神经科学进展认知功能障碍课件

1、认知功能障碍诊断、治疗新观念123痴呆是一种获得性多认知障碍疾病，通常包含记忆损害以及非谵妄条件下的至少其他一种认知功能损害失语、失用、失认和执行功能受损（归纳、计划、启动、排序、跟踪、终止）。45Wimo A, et al. Alzheimers Disease International World Alzheimer Report 2010.6修改至Cummings JL. Primary Psychiatry. Vol 15, No 2. 20087阿尔茨海默病（Alzheimers disease）AD (AD-P & AD-C) 的新理念、诊断新指南NIA2011AD研究热点AD治

2、疗及预防新进展血管性认知功能障碍（Vascular Cognitive Impairment）FTDP-17病例报道8910Alois Alzheimer，1864-1915，德国神经病理学家、精神病学家。1906年11月3日，第一次定义了阿尔茨海默病。1901年，Alzheimer在Frankfurt Asylum遇见患者Mrs. Auguste Deter，一位有着短期记忆丧失在内的各种奇怪行为症状的患者。随后，Alzheimer对其进行了随访。1906年， Mrs. Deter去世，她的脑组织与病史被送往Munich的Kraepelin实验室。于是，Alzheimer与两位意大利同事通过

3、组织染色发现了淀粉样斑块和神经纤维缠结。最后于1906年11月3日，Alzheimer进行了第一次早老性痴呆临床与病理特征的报道。11A, Tau内侧颞叶萎缩、颞顶叶低代谢记忆认知行为障碍121314AD (AD-P & AD-C) 的新理念、诊断新指南NIA2011 15Lancet Neurol 2010; 9: 111827The International Working GroupHoward H FeldmanJeff rey L CummingsPhilip ScheltensNew research criteria16Diagnosis of AD: High accurac

4、y, at earliest stageRevising AD definition “dual clinicopathological entity”(1) 临床表型：a progressive dementia episodic memory impairment as a defining feature and involvement of other cognitive domains or skills,(2) 特异的神经病理改变intraneuronal (neurofibrillary tangles), extracellular parenchymal lesions (s

5、enile plaques),synaptic loss and vascular amyloid deposits.AD “双重临床生物学实体”: in-vivo biological evidence of Alzheimers pathology17病理生理升级模式P Tau分子病理变化地形学变化临床表型个体易感性Co-morbidity病理损害和生物标记物密切相关18AD的病理级联动态生物标志物模型生物标记物和临床表型密切相关Extent of biomarkers19AD两个临床阶段: AD-P and AD-CAD-P: AD-pathophysiological process

6、AD-C: Clinical phases of AD as “AD-Clinical”including not only AD dementia, but also MCI due to AD-PBetween AD-P and AD-CTime lag: 10 yrs or more (evidence: genetic at-risk and aging cohorts)Extent of biomarkers as predictor?Modulate the relationship between AD-P and AD-C“a specific threshold or reg

7、ional distribution of AD pathology, and/or a specific combination of biomarker abnormalities” remains unknownTo be clarifiedAD could one day be diagnosed preclinically by the presence of biomarker evidence of AD-P, which may eventually guide therapy before the onset of symptoms.The hypothesis that m

8、any individuals with laboratory evidence of AD-P are indeed in the preclinical stages of AD, and determine which biomarker and cognitive profiles are most predictive of subsequent clinical decline and emergence of AD-C.20New Research Criteria framework for the Diagnosis of AD新：病理生理标记物适用于各阶段的AD新：AD传统

9、的单一的临床实体转化为双重的临床和病理实体的结合新：AD的诊断是临床伴活体病理肯定的诊断，不再是可能或很可能的单一的临床诊断，尸检只用于验证诊断the International Working GroupClinically symptomatic Typical AD Atypical AD AD dementia Mixed AD Prodromal ADClinically asymptomatic Preclinical states of AD “asymptomatic at-risk state for AD” “presymptomatic AD” Mild cognitiv

