2*-weighted MRI Round or ovoid 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 a
36、s iron or calcium deposits, bone, or vessel flow voids Clinical history excluding traumatic diffuse axonal injury,Lancet Neurol 2009; 8: 16574,脑微出血,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%） 高血压与淀粉样脑血管病微出血部位不同,脑萎缩,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
37、,不同脑小血管病的影像区别,Lancet Neurol 2013; 12: 822838,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,与VaD相关的脑影像学损害,Large-vessel strokes in the following territories Bilateral ACA PCA, including paramedian thalamic infarcts, inferior medial temporal lobe lesions MCA, including parieto
38、temporal, temporooccipital territories, and/or angular gyrus Watershed carotid territories: bilateral superior frontal, parieto-occipital and/or deep and superficial MCA,Neuroradiology. 2007;49(1):1-22.,与VaD相关的脑影像学损害,Small-vessel disease: Multiple basal ganglia and frontal white matter lacunae (must
39、 be two or more lacunae in the basal ganglia and two or more lacunae in the frontal white matter) Extensive periventricular white matter lesions (as defined in IIC) Bilateral thalamic lesions,Neuroradiology. 2007;49(1):1-22.,与VaD相关的脑影像学损害,Severity-In addition to the above, relevant radiological lesi
40、ons associated with dementia include Large-vessel lesions of the dominant 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),Neu
41、roradiology. 2007;49(1):1-22.,Angular gyrus infarct,Fig. 1 Angular gyrus infarct 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 hyperintensities,Neuroradiolo
42、gy. 2007;49(1):1-22.,Thalamic infarct,Fig. 2 Thalamic infarct in a 58-year-old man 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-w
43、eighted MR image confirms the thalamic infarct and the cerebral atrophy. It also shows mild bilateral hippocampal atrophy. The white matter abnormalities are difficult to see as periventricular hypointensities (arrows),Neuroradiology. 2007;49(1):1-22.,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定
44、影像学与认知损害的关系 VCI的治疗进展 小结,VCI的治疗,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,血管危险因素/脑血管病变是VCI的起始环节,危险因素 首要病理学 血管改变 终末期结果 中间因素 后果,认知功能损害,高血压,糖尿病,吸烟,高脂血症,炎症,动脉粥样硬化,动脉僵硬度,内皮损伤,小血管病 血管/管腔狭窄 心功能不全,腔隙性梗死 关键部位梗死 慢性低灌注,自主调节损伤 高白质信号,基因(ApoE, Notch3),AD病理学,Stroke. 2011;42:221-2
45、26.,VCI的危险因素控制推荐,In people at risk for VCI, smoking cessation is reasonable (Class IIa; Level of Evidence A). 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; Level of Evidenc
46、e B); and physical activity (Class IIb; Level of Evidence B). 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 Factors,Stroke, 2011;42(9):2672-713.,VCI的危险因素控制推荐,In people at risk for VCI, tre
47、atment of hypertension is recommended (Class I; Level of Evidence A). In people at risk for VCI, treatment of hyperglycemia may be reasonable (Class IIb; Level of Evidence C). In people at risk for VCI, treatment of hypercholesterolemia may be reasonable (Class IIb; Level of Evidence B). In people a
48、t risk for VCI, it is uncertain whether treatment of inflammation will reduce such risk (Class IIb; Level of Evidence C).,Physiological Risk Factors,Stroke, 2011;42(9):2672-713.,VaD患者脑脊液中Ach显著下降,r=0.62, P0.02 in VD,J Neural Transm, 1996;103:1211-1220,VCI药物治疗的推荐,Stroke, 2011;42(9):2672-713.,VCI的诊治新进展,VCI的定义/诊断标准 VCI的神经心理学评估 VCI的影像学诊断 如何确定影像学与认知损害的关系 VCI的治疗进展 小结,小结,VCI的定义 VCI诊断核心要素：认知损害、影像学、两者有因果关系 VCI的神经心理学评估：MoCA量表 SVD的影像学诊断 VaD的放射学诊断 VCI的治疗：危险因素控制、症状治疗,Thank you very much!,