血管性認(rèn)知障礙的診治新進(jìn)展

1、,VCI的診治新進(jìn)展,章軍建 劉漢興 武漢大學(xué)中南醫(yī)院神經(jīng)科 湖北省癡呆與認(rèn)知障礙醫(yī)學(xué)臨床研究中心,VCI的診治新進(jìn)展,VCI的定義/診斷標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),VCI的診治新進(jìn)展,VCI的定義/診斷標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),VCI的發(fā)展歷史,1899年,1969年,1974年,動(dòng)脈硬化性和老年性癡呆 被認(rèn)為是不同的綜合征,Mayer-Gross描述血管性癡呆(VaD) 以便于與老年性精神病相鑒別,Hachinski 等提出多發(fā)梗死性

2、癡呆（MID) 和Hachinski缺血量表(HIS),1985年,Loeb 提出適用廣泛的VaD概念,1993年,1997年,Petersen提出VCI新概念,Bowler和Hachinski提出血管性認(rèn)知功能 損害(VCI),又稱血管性認(rèn)知功能障礙,2011年7月AHA/ASA聯(lián)合發(fā)表科學(xué)聲明-專門針對(duì)VCI,定義：VCI指存在臨床卒中或亞臨床腦血管損傷，引起至少一個(gè)認(rèn)知功能區(qū)認(rèn)知功能受損的一組綜合征，其中最嚴(yán)重的形式為VaD。,Stroke, 2011;42(9):2672-713.,AHA/ASA聯(lián)合聲明-VaD的診斷,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聯(lián)合聲明-VaD的診斷,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聯(lián)合聲明-很可能VaD的診斷,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聯(lián)合聲明-可能VaD的診斷,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聯(lián)合聲明-可能VaD的診斷,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聯(lián)合聲明-VaMCI的診斷,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聯(lián)合聲明-VaMCI的診斷,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聯(lián)合聲明-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概念簡單，組成廣泛,VCI 的組成,輕度認(rèn)知功能損害（MCI

15、）患者,所有腦血管疾病相關(guān)的認(rèn)知損害,所有已知的VaD類型和混合型癡呆,最常見的認(rèn)知功能損害類型，患病率超過AD,VCI診斷核心要素,認(rèn)知損害,血管因素,兩者有因果關(guān)系,主訴或知情者報(bào)告有認(rèn)知損害，而且客觀檢查也有認(rèn)知損害的證據(jù)，和(或)客觀檢查證實(shí)認(rèn)知功能較以往減退,包括血管危險(xiǎn)因素、卒中病史、神經(jīng)系統(tǒng)局灶體征、影像學(xué)顯示的腦血管病證據(jù)，以上各項(xiàng)不一定同時(shí)具備,通過病史、體格檢查、實(shí)驗(yàn)室和影像學(xué)檢查確定認(rèn)知損害與血管因素有因果關(guān)系，并能排除其他原因,應(yīng)用合適的診斷工具篩查認(rèn)知功能損害，確定核心要素,中華神經(jīng)科雜志.2011;44(2):142-147.,VCI的診治新進(jìn)展,VCI的定義/診斷