10、e impairment21A new lexicon for Alzheimers diseaseAD涉及两个临床阶段: 前驱期AD and AD dementia前驱期AD = memo+, bio+，无痴呆，一定进展为ADD临床前期AD：无症状AD的危险状态:不诊断AD，(memo-, bio+)，无AD症状，条件转化为AD症状前期不诊断AD，(memo-, bio-)，无AD症状，有AD单基因突变MCI 不诊断AD，(memo-, bio-)，无AD症状，不一定转化为AD22New Research Criteria framework for the Diagnosis of ADA

11、D dementia phase:Typical ADearly & progressive episodic memory, remains dominant in later stages, followed by other CI and NPIsupported by 1 in-vivo biomarkers of Alzheimers pathologyMixed ADfully fulfil the diagnostic criteria for typical ADpresent with clinical and brain imaging/biological evidenc

12、e of other comorbid disordersAtypical ADconfirmed neuropathologically as being AD with atypical features include non-amnestic focal cortical syndromes, such as progressive non-fluent aphasia, logopenic aphasia, and posterior cortical atrophythe International Working Group23Recommendations for diagno

13、sisClinical history 应有知情者补充 (Level A).A neurological and physical examination, ADL assessed (Level A).Cognitive assessment (Level A).For questionable or very early AD (Level B)Assessment of BPSD (Level A).Assessment of co-morbidity should always be considered as a possible cause of BPSD (Level C).Bl

14、ood levels of folate, vitamin B12, thyroid stimulating hormone, calcium, glucose, complete blood cell count, renal and liver function tests should be evaluated at the time of diagnosis serological tests for syphilis, borelia and HIV might also be needed in cases with atypical presentation or clinica

15、l features suggestive of these disorders (good practice point). 2425Probable AD dementia with increased level of certaintyAll patients who met criteria for “probable AD” by the 1984 NINCDSADRDA criteriaProbable AD dementia with documented declineProgressive cognitive declineNot for increase AD patho

16、physiology.Probable AD dementia in a carrier of a causative AD genetic mutationEvidence of a causative genetic mutation (in APP, PSEN1, or PSEN2)Not for carriage of the 34 alleleIncrease AD pathophysiology 26Probable AD dementia with evidence of the AD pathophysiological processIncrease the certaint

17、y: clinical dementia syndrome is AD pathophysiological process.Biomarkers of brain amyloid-beta (Ab) protein depositionBiomarkers of downstream neuronal degeneration or injuryNot advocate: use of AD biomarker tests for routine diagnostic purposes at the present timeBiomarkers: appropriately designed

18、, standardization of biomarkers from one locale to another, varying degrees in community settingsuseful in three circumstances: investigational studies, clinical trials, and as optional clinical tools for use where available and when deemed appropriate by the clinician272829Medial temporal lobe atro

19、phy30Multidetector CT in dementia64 slices, 0.6 mm slice collimation, 5 sec acquisition timeWattjes M, et al Radiology, 200931HippocampusGyrus parahippocampalisEntorhinal cortexVolumetry of MTA32磷酸化Tau-蛋白ng/I（正常值0.149）5375972230.0413334Silverman DH, Small GW, Chang CY, et al. Positron emission tomog

20、raphy in evaluation of dementia: Regional brain metabolism and long-term outcome. Journal of the American Medical Association 2001;286:2120-2127.FDG PET -sensitivity of 93% (191/206) and specificity of 76% (59/78)-in pathologically verified cases sensitivity was 94% and specificities of 73% (AD) and

21、 78% (other dementias);-a negative PET scan indicates no progression in a 3 year follow-up3536CSF biomarkers: Over 50 studies covering more than 3000 cases Eelevation of CSF tau：a relatively accurate marker to identify AD 53. Reduced CSFAb42：indicative of AD dementia with a se of 85% and a sp of 87%

