癡呆診斷標準update福州

1、會計學1癡呆診斷標準癡呆診斷標準update福州福州Probable AD : A+B、C、D或E中至少一（1+1標準）核心癥狀核心癥狀A. 早期、顯著的情景記憶障礙，包括以下特點 逐漸出現(xiàn)的進行性的逐漸出現(xiàn)的進行性的記憶記憶功能下降，超過功能下降，超過6個月個月（時間標準時間標準） 客觀檢查發(fā)現(xiàn)顯著的客觀檢查發(fā)現(xiàn)顯著的情景記憶情景記憶損害，主要為損害，主要為回憶回憶障礙，在提示或再認試驗中障礙，在提示或再認試驗中不能顯著改善或恢復正常不能顯著改善或恢復正常（表明記憶的性質及損害的模式表明記憶的性質及損害的模式） 情景記憶障礙可在起病或病程中單獨出現(xiàn)，或與其它認知改變一起出現(xiàn)情景記憶障礙可在起

2、病或病程中單獨出現(xiàn)，或與其它認知改變一起出現(xiàn) （表明記憶損害可以有規(guī)律，也有一定的變異表明記憶損害可以有規(guī)律，也有一定的變異）Lancet Neurol. 2007, 8: 734-746Probable AD : A+B、C、D或E中至少一支持特征支持特征B. 存在內顳葉萎縮 MRI定性或定量測量發(fā)現(xiàn)海馬結構、內嗅皮層、杏仁核體積縮?。▍⒖纪甓ㄐ曰蚨繙y量發(fā)現(xiàn)海馬結構、內嗅皮層、杏仁核體積縮?。▍⒖纪挲g人群的常模）齡人群的常模）C. 腦脊液生物標記異常 A1-42 降低、總降低、總tau(t-tau)或磷酸化或磷酸化tau(p-tau)增高，或三者同時存在增高，或三者同時存在D. PET

3、的特殊表現(xiàn) 雙側顳葉糖代謝減低雙側顳葉糖代謝減低 其它有效的配體，如其它有效的配體，如FDDNP預見預見AD病理的改變病理的改變E. 直系親屬中有已證實的常染色體顯性遺傳突變導致的ADLancet Neurol. 2007, 8: 734-746這些支持特征大家做過嗎？國內有幾家醫(yī)院做了？Lancet Neurol. 2007, 8: 734-746 排除標準病史 突然起病突然起病 早期出現(xiàn)下列癥狀：步態(tài)不穩(wěn)、癲癇、行為異常早期出現(xiàn)下列癥狀：步態(tài)不穩(wěn)、癲癇、行為異常臨床特點 局灶性神經(jīng)系統(tǒng)癥狀體征：偏癱、感覺缺失、視野損害局灶性神經(jīng)系統(tǒng)癥狀體征：偏癱、感覺缺失、視野損害 早期的錐體外系體征早期

4、的錐體外系體征其它疾病狀態(tài)嚴重到足以解釋記憶和相關癥狀 非非AD癡呆癡呆 嚴重的抑郁嚴重的抑郁 腦血管病腦血管病 中毒或代謝異常（要求特殊檢查證實）中毒或代謝異常（要求特殊檢查證實） MRI的的FLAIR或或T2加權相內顳葉信號異常與感染或血管損害一致加權相內顳葉信號異常與感染或血管損害一致Lancet Neurol. 2007, 8: 734-746 確確診診標準標準 臨床和組織病理（腦活檢或尸檢）證實為臨床和組織病理（腦活檢或尸檢）證實為AD，病理須滿足，病理須滿足NIA-Reagan標準標準 臨床和遺傳學（染色體臨床和遺傳學（染色體, 14, 21突變）證實為突變）證實為AD“輕度認知損

5、害”在標準中提出了臨床中的認知不僅僅是認知檢查遺忘性質非遺忘性質(1) NormalEarly AlzheimersLate AlzheimersChildNo APOE-4PET Imaging Lower inferior parietal metabolism in non-demented persons with a single copy of APOE-4Genetic Risk:APOE-4Small et al, PNAS 2000; 97:6037-6042-20%-22%-12%-18%NORMAL MEMORYDEMENTIAFrom Klunk et al 2004

