神经科学进展认知功能障碍.ppt

1、认知功能障碍诊断、治疗新观念认知功能障碍诊断、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）。45WimoA,etal.AlzheimersDiseaseInternationalWorldAlzheimerReport2010.6修改至CummingsJL.PrimaryPsychiatry.Vol15,No2.20087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治疗及预防新进展血

2、管性认知功能障碍（VascularCognitiveImpairment）FTDP-17病例报道8910AloisAlzheimer，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FrankfurtAsylum遇见患者Mrs.AugusteDeter，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组织染色发现了淀粉样斑块和神经纤

3、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内内侧颞叶萎叶萎缩、颞顶叶低代叶低代谢记忆认知行知行为障碍障碍121314AD(AD-P&AD-C)的新理念、的新理念、诊断新指南诊断新指南NIA2011 15Lancet Neurol 2010;9:111827The International Working GroupHoward H FeldmanJeff rey L CummingsPhilip ScheltensNew research criteria16Diagnosis of AD:High accuracy,at

4、 earliest stageRevising AD definition“dual clinicopathological entity”(1)临床表型：aprogressivedementiaepisodicmemoryimpairmentasadefiningfeatureandinvolvementofothercognitivedomainsorskills,(2)特异的神经病理改变intraneuronal(neurofibrillarytangles),extracellularparenchymallesions(senileplaques),synapticlossandva

5、scularamyloiddeposits.AD“双重临床生物学实体实体”:in-vivobiologicalevidenceofAlzheimerspathology17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病理损害和生物标记物密切相关病理损害和生物标记物密切相关病理损害和生物标记物密切相关18AD的病理级联动态的病理级联动态生物标志物生物标志物模型模型生物标记物和临床表型密切相关生物标记物和临床表型密切相关Extentofbiomarkers19AD两个临床阶段两个临床阶段:AD-P and AD-CAD-P:

6、AD-pathophysiologicalprocess AD-C:ClinicalphasesofADas“AD-Clinical”includingnotonlyADdementia,butalsoMCIduetoAD-PBetween AD-P and AD-CTimelag:10yrsormore(evidence:geneticat-riskandagingcohorts)Extentofbiomarkersaspredictor?ModulatetherelationshipbetweenAD-PandAD-C“aspecificthresholdorregionaldistrib

7、utionofADpathology,and/oraspecificcombinationofbiomarkerabnormalities”remainsunknownTo be clarifiedADcouldonedaybediagnosedpreclinicallybythepresenceofbiomarkerevidenceofAD-P,whichmayeventuallyguidetherapybeforetheonsetofsymptoms.ThehypothesisthatmanyindividualswithlaboratoryevidenceofAD-Pareindeedi

8、nthepreclinicalstagesofAD,anddeterminewhichbiomarkerandcognitiveprofilesaremostpredictiveofsubsequentclinicaldeclineandemergenceofAD-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theInternati

9、onalWorkingGroupClinicallyClinicallysymptomaticsymptomaticTypicalADAtypicalADADdementiaMixedADProdromalADClinicallyClinicallyasymptomaticasymptomaticPreclinicalstatesofADPreclinicalstatesofAD“asymptomaticat-riskstateforAD”“presymptomaticAD”MildcognitiveimpairmentMildcognitiveimpairment21A new lexico

10、n for Alzheimers diseaseAD涉及两个临床阶段涉及两个临床阶段:前驱期ADandADdementia前驱期AD=memo+,bio+，无痴呆，一定进展为ADD临床临床前期AD：无症状AD的危险状态:不诊断AD，(memo-,bio+)，无AD症状，条件转化为条件转化为AD症状前期不诊断AD，(memo-,bio-)，无AD症状，有有AD单基因突变单基因突变MCI不诊断AD，(memo-,bio-)，无AD症状，不一定转化为不一定转化为AD22New Research Criteria framework for the Diagnosis of ADAD dementia

11、 phase:TypicalADearly&progressiveepisodicmemory,remainsdominantinlaterstages,followedbyotherCIandNPIsupportedby1in-vivobiomarkersofAlzheimerspathologyMixedADfullyfulfilthediagnosticcriteriafortypicalADpresentwithclinicalandbrainimaging/biologicalevidenceofothercomorbiddisordersAtypicalADconfirmedneu