22、, but Ab42 may not be able to discriminate between AD and other forms of dementia, such as vascular dementia and frontotemporal dementia on an individual basis 52,54. Eelevation of CSF phosphorylated tau also demonstrate diagnostic potential, but some overlap between AD dementia and other dementias

23、reduces the diagnostic value. Simultaneously measure: Importantly for early diagnosisa combination of high CSF tau & low CSF Ab42 can identify about 95% of individuals with MCI who will eventually develop AD 52.37D1182王效茹 女 61岁（1949年） 初中 工人北京市脑脊液：2010-9-30序号 检验项目检验结果提示单位参考值1磷酸化Tau-蛋白 131ng/I10000ng/

24、I-淀粉体 1-42/1-400.14938Neurochemical Dementia Diagnostics in Alzheimers DiseaseWhere Are We Now and Where Are We Going?Posted: 09/30/2011; Expert Rev Proteomics.2011;8(4):447-458. Our recently published preliminary study demonstrated that NDD characterizes with higher sensitivity and shows alteration

25、s earlier than single-photon emission computed tomography neuroimaging, whereas the latter characterizes with better specificity and correlation with the disease severity.39Where are we now?The sensitivity and specificity of A142 alone to distinguish AD from elderly controls were 78 and 81%, respect

26、ively, in the study by Hulstaert et al .The meta-analysis of Sunderland et al. was based on data from 17 reports on A42 and 34 reports on CSF Tau in AD, and all of these studies reported increased CSF total Tau in AD.recently shown that the phosphorylated Tau (pTau)396/404 to total Tau ratio in CSF

27、could discriminate AD from other dementias and neurological disorders with a sensitivity of 96% and specificity of 94% .Tau protein phosphorylated at both threonine 231 and serine 235 was increased in patients with mild cognitive impairment (MCI) who developed AD during follow-up. 40Where are we now

28、?41Where are we going?Finding of novel biomarkers (characterizing with better diagnostic-related performance, such as improved sensitivity and/or specificity, better robustness or price); Searching for biomarkers in other, more easily accessible body fluids (e.g., in blood); Improving the analytical

29、 performance of the CSF biomarkers already available (better precision and correctness of measurements and improvement of inter-laboratory comparison of results); Minimizing the volume of CSF required to enable improved management of the samples (for example by the application of multiplexing techno

30、logies). 42Where are we going?43no gold standard of AD diagnosis exists 4445AD研究热点（1） TOMM40：A newly identified risk gene for AD TOMM40基因poly-T长度多态性与大脑灰质萎缩相关：研究一： 70例 APOE 3纯合子健康成年人（平均年龄57岁），其中TOMM40 poly-T 长度VL/VL型 33例，s/s型 37例 容量成分形态计量法测定脑灰质体积，发现 VL/VL TOMM40组脑灰质（腹侧扣带回后部和楔前叶）体积明显低于s/s组Sterling C.

31、Johnson, Ph.D. University of Wisconsin46AD研究热点（1） TOMM40：A newly identified risk gene for AD TOMM40基因poly-T长度多态性与记忆衰退相关：研究二： 726例有AD家族史，并已接受TOMM40 和APOE基因分型的中年人纳入研究，平均年龄54岁，其中高危版TOMM40 229例，低危版TOMM40 129例 RAVLT（Rey Auditory Verbal Learning Test)显示高危版TOMM40组学习记忆能力明显低于低危版TOMM40组，并且该结果与APOE基因型无关Mark Sa

32、ger, MD. University of Wisconsin47AD研究热点（2） LCPs，New Imaging Tool For Study Of Protein Deposites in AD Patients运用新型生物标记物 LCPs (luminescent conjugated polymers)发光共轭多聚体，研究AD患者脑内蛋白沉积的不同形态APOE 4 / 4基因型AD患者斑块核心区和脑血管壁淀粉样物质形态不同，而APOE 3 / 3 基因型无此区别APOE 4 / 4基因型AD患者脑内神经原缠结密度明显高于APOE 3 / 3 基因型Hannah Brautigam