16、標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),VCI的神經(jīng)心理學(xué)評(píng)估,對(duì)VCI的神經(jīng)心理學(xué)評(píng)估需要一套綜合認(rèn)知測(cè)驗(yàn)。 執(zhí)行功能早已被認(rèn)為是VCI患者的突出特征，故應(yīng)包含在神經(jīng)心理成套測(cè)驗(yàn)中。但執(zhí)行功能障礙并非特別地指向腦血管病。 對(duì)認(rèn)知損害的操作性定義（如低于類似人群的1個(gè)或1.5個(gè)標(biāo)準(zhǔn)差）優(yōu)于對(duì)癥狀的定性描述。,VCI神經(jīng)心理學(xué)評(píng)估方案,NINDS-CSN推薦方案 60分鐘方案 30分鐘方案 5分鐘方案,Stroke. 2006 Sep;37(9):2220-41.,VCI神經(jīng)心理學(xué)評(píng)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分鐘方案,Stroke. 2006 Sep;37(9):2220-41.,VCI神經(jīng)心理學(xué)評(píng)估方案,60分鐘方案,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神經(jīng)心理學(xué)評(píng)估方案,30分鐘方案,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神經(jīng)心理學(xué)評(píng)估方案,5分鐘方案,MoCA subtests (MoCA分測(cè)驗(yàn)) 5-Word Memory Task (registration, recall, recognition) 6-Item Orientation 1-Letter Phonemic Fluency,Stroke. 2006 Sep;37(9):2220-41.,MoCA已在中國廣泛使用,2011年中國血管性認(rèn)知障礙診治指南,“蒙特利爾認(rèn)知量表(MoCA)已在中國廣泛使用，顯示出比MMSE更能識(shí)別

22、輕微的認(rèn)知損害”,MoCA-MCI的篩查,簡短的認(rèn)知功能篩查，幫助醫(yī)生早期發(fā)現(xiàn)輕度認(rèn)知障礙（MCI）患者。 篩查有輕度認(rèn)知功能缺損主訴，但MMSE在正常范圍的病人。 與MMSE相比，MoCA記憶測(cè)試用的詞較多，學(xué)習(xí)試驗(yàn)較少，回憶前的延遲較長。 執(zhí)行功能、高水平語言能力和復(fù)雜的視覺空間處理方面在MoCA中均得到采用，其數(shù)量比MMSE更多，任務(wù)要求比MMSE更高些。,篩查TIA/卒中后輕度認(rèn)知損害，MoCA靈敏度優(yōu)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雜志新研究 樣本：91例TIA/卒中后患者，女性44% 平均年齡： 73.4歲,Stroke.2012;43:464-469.,VCI的診治新進(jìn)展,VCI的定義/診斷標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診

24、斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),VCI的病因分類,危險(xiǎn)因素相關(guān)性VCI 缺血性VCI 大血管性 小血管性 低灌注性 出血性VCI 其他腦血管病性VCI 腦血管病合并AD 腦血管病伴AD AD伴腦血管病,中華神經(jīng)科雜志.2011;44(2):142-147.,腦小血管病變?cè)赩CI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 小血管病在腦血管病中有重要作用，而且是老年人認(rèn)知功能損害和功能喪失的首要原因，應(yīng)該做為預(yù)防和治療戰(zhàn)略的主要目標(biāo),腦小血管病的病因,動(dòng)脈硬化性(年齡和血管病危險(xiǎn)因素相關(guān)的腦小血管?。?脂肪玻璃樣變、玻璃樣變、纖維素樣壞死、微動(dòng)脈瘤、小動(dòng)脈硬化 散發(fā)性或遺傳性腦淀粉樣變 非淀粉樣變的遺傳性腦小血管病（CADASIL、CARASIL、遺傳性視網(wǎng)膜血管病伴腦白質(zhì)病、COL4A1小血管?。?炎癥或免疫因素介導(dǎo)腦小血管病 靜脈膠原病 其他小血管?。ǚ派湫匝苎椎龋?Lancet Neurol 2010, 9, 689-701.,名詞的混亂阻礙了SVD的研究,Lancet Neurol 2

26、013; 12: 822838,腦小血管病的影像學(xué)分類,新發(fā)皮層下小梗死-Recent small subcortical infarct 腔隙-Lacune of presumed vascular origin 血管周圍間隙-Perivascular space 腦白質(zhì)高信號(hào)-White matter hyperintensity of presumed vascular origin 腦微出血-Cerebral microbleed 腦萎縮-Brain atrophy,Lancet Neurol 2013; 12: 822838,新發(fā)皮層下小梗死,Recent small subcort