12、ropathologicallyasbeingADwithatypicalfeaturesincludenon-amnesticfocalcorticalsyndromes,suchasprogressivenon-fluentaphasia,logopenicaphasia,andposteriorcorticalatrophytheInternationalWorkingGroup23Recommendations for diagnosisClinicalhistory应有知情者补充(LevelA).Aneurologicalandphysicalexamination,ADLasses

13、sed(LevelA).Cognitiveassessment(LevelA).ForquestionableorveryearlyAD(LevelB)AssessmentofBPSD(LevelA).Assessmentofco-morbidityshouldalwaysbeconsideredasapossiblecauseofBPSD(LevelC).Bloodlevelsoffolate,vitaminB12,thyroidstimulatinghormone,calcium,glucose,completebloodcellcount,renalandliverfunctiontes

14、tsshouldbeevaluatedatthetimeofdiagnosisserologicaltestsforsyphilis,boreliaandHIVmightalsobeneededincaseswithatypicalpresentationorclinicalfeaturessuggestiveofthesedisorders(goodpracticepoint).2425Probable AD dementia with increased level of certaintyAllpatientswhometcriteriafor“probableAD”bythe1984N

15、INCDSADRDAcriteriaProbableADdementiawithdocumenteddeclineProgressivecognitivedeclineNotforincreaseADpathophysiology.ProbableADdementiainacarrierofacausativeADgeneticmutationEvidenceofacausativegeneticmutation(inAPP,PSEN1,orPSEN2)Notforcarriageofthe34alleleIncreaseADpathophysiology26Probable AD demen

16、tia with evidence of the AD pathophysiological processIncrease the certainty:clinicaldementiasyndromeisADpathophysiologicalprocess.Biomarkersofbrainamyloid-beta(Ab)proteindepositionBiomarkersofdownstreamneuronaldegenerationorinjuryNot advocate:useofADbiomarkertestsforroutinediagnosticpurposesatthepr

17、esenttimeBiomarkers:appropriatelydesigned,standardizationofbiomarkersfromonelocaletoanother,varyingdegreesincommunitysettingsuseful in three circumstances:investigationalstudies,clinicaltrials,andasoptionalclinicaltoolsforusewhereavailableandwhendeemedappropriatebytheclinician272829Medial temporal l

18、obe atrophy30Multidetector CT in dementia64slices,0.6mmslicecollimation,5secacquisitiontimeWattjesM,etalRadiology,200931HippocampusGyrus parahippocampalisEntorhinal cortexVolumetry of MTA32磷酸化Tau-蛋白ng/I（正常值0.149）5375972230.0413334SilvermanDH,SmallGW,ChangCY,etal.Positronemissiontomographyinevaluatio

19、nofdementia:Regionalbrainmetabolismandlong-termoutcome.JournaloftheAmericanMedicalAssociation2001;286:2120-2127.FDG PET-sensitivityof93%(191/206)andspecificityof76%(59/78)-inpathologicallyverifiedcasessensitivitywas94%andspecificitiesof73%(AD)and78%(otherdementias);-anegativePETscanindicatesnoprogre

20、ssionina3yearfollow-up3536CSF biomarkers:Over50studiescoveringmorethan3000casesOver50studiescoveringmorethan3000casesEelevationofCSFtau：arelativelyaccuratemarkertoidentifyAD53.ReducedCSFAb42：indicativeofADdementiawithaseof85%andaspof87%,butAb42maynotbeabletodiscriminatebetweenADandotherformsofdement

21、ia,suchasvasculardementiaandfrontotemporaldementiaonanindividualbasis52,54.EelevationofCSFphosphorylatedtaualsodemonstratediagnosticpotential,butsomeoverlapbetweenADdementiaandotherdementiasreducesthediagnosticvalue.Simultaneouslymeasure:ImportantlyforearlydiagnosisacombinationofhighCSFtau&lowCSFAb4

22、2canidentifyabout95%ofindividualswithMCIwhowilleventuallydevelopAD52.37D1182D1182王效茹王效茹 女女 6161岁（岁（19491949年）年）初中初中 工人工人北京市北京市脑脊液：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/I-淀粉体 1-42/1-400.14938Neurochemical Dementia Diagnostics Neurochemical Dementia Diagnostics in Alzheimers Diseasein A