33、, BS. Mount Sina School of Medicine48AD研究热点（3） Intranasal Insulin shows some benefits in AD and MCI经鼻腔胰岛素治疗有助于改善早期AD和MCI患者的认知和日常生活功能： 109例AD或MCI患者分别接受20/40U胰岛素或安慰剂治疗，经鼻给药4个月，于基线、治疗第2个月、第4个月、治疗接受后2个月随访 15例胰岛素治疗并接受CSF检测的患者中，记忆和功能状态的改善与CSF tau/A42比值改善相关延迟故事回忆ADAS-CogDSRSADAS-ADL20U Insulin/placeboP=0.0

34、201P=0.005440U Insulin/placeboP=0.0095Suzanne Craft, PhD. University of Washington/VA puget Sound49AD治疗及预防 Once Daily Donepezil 23 mg Extended Release Is Well Tolerated 高剂量多奈哌齐23mg缓释片在中重度AD患者的治疗中具有安全性 为期24周，全球多中心双盲对照研究，纳入病例1434,平均年龄73.8岁，女性62.8%M.Moline, Eisai Inc. Woodcliff Lake, NJ, USADonepezil 2

35、3mg/dN=963Donepezil 10mg/dN=471TEAE73.7%63.7%Serious TEAE8.3%9.6%Discontinuation rate 18.6%7.9%50AD治疗及预防 Beta Amyloid Immunotherapy with Bapineuzumab in AD May Also Reduce Tau靶向Beta amyloid 的免疫治疗可能有助于改善神经退行性改变进程 多中心、随机、双盲、安慰剂平行对照的Bapineuzumab 剂量爬坡研究Kaj Blennow, MD, PhD. University of Gothenburg, Swe

36、denDecrease in CSF P-tau ( bapineuzumab vs. placebo )USA (n=20/15)p=0.0564the United Kingdom(n=7/4)P0.05Both studiesP=0.027051AD治疗及预防 Physical activity, Tea, Vitamin D, Walnuts Possibly Maintain Cognitive Ability 3个长期、大规模临床观察显示： 体力活动结合一定的膳食成分（茶，维生素D）可能与维持老年人认知功能和降低AD风险相关转基因小鼠AD模型研究显示： 膳食补充核桃可能有利于脑功能

37、改善52BPSD的识别与干预53定义BPSD是痴呆病人中常见的知觉、思维内容、心境与行为方面紊乱的症状群它包括通过对病人的观察识别的症状；和通过精神检查与病史采取了解的症状54精神病性症状幻觉1妄想1身份识别障碍2情感症状抑郁1情感淡漠1情感高涨1焦虑1脱抑制1行为症状异常运动行为1易激惹1激越/攻击行为1睡眠紊乱1刻板行为3食欲亢进4进食紊乱1性功能亢进4AD相关的行为与精神症状（BPSD）1Cummings. Neurology. 1997;48(suppl 6):S10-S16; 2Mendez MF et al. J Nerv Ment Dis. 1992;180:94-6; 3Nya

38、tsanza S, et al. J Neurol Neurosurg Psychiatry. 2003;74:1398-402; 4Burns A et al. Br J Psychiatry. 1990;157:86-94.55国内痴呆患者BPSD症状的患病率 解恒革,王鲁宁等.北京部分城乡社区老年人和痴呆患者神经精神症状的调查.中华流行病学杂志2004,10:829-32最常见的BPSD症状为抑郁、淡漠、焦虑、睡眠障碍和易激惹56n=170n=595n=571频率 % 痴呆进展中精神行为症状越来越明显57淡漠 缺乏兴趣 3PHRC-PRE-AL 245 MCI 个体的发展平均年龄 = 7

