Contents 치매의종류 신경퇴행성질환 알츠하이머병에의한치매 전두측두치매 루이체치매 혈관성치매 MID (Multi-infarct dementia: 다발성경색성치매 ) SVD (Subcortical vascular dementia: 피질하혈관성치매 ) SID (Stra

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1 치매의종류와병태생리 - 간호협회치매인력양성교육 울산의대, 서울아산병원 정신과김성윤 1

2 Contents 치매의종류 신경퇴행성질환 알츠하이머병에의한치매 전두측두치매 루이체치매 혈관성치매 MID (Multi-infarct dementia: 다발성경색성치매 ) SVD (Subcortical vascular dementia: 피질하혈관성치매 ) SID (Strategic infarct dementia: 전략적경색치매 ) 기타치매 두부외상, 중독성, 알코올, 대사성등. 조기진단및예방의중요성 : MCI, VCI 병태생리 뇌의각부위의기능과그에따른임상양상 2

3 치매의종류 알쯔하이머치매 혈관성치매 루이체치매 파킨슨병치매 전두측두엽치매 외상성치매 알코올성치매...

4 치매의종류 전체치매 알츠하이머치매 60~70% 혈관성치매 30% 루이체치매 10%? 기타치매 ( 뇌손상, 수술, 술, 감염등 ) 혼합형치매 20% 전두측두치매 5%?

5 Alois Alzheimer and Auguste D 5

6 알츠하이머치매병인론 Amyloid hypothesis APP à beta amyloid à plaque formation Tau hypothesis Hyperphosphorylation of tau à Neurofibrillary tangle (NFT)

7 Production of Aβ from APP 7

8 Neuropathology of AD

9 치매의증상 치매의증상 인지기능 C - 집중력 A - 기억력 M - 공간감각 V - 언어기능 L - 전두엽기능 F ( 판단 / 이해 ) 정서 행동 B - 감정 : 흥분, 분노, 우울 -사고: 의심, 망상 ( 도둑, 내집아니다.) -감각: 헛것을보고들음 -행동: 배회, 공격성, 거부, 안절부절

10 Natural History of AD Mini-Mental State Examination (MMSE) Early diagnosis Mild-to-moderate Severe Symptoms Diagnosis Loss of functional independence Behavioural problems Nursing home placement Death Time (years)

11 Structural Imaging for AD Medial temporal atrophy (volumetric MRI) Hippocampus Entorhinal cortex Medial temporal lobe as a whole Medial temporal atrophy (visual rating scale) 11

12 Volumetry for MTA in MCI / AD Hippocampus Entorhinal cortex 12

13 Longitudinal metabolic reductions on FDG-PET FDG-PET scans in a 71-year-old cognitively normal woman at baseline (1989) and over 9 years. During this observation period the patient declined to MCI and later was diagnosed with Alzheimer s disease, which was confirmed at autopsy.

14 FDG-PET and Amyloid PET in AD (PIB: Pittsburgh compound) Klunk WE et al. Ann Neurol Mar;55(3):

15 Course of Aging, MCI and AD Brain Aging AAMI / ARCD Cognitive Decline Brain Aging Brain AD MCI Mild Clinical AD Moderate Moderately Severe Severe Time (Years) 15

16 Criteria for Amnestic MCI Memory complaints, preferably corroborated by an informant Impaired memory function for age and education Preserved general cognitive function Intact activities of daily living Not demented Petersen RC, etc (1999) Arch Neurol 56:

17 Annual Survival Curve of MCI Conversion to AD = 10-15% per year Data from the Mayo Alzheimer's Disease Research Center, Rochester, Minn, which has been observing a group of these subjects for more than 10 years, have demonstrated a conversion to AD of up to 80% during approximately 6 years (Petersen RC, 2001) 17

18 Markers for Progression Amyloid, Tau Metabolism Biomarker Neuroimaging PIB, FDDNP Neuroimaging FDG-PET, fmri Atrophy Cognition Neuroimaging DTI, VBM, SBM Neuropsychology SNSB, MMSE Time Onset of AD