23、lzheimers DiseaseWhere Are We Now and Where Are We Going?Posted:09/30/2011;ExpertRevProteomics.2011;8(4):447-458.OurrecentlypublishedpreliminarystudydemonstratedthatNDDcharacterizeswithhighersensitivityandshowsalterationsearlierthansingle-photonemissioncomputedtomographyneuroimaging,whereasthelatter

24、characterizeswithbetterspecificityandcorrelationwiththediseaseseverity.39Where are we now?Where are we now?ThesensitivityandspecificityofA142alonetodistinguishADfromelderlycontrolswere78and81%,respectively,inthestudybyHulstaertet al.Themeta-analysisofSunderlandet al.wasbasedondatafrom17reportsonA42a

25、nd34reportsonCSFTauinAD,andallofthesestudiesreportedincreasedCSFtotalTauinAD.recentlyshownthatthephosphorylatedTau(pTau)396/404tototalTauratioinCSFcoulddiscriminateADfromotherdementiasandneurologicaldisorderswithasensitivityof96%andspecificityof94%.Tauproteinphosphorylatedatboththreonine231andserine

26、235wasincreasedinpatientswithmildcognitiveimpairment(MCI)whodevelopedADduringfollow-up.40Where are we now?Where are we now?41Where are we going?Where are we going?Finding of novel biomarkers(characterizing with better diagnostic-related performance,such as improved sensitivity and/or specificity,bet

27、ter robustness or price);Searching for biomarkers in other,more easily accessible body fluids(e.g.,in blood);Improving the analytical performance of the CSF biomarkers already available(better precision and correctness of measurements and improvement of inter-laboratory comparison of results);Minimi

28、zing the volume of CSF required to enable improved management of the samples(for example by the application of multiplexing technologies).42Where are we going?Where are we going?43no gold standard of AD diagnosis existsno gold standard of AD diagnosis exists 4445ADAD研究热点（研究热点（1 1）TOMM40TOMM40：A newl

29、y identified A newly identified risk gene for AD 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.Johnson,Ph.D.University of Wisconsin46ADAD研究热点（研究热点（1 1）TOMM40TOM

30、M40：A newly identified A newly identified risk gene for AD 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 Sager,MD.University

31、of Wisconsin47ADAD研究热点（研究热点（2 2）LCPsLCPs，New Imaging Tool For New Imaging Tool For Study Of Protein Deposites in AD PatientsStudy Of Protein Deposites in AD Patients运用新型生物标记物LCPs(luminescentconjugatedpolymers)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

32、脑内神经原缠结密度明显高于APOE 3/3基因型Hannah Brautigam,BS.Mount Sina School of Medicine48ADAD研究热点（研究热点（3 3）Intranasal Insulin shows Intranasal Insulin shows some benefits in AD and MCIsome 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

33、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延迟故事回忆ADAS-CogDSRSADAS-ADL20U Insulin/placeboP=0.0201P=0.005440U Insulin/placeboP=0.0095Suzanne Craft,PhD.University of Washington/VA puget Sound49ADAD治疗及预防治疗及预防 Once Daily Donepezil 23 mg Once Daily Donepezil 23 mg Extended Release Is Well Tolera

34、ted 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 23mg/dN=963Donepezil 10mg/dN=471TEAE73.7%63.7%SeriousTEAE8.3%9.6%Discontinuationrate18.6%7.9%50ADAD治疗及预防治疗及预防 Beta Amyloid Immunotherap

35、y Beta Amyloid Immunotherapy with Bapineuzumab in AD May Also Reduce Tauwith Bapineuzumab in AD May Also Reduce Tau靶向Betaamyloid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,SwedenDecrease in CSF P-tau(bapineuzumab vs.placebo)USA(n=20/15)p=0.05

36、64theUnitedKingdom(n=7/4)P0.05BothstudiesP=0.027051ADAD治疗及预防治疗及预防 Physical activity,Tea,Vitamin Physical activity,Tea,Vitamin D,WalnutsD,Walnuts Possibly Maintain Cognitive Ability 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

37、功能改善52BPSD的识别与干预53定义定义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精神病精神病性症状性症状幻觉1妄想1身份识别障碍2情感情感症状症状抑郁1情感淡漠1情感高涨1焦虑1脱抑制1行为行为症状症状异常运动行为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(suppl6):S10-S16;2MendezMFetal.J Nerv Ment Dis.1992;180:9