39、2 5.5MMSE = 27.5 1.33年后MCI-AD转变情况n = 59 (27.2%)MCI 精神行为症状1010名MCI被试中 59% 存在精神行为症状最常见的行为症状: 淡漠 抑郁焦虑 易激惹 夜间行为Feldman et al, Neurology 2004; Robert et al, Clin Neurol & Neurosurg, 2006; Robert et al, Am JGP, 200858观察交谈询问观察交谈询问测查596061BPSD评定SCAG(老年临床评定量表)Behave-AD(阿尔茨海默病行为异常量表)DBD(痴呆行为障碍量表)CMAI(CM激越问卷)N

40、PI(神经精神科问卷)62与抑郁的鉴别抑郁AD情绪忧伤，低落淡漠认知过程缓慢错误悲观厌世有无人格变化不显著显著日常生活能力懒动差自知力有，求治无，不求医起病形式一定生活事件后数周至2月内起病潜隐、缓慢，以年计按照抑郁治疗疗效不佳的老年人，应考虑存在AD的可能63与谵妄的鉴别发病急性缓慢病程波动性，白天有时清醒，夜间则加重一天之内无变化病期几小时到数周几个月或数年觉醒度降低清楚机警度异常降低或增高一般正常注意力缺乏选择性，注意分散相对地不受影响定向力一般时间定向受损，对熟悉的地方和人物呈生疏倾向常有障碍记忆力即刻记忆力受损 远近记忆受损思维零乱贫乏知觉错觉和幻觉常见（视觉）较少见言语不连贯使用词

41、句困难睡眠清醒周期常被打乱时睡时醒躯体疾病或药物中毒可单独或同时存在常少见64BPSD相关的神经递质改变65干预策略66痴呆的诊断 告知诊断（采取恰当的方式） 用朴实的语言解释诊断或病理学特点积极乐观地探讨照料与保健方案 保健方案 痴呆的治疗与照料药物治疗心理社会干预为照料者提供支持定期访视，修改保健方案晚期关怀照料及为照料者提供居丧咨询(QoLDEM, 2006)67BPSD的治疗目标延缓症状的出现 缓解症状的强度和频率减少抗精神病药物的使用68非药物干预一线选择中重度症状是药物治疗的指征，但也应与非药物处理相结合对非药物处理反应良好的症状：轻度抑郁和淡漠；漫游与踏步；重复提问与作态69非药

42、物干预1Cohen-Mansfield J. Am J Geriatr Psychiatry. 2001;9:361-81; 2Caltagirone et al. Drugs Aging 2005;22(Suppl 1):1-26.人员培训特设的活动社会接触: 宠物、一对一、家庭录像照料者支持过渡性医疗/护理干预 (助听器, 行为治疗, 疼痛处理)感官改善: 音乐, 按摩, 光照治疗70会导致BPSD恶化的照护者行为 突然且非预期性地改变患者的生活习惯与环境挑动与患者进行“权利之争”给患者提出超过他或她能力的要求过分地苛求患者忽视患者的要求过分刻板或循规蹈矩反复提问或询问以“使”患者记住什么

43、事情在患者面前表现愤怒与攻击恶感与愤怒加重71BPSD 药物治疗抗痴呆药物胆碱酯酶抑制剂 (多奈哌齐, 卡巴拉汀, 加兰他敏)NMDA受体拮抗剂 (美金刚)其它精神药物抗精神病药 (SDA)心境稳定剂抗抑郁剂72Holmes C et al. Neurology. 2004;63:214-9; Cummings et al. Am J Psychiatry. 2004;161:532-8; Finkel et al. Int J Geriatr Psychiatr. 2004;19:9-18; Feldman H et al. Neurology. 2001;57:613-21; Gauthi

