Neuroimaging findings in vascular dementia

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1 Neuroimaging findings in vascular dementia 충남의대신경과학교실이애영 Introduction 혈관치매 (vascular dementia, VaD) 는알쯔하이머병다음으로흔한치매이다. 혈관치매를진단하기위하여임상진단기준과신경영상을이용하여진단정확성을높일수있다 (Table1)[1, 2]. 혈관치매에이용되는신경영상은뇌혈관질환의유무를확인하고병변의위치와정도에대한정보를제공한다. 또한치매를일으키는구조적뇌이상 ( 예, 정상뇌압수두증, 만성경막하출혈, 뇌종양 ) 을감별하게해준다. 치매검사를받는환자의약 5% 정도에서이런뇌의구조적이상을임상적으로미리의심하지못했으나신경영상을시행하여발견할수있다 [3]. 또한치매진단에활용되는신경영상의유용성을평가한결과뇌영상촬영후환자의 19~28% 에서진단이바뀌었고 15% 에서치료방법이변경되었으므로미국신경과학회에서는치매에대한검사를처음받는환자라면반드시신경영상촬영을하도록추천하고있다 [4]. Table 1. NINDS-AIREN criteria for probable vascular dementia 기준내용 치매 뇌혈관질환 ( 다음중한가지 ) 치매와뇌혈관질환의시간적관련성 기억을포함한인지기능저하로독립적인일상생활에장애가있는상태 뇌졸중기왕력 진찰상국소신경학적징후 ( 기왕력은있을수도있고없을수도있음 ) CT/MRI 로뇌졸중병변확인 뇌졸중발병 3 개월내에치매가생긴경우 인지기능이갑자기저하된경우 인지수준에변동이있고계단식으로떨어지는경과를보이는경우 (Fluctuating, stepwise progression of cognitive deficits) Pathophysiology 혈관치매는혈관병변의원인 ( 뇌혈관질환과혈관위험인자 ), 뇌병변 ( 뇌경색, 백질변성, 뇌위축 ), 그리고환자가가진개별적인차이 ( 나이, 교육정도, 생활방식등 ) 에의하여종합된결과이다 ( 그림 1)[1]. 혈관치매를초래하는위험인자는조절불가능한요인과조절가능한요인으로분류할수있다 (Table 2). Table 2. Risk factors for vascular dementia 위험인자내용 조절불가능 조절가능 노화유전적소인 ( 피부색또는인종의차이포함 ) 뇌졸중기왕력낮은교육수준고혈압, 당뇨, 고지혈증관상동맥질환, 심방세동흡연 1

그러나신경영상을보고혈관치매를진단할수있는결정적인지표는없으며임상소견과의연관성을찾는것이중요하다.

2 Figure 1. Pathophysiology of vascular dementia, two different schematic representations. 신경영상의역할 CT 나 MRI 가혈관치매의진단에필요하며특히 MRI 가병변의특징, 위치, 정도를평가하는데더유용하다 [5]. CT 나 MRI 상뇌혈관병변이없으면혈관치매를감별진단에서제외할수있고알쯔하이머병과구분하는데가장중요한소견으로여겨진다. 그러나신경영상을보고혈관치매를진단할수있는결정적인지표는없으며임상소견과의연관성을찾는것이중요하다. 임상적으로혈관치매진단에이용하는신경영상진단기준의적용은영상을보는의사의경험과지식에따라차이를보일수있지만일반적으로병변의위치와정도, 뇌위축및백질변성등을종합적으로고려해야한다 [6] Table 3. Brain imaging lesions associated with vascular dementia Topography Radiological lesions associated with dementia include any of A. Largevessel Bilateral ACA strokes in the PCA, including paramedian thalamic or medial temporal lobe lesions 2

the following or combinations thereof: following territories B.

or more lacunes in the BG & 2 or more lacunes in the FWM) Severity In addition to the above, A.