27、ical infarct新發(fā)皮層下小梗死 影像發(fā)現(xiàn)近期位于穿動(dòng)脈分布區(qū)的小梗死（20mm），影像或臨床癥狀提示病變于過去數(shù)周發(fā)生。,Lancet Neurol 2013; 12: 822838,腔隙,Lacune of presumed vascular origin 3-15mm直徑的，圓形或卵圓形，皮層下，充滿液體的小洞（信號(hào)接近腦脊液信號(hào)），源于既往的穿動(dòng)脈分布區(qū)急性皮層下小梗死或出血。,Lancet Neurol 2013; 12: 822838,腔隙的影像學(xué)診斷標(biāo)準(zhǔn),病灶的部位： 基底節(jié)區(qū)、腦白質(zhì)和橋腦。最好發(fā)的部位分別為豆?fàn)詈?37%)，橋腦(16%)，丘腦(14%)，尾狀核(10

28、%)，放射冠及皮層下白質(zhì)（含內(nèi)囊前、后肢、胼胝體）(22%)，小腦(1.6%)。 病灶的信號(hào)： 全部序列上均為CSF信號(hào)。 病灶的大?。?3-15mm（病理研究顯示，腔隙的長徑通常在1-4mm之間，F(xiàn)isher報(bào)道的最大長徑為17mm）。,Lancet Neurol 2013; 12: 822838,腔隙的影像學(xué)診斷標(biāo)準(zhǔn),除外診斷標(biāo)準(zhǔn)： 信號(hào)為CSF的病灶需除外擴(kuò)張的血管周圍間隙(dVRS) (1)病灶大?。?mm病灶均被認(rèn)為是dVRS (2)3mm病灶： a. 腔隙病灶周邊邊界不規(guī)整，而dVRS多表現(xiàn)為光滑邊界； b. 腔隙病灶周圍存在膠質(zhì)增生，在FLAIR上可見病灶周邊有高密度信號(hào)環(huán)繞，而

29、dVRS往往沒有； c. 應(yīng)用高分辨率核磁和三維多平面成像技術(shù)可以對(duì)小空洞形態(tài)進(jìn)行分析。,Lancet Neurol 2013; 12: 822838,腔隙,腔隙,血管周圍間隙,Perivascular space 一個(gè)充滿液體的腔圍繞在穿支血管周圍，與腦脊液信號(hào)相同，在平行于血管走行的平面呈現(xiàn)線樣，圖像平面垂直于血管時(shí)，呈現(xiàn)圓形或卵圓形，直徑通常小于3mm。,Lancet Neurol 2013; 12: 822838,血管周圍間隙的影像學(xué)診斷標(biāo)準(zhǔn),病灶的信號(hào)： 全部MRI序列上顯示為水信號(hào)；在FLAIR像上，絕大多數(shù)dVRS周邊沒有高密度的環(huán)。 病灶的大?。?絕大多數(shù)2mm；65歲以上社區(qū)

30、老年人頭顱MRI研究發(fā)現(xiàn)，33.2%至少有一個(gè)大于3mm的dVRS。 病灶的部位： 基底節(jié)區(qū)（前穿質(zhì)）、皮層下白質(zhì)和腦干。,Lancet Neurol 2013; 12: 822838,血管周圍間隙的影像學(xué)診斷標(biāo)準(zhǔn),病灶的形態(tài)： 周壁光滑； 圓形、卵圓形或線性結(jié)構(gòu)，與檢查平面的位置相關(guān)； 當(dāng)檢查平面與穿動(dòng)脈平行時(shí)，通常表現(xiàn)為類似血管形態(tài)的細(xì)線樣結(jié)構(gòu)，有時(shí)也可見到圓形或卵圓形結(jié)構(gòu)帶有一個(gè)細(xì)線血管樣的延伸，或兩個(gè)囊狀結(jié)構(gòu)似葫蘆狀串在一起。,Lancet Neurol 2013; 12: 822838,血管周圍間隙,腦白質(zhì)高信號(hào),White matter hyperintensity of pres