19 CSF Biomarker Concentration L Shaw, J Trojanowski, 2008, ADNI Presentation 19

20 Vascular Dementia Probable VD Dementia CVD : defined by the presence of focal signs on N/E consistent with stroke (with or without Hx of stroke), and evidence of CVD by brain imaging A causal relationship between (1) and (2) inferred by one or more of the following Onset of dementia within 3 months following CVD Abrupt deterioration or stepwise progression Possible VD Dementia and one of the followings CVD defined by the presence of focal signs on N/E without brain imaging studies CVD + No clear temporal relationship between dementia and CVD CVD + subtle onset and variable course of cognitive deficits NINDS-AIREN criteria Roman et al. (1993)

21 Evidence of CVD by Imaging

22 Classification of VCI 22

23 Multi-infarct Dementia: MID Multiple large complete infarcts Cortical or subcortical in location Usually with periphery infarction involving the white matter

24 Strategic Infarct Dementia: SID A single infarct in critical areas Angular gyrus, thalamus, basal forebrain, or territory of the PCA or ACA

25 Subcortical Vascular Dementia Subcortical Vascular Dementia (SVaD) Subcortical Ischemic Vascular Dementia (SIVD)

26 Lacuna, in T2WI and T1WI 26

27 Clinical course of Vascular Dementia Multi-infarct dementia Subcortical vascular dementia Strategic infarct dementia Time

28 Frontotemporal Dementia Clinical Dx criteria: 1) OR 2) 1) Early and progressive change in personality à Frontal variant of FTD 2) Early and progressive change in language, expression of language à Progressive Nonfluent Aphasia severe naming difficulty and problems with word meaning à Semantic dementia Significant impairment in social or occupational functioning Gradual onset and continuing decline in function McKhann et al. (2001) Arch Neurology

29 Frontotemporal lobar degeneration (FTLD) Clinical Syndromes fvftd PNA SD Core diagnostic feature Common feature Early impairment in social conduct Early disinhibition Early emotional blunting Early loss of insight Nonfluent aphasia Fluent but empty aphasia <65 yr & Insidious onset gradual progression Early preservation of memory and orientation Consensus Diagnostic Criteria : Neary et al. (1998) Neurology

31 SD PNFA FTD

32 Dementia with Lewy Bodies Clinical Criteria of DLB Central feature Progressive cognitive decline sufficient to interfere with normal social function Core features: two for probable DLB, one for possible DLB Fluctuating cognition with variations in attention & alertness Recurrent, well-formed and detailed VH Spontaneous parkinsonism Supportive features for Dx Repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, hallucinations in other modalities, REM sleep behavioral disorder, depression McKeith et al. (1996, 1999) Neurology

33 H & E Synuclein(+) cortical Lewy Bodies & Ubiquitin Lewy Neurites

34 Functional Imaging Markers Offers potential insights into all of the main pathological features of AD neuronal loss, tangle and plaque deposition, cholinergic depletion PET: regional glucose metabolism SPECT: cerebral blood perfusion 34

35 Pinpointing plaques with PIB

36 Hemispheric Asymmetry in FTD A B C

37 SPECT and FDG-PET of DLB

38 DDx of Dementia by FDG PET

39 Summary 치매의종류 신경퇴행성질환 알츠하이머병에의한치매 전두측두치매 루이체치매 혈관성치매 MID (Multi-infarct dementia: 다발성경색성치매 ) SVD (Subcortical vascular dementia: 피질하혈관성치매 ) SID (Strategic infarct dementia: 전략적경색치매 ) 기타치매 두부외상, 중독성, 알코올, 대사성등. 조기진단및예방의중요성 : MCI, VCI 병태생리 뇌의각부위의기능과그에따른임상양상 39

Dementia2

Dementia2 Today s Topics Memory Impairment & Dementia Age Associated Memory Impairment Dementia Definition of dementia Depression Schizophrenia Mental retardation Delirium : Not final diagnosis term, but symptomatologic