6、Annals of NeurologyAlzheimer disease (AD), healthy control subjects (HCS), subjects with non-AD dementias (DEM), and subjects with other neurological disorders without dementia (OTH)Alzheimer disease (AD), healthy control subjects (HCS), subjects with non-AD dementias (DEM), and subjects with other

7、neurological disorders without dementia (OTH)Alzheimer disease (AD), healthy control subjects (HCS), subjects with non-AD dementias (DEM), and subjects with other neurological disorders without dementia (OTH)APOE-4又如何？又如何？Lancet Neurol 2007, 6: 734 .Stroke,Transient Ischemic Attack, DEMENTIACardiova

8、scular diseaseAtherosclerosisModifiable risk factorsDiabetesSmokingObesityHypertensionHypercholesterolemiaCAD,Heart attack,Heart failureAdapted from Nyenhuis DL et al. J Am Geriatr Soc, 1998.Pratt RD. J Neurol Sci, 2002.Skoog I. Neuroepidemiology, 1998.Vascular risk factors Hypertension Cigarette sm

9、oking Atherosclerosis Hypercholesterolemia Diabetes mellitus Ischemic heart disease Low blood pressure Atrial fibrillation Coagulopathies Elevated homocysteine Peripheral vascular disease Myocardial infarction (MI)/angina CHF CABG. . Canadian Study of Health and Aging. CMAJ, 1994.Alzheimers disease

10、(AD)64%VaDOtherdementias 17%19% VaD is the second most common cause of dementia in western countries, and may be the most common elsewhere (e.g., Asia) Final Common PathwayCardiovascular Risk FactorsMultiple Distinct PathologiesStrategic Single InfarctsMulti-infarct Dementia Chronic SDH SAH ICH Glob

11、al (e.g., cardiac arrest) HypotensionDamage to critical cortical and subcortical structuresDamage/interruption of subcortical circuits and projectionsIschemic Damage to Cerebral Vasculature Cholinergic transmissionErkinjuntti T. CNS Drugs, 1999.Sachdev PS, et al. Med J Aust, 1999. Hnon H, et al. Neu

12、rology, 2001. Kurz AF. Int J Clin Pract, 2001.Sachdev PS, et al. Med J Aust, 1999. Hnon H, et al. Neurology, 2001. Kurz AF. Int J Clin Pract, 2001.Multiple large vessel infarctsBilateral strategic thalamic infarctsBinswangers disease3 Types of VaDSource: Stephen Salloway, MDVaDADMixedAD/VaDAmyloid p

13、laquesGenetic factorsNeurofibrillary tanglesStroke/TIAHypertensionDiabetesHypercholesterolemiaHeart diseaseKalaria RN, Ballard C. Alzheimer Dis Assoc Disord, 1999. Cholinergic deficitAmyloid plaquesGenetic factorsNeurofibrillary tanglesStroke/TIAHypertensionDiabetesHypercholesterolemiaHeart diseaseV

14、aDADAD + CVD ADVaDAD w/CVDVaD存在膽堿能功能缺陷的可能原因:尸體解剖發(fā)現(xiàn)尸體解剖發(fā)現(xiàn)VaD 可以存在基底節(jié)區(qū)的膽堿能神經(jīng)元改變可以存在基底節(jié)區(qū)的膽堿能神經(jīng)元改變 血管損害可以累積膽堿能通路血管損害可以累積膽堿能通路lNot present in controlslModerate to severe in 66% of VaD patientsVaD 患者有其他膽堿能標志的減少患者有其他膽堿能標志的減少 Binswangers 型與小血管型癡呆型與小血管型癡呆CSF中乙酰膽堿減少中乙酰膽堿減少Amenta F et al. Clin Exp Hypertens, 2

15、002.Swartz RH et al. J Stroke Cerebrovasc Dis, 2003.Selden NR, et al. Brain, 1998. Swartz RH, Black SE. J Neurol Sci, 2002. With permission from Oxford University Press.Cholinergic pathways in healthy brainWhite matter hyperintensities in VaD“輕度認知損害”No APOE-4PET Imaging Lower inferior parietal metabolism in non-demented persons with a single copy of APOE-4Genetic Risk:APOE-4Small et al, PNAS 2000; 97:6037-6042-20%-22%-12%-18%NORMAL MEMORYDEMENTIACanadian Study of Health and Aging. CMAJ, 1994.Alzheimers disease (AD)64%VaDOtherdementias 17%19%