31、umed vascular origin 腦白質(zhì)高信號(hào) 是指T2上顯示為高信號(hào)，并且T1上為等信號(hào)或低信號(hào)（但不與腦脊液信號(hào)相同）,Lancet Neurol 2013; 12: 822838,腦白質(zhì)高信號(hào)的影像學(xué)診斷,腦白質(zhì)內(nèi)長T1、T2異常信號(hào)，F(xiàn)LAIR圖像上呈高信號(hào) 兩個(gè)特征變量 位置：腦室旁、深部等 量（嚴(yán)重程度）：定量、半定量,腦白質(zhì)高信號(hào)的影像學(xué)診斷,分級(jí)方法 Fazekas scale Rotterdam Scan Study (RSS) scale Scheltens scale 目前尚無統(tǒng)一的標(biāo)準(zhǔn) Fazekas scale最簡單實(shí)用,腦白質(zhì)高信號(hào)的影像學(xué)診斷,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,腦白質(zhì)高信號(hào)的影像學(xué)診斷,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,腦白質(zhì)高信號(hào)的影像學(xué)診斷,Fazekas scale-DWMH Grade 1,腦白質(zhì)高信號(hào)的影

34、像學(xué)診斷,Fazekas scale-DWMH Grade 2,腦白質(zhì)高信號(hào)的影像學(xué)診斷,Fazekas scale-DWMH Grade 1,腦微出血,Cerebral microbleed 腦微出血是一種亞臨床的終末期微小血管病變導(dǎo)致的含鐵血黃素沉積。 1996年Offenbancher首次提出，GRE-T2*序列 在T2*或SWI序列上可見的圓形或卵圓形小灶信號(hào)丟失（通常直徑在2-5mm，也可大至10mm），病灶在CT、FLAIR、T1和T2序列上均不可見。,腦微出血,腦微出血的影像學(xué)診斷,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,腦微出血,腦微出血的好發(fā)部位： 皮質(zhì)及皮質(zhì)下（50.7%）、基底節(jié)及丘腦（34.1%） 腦干（9.0%）、小腦（6.2%） 高血壓與淀粉樣腦血管病微出血部位不同,腦萎縮,Brain atrophy 與肉眼可見的局灶損傷如外傷和梗死不相關(guān)的腦容量的減少。,Lancet Neurol 2013; 12: 822838

37、,不同腦小血管病的影像區(qū)別,Lancet Neurol 2013; 12: 822838,VCI的診治新進(jìn)展,VCI的定義/診斷標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),與VaD相關(guān)的腦影像學(xué)損害,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.,與VaD相關(guān)的腦影像學(xué)損害,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.,與VaD相關(guān)的腦影像學(xué)損害,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的診治新進(jìn)展,VCI的定義/診斷標(biāo)準(zhǔn) VCI的神經(jīng)心理學(xué)評(píng)估 VCI的影像學(xué)診斷 如何確定影像學(xué)與認(rèn)知損害的關(guān)系 VCI的治療進(jìn)展 小結(jié),VCI的治療,VCI治療首先應(yīng)給于病因治療。出現(xiàn)癥狀時(shí)可給于對(duì)癥治療藥物 針對(duì)血管因素以防治卒中的治療 特異針對(duì)提高認(rèn)知水平的藥物治療 加強(qiáng)康復(fù)訓(xùn)練、積極開展非藥物治療,血管危險(xiǎn)因素/腦血管病變是VCI的起始環(huán)節(jié),危險(xiǎn)因素 首要病理學(xué) 血管改變 終末期結(jié)果 中間因素 后果,認(rèn)知功能損害,高血壓,糖尿病,吸煙,高脂血癥,炎癥,動(dòng)脈粥樣硬化,動(dòng)脈僵硬度,內(nèi)皮損傷,小血管病 血管/管腔狹窄 心功能不