44、er S et al. Int J Psychogeriatr. 2002;14:389-404; Lee et al. BMJ. 2004;329:75; Pratt et al. Int J Clin Prac. 2002;56:710-7.Rockwood K, et al. Inter J Geria Psy 2004;19:954-960. 胆碱酯酶抑制剂已有研究报道, 胆碱酯酶抑制剂(ChEIs)对AD患者的行为问题具有改善作用。与大多数精神药物不同,胆碱酯酶抑制剂似乎能治疗多种行为症状 (如, 情感的和精神病性的)。胆碱酯酶抑制剂通常耐受性好。临床医生调查显示，多奈哌齐改善痴呆患

45、者精神行为症状最主要是淡漠、情感症状和激越。73Romn et al Neurology 1993血管性痴呆: VaDVaD 是指由各种脑血管病（ cerebrovasculardisease, CVD），包括梗死、出血和缺血相关性改变所导致的痴呆综合征VaD诊断标准均强调必须有痴呆和CVD的证据（病史、临床表现和神经影像学证据）以及两者之间存在相关性（即卒中后一定时间内发生痴呆）VaD 的诊断分为2 步：首先要确定为痴呆，然后再与AD相区别（根据血管危险因素、缺血评分和影像学变化等）。74SUBTYPES OF VCI/VaD : VASCULAR MECHANISMS AND CHANGE

46、S IN THE BRAIN WML = white matter lesionCorticalStrategic Subcortical VaD infarct ischemicVaDVascular mechanisms VaD SIVDLarge-vessel disease Cardiac embolic events Hypoperfusion Small-vessel disease Changes in the brainArterial territorial infarct Distal field (watershed) infarct Lacunar infarct Fo

47、cal, diffuse WMLs Incomplete ischaemic injury Heterogeneity+ +75大血管疾病关 键 部 位 的 皮 层 梗 塞额叶 海马, 前脑底部角回顶叶 失语、失用、 脱抑制、淡漠记忆减退结构能力减退失读、失写皮层型痴呆大面积皮层灶性病变76小血管疾病关键部位的皮层下梗塞破坏特异性的额叶皮层下通路或者丘脑与皮层间的非特异性联系 丘脑, 尾状核, 内囊人格改变注意力减退淡漠执行功能障碍皮层下痴呆小血管疾病皮层-皮层下回路VaD77并不是有卒中病史，就能诊断血管性痴呆NINDS-AIREN很可能VaD的诊断很可能VaD的临床诊断标准包括痴呆定义为认

48、知功能从以前的高功能水平的下降，表现为记忆力的受损和两个或两个以上领域的认知缺陷（定向力，注意力，语言，视觉空间能力，执行能力，运动控制或实践），最好经过明确的临床检查和有神经精神学检查的记录；这种缺陷已经严重到影响日常生活能力，并且除外日常生活能力的下降是因为脑血管疾病本身的身体障碍引起；排除标准：有意识障碍，谵妄状态，精神病，严重的失语症或显著的感觉缺陷无法进行神经精神学检查。同时需除外：其他系统疾病或脑部疾病（如AD）引起的认知和记忆力受损；脑血管疾病的定义为在进行神经学检查时有与脑卒中（有或无脑卒中病史）相一致的局灶性体征，如偏瘫，面部无力，Baninski征阳性，感觉障碍，偏盲，构音

49、障碍等，并且有与脑血管疾病相关的脑部影像学证据（CT或MRI），包括：多枝大血管卒中或单枝的有重要意义的血管的梗塞（角回枝，丘脑枝，前脑基底枝，PCA或ACA区域）轻度的皮质受累及多个基底神经节和白质的腔隙灶（1）或广泛的脑室周围的白质病变或是上述的组合美国国立神经疾病卒中研究所和瑞士神经科学研究国际协会 78并不是有卒中病史，就能诊断血管性痴呆NINDS-AIREN很可能VaD的诊断痴呆与脑血管疾病间有相关性，表现为下述一项或一个以上：在确定的脑卒中发生后的3个月内开始出现痴呆认知功能的突然恶化；或波动，认知功能的逐步进行性减退。与可能VaD相一致的临床表现，包括：早期出现的步态障碍（小步步