38、4-6;3NyatsanzaS,etal.J Neurol Neurosurg Psychiatry.2003;74:1398-402;4BurnsAetal.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最常见的最常见的BPSDBPSD症状为抑郁、淡漠、焦虑、睡眠障碍和易激惹症状为抑郁、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淡漠淡漠 缺乏兴趣缺乏兴趣 3PHRC

39、PRE-AL245MCI个体的发展平均年龄=725.5MMSE=27.51.33年后年后MCI-AD转变情况转变情况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Feldmanetal,Neurology2004;Robertetal,ClinNeurol&Neurosurg,2006;Robertetal,AmJGP,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)NP

40、I(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句

41、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干预策略干预策略66痴呆的诊断痴呆的诊断 告知诊断（采取恰当的方式）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积极乐观地探讨照料与保健方案 保健方案保健方案 痴呆的治疗与照料痴呆的治疗与照料药物治疗药物治疗心理社会干预心理社会干预为照料者提供支持为照料者提供支持定期访视，修改保健方案定期访视，修改保健方案晚期关怀照料及为照料者提供居丧咨询晚期关怀照料及为照料者提供居丧咨询(QoLDEM,2006)67BPSD的治疗

42、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非药物干预1 1Cohen-MansfieldJ.Am J Geriatr Psychiatry.2001;9:361-81;2 2Caltagironeetal.Drugs Aging2005;22(Suppl1):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

43、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72HolmesCetal.Neurology.2004;63:214-9;Cummingsetal.Am J Psychiatry.2004;161:532-8;Finkeletal.Int J Geriatr

44、 Psychiatr.2004;19:9-18;FeldmanHetal.Neurology.2001;57:613-21;GauthierSetal.Int J Psychogeriatr.2002;14:389-404;Leeetal.BMJ.2004;329:75;Prattetal.Int J Clin Prac.2002;56:710-7.RockwoodK,etal.Inter J Geria Psy2004;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

45、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即卒中后一定时间内发生痴呆痴呆）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）。74S

46、UBTYPES OF VCI/VaD:VASCULAR MECHANISMS AND CHANGES IN THE BRAIN WML=whitematterlesionCorticalStrategicSubcorticalVaDinfarct ischemicVaDVascularmechanismsVaDSIVDLarge-vesseldiseaseCardiacemboliceventsHypoperfusionSmall-vesseldiseaseChangesinthebrainArterialterritorialinfarctDistalfield(watershed)infa

47、rctLacunarinfarctFocal,diffuseWMLsIncompleteischaemicinjuryHeterogeneity+75大血管疾病大血管疾病关关 键键 部部 位位 的的 皮皮 层层 梗梗 塞塞额叶额叶 海马海马,前脑前脑底部底部角回角回顶叶顶叶 失语、失用、失语、失用、脱抑制、淡漠脱抑制、淡漠记忆减退记忆减退结构能力减退结构能力减退失读、失写失读、失写皮层型痴呆皮层型痴呆大面积皮层大面积皮层灶性灶性病变病变76小血管疾病小血管疾病关键部位的皮层下梗塞关键部位的皮层下梗塞破坏破坏特异性的额叶皮层下通路或者丘脑与皮层间的非特特异性的额叶皮层下通路或者丘脑与皮层间的非特

48、异性联系异性联系 丘脑丘脑,尾状核尾状核,内囊内囊人格改变人格改变注意力减退注意力减退淡漠淡漠执行功能障碍执行功能障碍皮层下痴呆皮层下痴呆小血管疾病小血管疾病皮层皮层-皮层下回路皮层下回路VaD77VaDVaD的影像学检查结果不同于的影像学检查结果不同于ADADAD血管性痴呆血管性痴呆80AD&VD 鉴别诊断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:CSFMRI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行为早于认知损害数年)语言（独立出现2年）：FTLD，

49、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）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的病理学表现的病理学表现VaD的病理学表现的病理学表现

50、记忆力受损记忆力受损行为症状行为症状注意力受损注意力受损执行功能障碍执行功能障碍结构运用问题结构运用问题意识波动意识波动视觉视觉-结构的障碍结构的障碍语言问题语言问题与临床相关的痴呆症状85AD&VaD 鉴别诊断鉴别诊断ADVaD患病率（65岁以上老人）4.8%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C