50、态，运动失用或帕金森步态）。既往有不稳定或经常出现无原因的摔到病史。不能用泌尿系疾病解释的早期尿频、尿急和泌尿系症状。性格和情绪的改变，意志力丧失，抑郁，情感不能控制，其他皮层下的功能障碍，包括精神运动延迟和执行功能的异常。一些不符合Vad的临床特征：早期出现的记忆力受损和进行性恶化的记忆力和其他认知功能障碍，如语言（经皮质的感觉性失语症），运动技巧（运动性失用）和感觉（失认），但在脑部影像学上无相应的局限性病灶；除了认知功能障碍，缺乏局灶性的神经学体征；CT或MRI上缺乏脑血管疾病的表现；用于研究目的时可将血管性痴呆按临床，影像学和神经精神学特点进行分类，分为下述亚类或情况：皮质血管性痴呆；

51、皮层下血管性痴呆；宾斯万格痴呆（Binswangers）；丘脑性痴呆；79VaD的影像学检查结果不同于ADAD血管性痴呆80AD & VD 鉴别诊断临床特征认知, 精神行为伴随神经症状发病及进展方式, 首发症状预后生物学标记: CSF MRI流行病家族史, 基因多态性发病机理81首发症状（面谈：患者及知情者）首发症状记忆（视觉空间损伤）：AD行为：FTD，DLB (行为早于认知损害数年)语言（独立出现2年）：FTLD，DLB (罕见AD)实践能力：CBD，AD执行能力：AD，VaD，FTD，DLB初发症状谵妄： VaD早期症状早期出现幻觉： VaD，DLB外貌个人和家族疾病史（ AD，FTD

52、）病程（治疗史）82认知功能表现皮质下表现（血管性痴呆）与额叶损伤类似智能反应迟缓执行功能不良注意力障碍记忆：自由回忆差、提示有效、延迟回忆保留全面认知障碍83行为表现评估: NPI (Cumming 1994), FBS (Lebert 1998), FBI (Kertesz 1997) 额叶行为： FTD幻觉: DLB，VaD易激惹，情感过度，抑郁, 冷漠：VaD妄想： FTD，DLB84AD的病理学表现VaD的病理学表现记忆力受损行为症状注意力受损执行功能障碍结构运用问题意识波动视觉-结构的障碍语言问题与临床相关的痴呆症状85AD & VaD 鉴别诊断ADVaD患病率（65岁以上老人）4

53、.8%1.1%年龄较晚较早病史少有高血压、卒中、动脉粥样硬化病史常有高血压、卒中、动脉粥样硬化病史发病及进展方式慢性起病，缓慢进展急性起病，起伏性进展认知症状全面性，早期以情景记忆障碍为主；自知力差；斑片状，早期以执行功能减退为主；自知力保持良好精神症状少有强笑强哭，人格保留较差情感症状不稳定常有强笑强哭，人格保留较好局灶性神经系统体征无有CT/MRI脑萎缩明显，存在内颞叶萎缩：海马结构、内嗅皮层、杏仁核体积缩小卒中病灶Hachinski 评分=7分PET双侧颞叶糖代谢减低局灶性糖代谢减低脑脊液A1-42 降低、总tau或磷酸化tau增高，或三者同时存在正常AD 最早期损害位于颞叶内侧海马，因此记忆和学习能力损害最早，也最突出VaD：额叶和基底节是小血管病变的好发部位，执行功能损害和情感行为异常出现最早且最为突出，其特征是智能过程慢、决策困难、组织能力差、难以调节、注意力不集中和表情淡漠86FTDP-17病例报道87临床表现患者，女，44岁40岁时逐渐出现右上肢震颤，静止性，运动时消失，1年左右渐累及右下肢；渐感肢体僵硬感，运动迟缓，面部表情减少；便秘；偶有流涎；记忆力下降不明显2007年5月门诊诊