Leukoencephalopathy involving at least 25% of the total WM (beginning to include: become confluent in four regions, i.e., frontal bilaterally, and parietal bilaterally) PT, parietotemporal; TO,

3 the following or combinations thereof: following territories B. Smallvessel diseases MCA, including PT, TO, and/or angular gyrus Watershed carotid territories: bilateral superior frontal, PO and/or deep and superficial MCA Multiple BG & FWM lacunae (must be two or more lacunes in the BG & 2 or more lacunes in the FWM) Severity In addition to the above, A. Large-vessel lesions of the dominant hemisphere relevant radiological lesions associated with dementia B. Bilateral large-vessel hemispheric strokes C. Leukoencephalopathy involving at least 25% of the total WM (beginning to include: become confluent in four regions, i.e., frontal bilaterally, and parietal bilaterally) PT, parietotemporal; TO, temporooccipital; PO, parietooccipital; BG, basal ganglia; FWM, frontal white matter Arterial territorial infarct 대혈관다발경색 (multiple large-vessel infarcts) 에의한경우나인지기능수행에전략적으로중요한위치에생긴단일경색 (single strategic infarct) 때문에혈관치매가생길있다 ( 그림 2). 단일경색에의하여치매가생길수있는전략적위치로 angular gyrus, thalamus, basal forebrain, posterior or anterior cerebral artery 영역등이있다 [6]. Figure 2. Multiple large-vessel infarct; thalamic infarcts, both; angular gyrus infarct Small-vessel disease 백질변성과열공경색이대뇌소혈관질환의지표가된다 [7]. 열공경색의수가많거나백질변성이 10 cm 2 이상인경우인지기능저하가발생하기쉽다 [7, 8]. 노인의신경영상에서보이는백질변성의임상적의미와병리학적소견에대하여이견이많은상태이다 [9]. 백질변성은혈관치매에서많이관찰되지만정상노인이나알쯔하이머병환자에서도뇌실주변에좌우대칭적으로관찰할수있다 [10]. 이는고혈압과노화에의하여미세동맥에동맥경화성변화 (arteriosclerotic changes) 가초래되어관류저하와허혈이생겨서백질에광범위하고미만성변화가나타나며전체대뇌백질의 25% 이상침범되면혈관치매발생가능성이높다 [11]. 열공경색은 2 cm 미만의작은경색이심부피질에생기는것으로증상을보일수도있지만무증상인경우가더흔하다 [12]. 이런열공경색은혈관주위공간이늘어나면서생긴 Virchow-Robin space 와감별이필요한데 MRI 영상의종류와관계없이뇌척수액음영과동일하거나위치가 basal ganglia inferior 1/3 이나 anterior commissure 바깥에위치한경우, 모양이둥글거나난원형인경우, 그리고크기가 3 mm 미만인경우라면 Virchow-Robin space 일가능성이높다 [13]. 대뇌백질변성과열공경색이전두엽 - 피질하경로 (frontal cortico-subcortical circuit) 에손상을주어유창성과집행기능장애가나타나며 basal forebrain 에위치한 Mynert 기저핵으로부터생성된아세틸콜린이대뇌피질로전달되는경로를차단하여콜린부족이발생하는것이혈관치매에콜린분해효소차단제사용의근거가된다 ( 그림 3)[14, 15]. 3

4 Figure 3. Topography of lacunar infarction and white matter changes corresponding upon the cholinergic trajectories. Amyloid angiopathy 아밀로이드혈관병증은유전성혈관질환이다 [16]. 한개또는여러개의비외상성엽상출혈 (lobar hemorrhage) 이전두엽, 두정엽, 측두엽그리고후두엽의순서로많이생긴다 [17]. 산발적으로생기는아밀로이드혈관병증은엽상출혈외에대뇌피질이나피질아래에점상출혈이관찰되며급속하게진행하는치매를유발한다. Gradient-echo MRI 영상에서병변의 magnetic susceptibility 때문에저음영소견으로잘관찰된다 ( 그림 4)[18] Figure 4. AMyloid angiopathy. Axial spin-echo T2-weighted MR image shows large frontal hemorrhage and another small punctate hypointense lesions, best seen on axial gradient-echo T2-weighted MR image. 4

Figure 5. Pathophysiology and clinical features of the small-vessel disease. 양전자방출단층촬영 (Positron emission tomography) 을알쯔하이머병을비롯한다른종류의치매와혈관치매를구분하기위하여사용할수있다.

또한알쯔하이머병과같이있는혼합치매 (mixed dementia) 의경우진단적어려움은훨씬커서자세한병력청취, 체계적인신경학적진찰, 그리고신경영상을적용하여도실제보다적은진단율을보이는경우가많다. 그럼에도 NINDS-AIREN 혈관치매진단기준의진단특이도는 91% 정도로신뢰할만하며신경영상을적용하여알쯔하이머병의가능성을배제할수있다.

5 Figure 5. Pathophysiology and clinical features of the small-vessel disease. 양전자방출단층촬영 (Positron emission tomography) 을알쯔하이머병을비롯한다른종류의치매와혈관치매를구분하기위하여사용할수있다. 전형적으로두정엽과측두엽에대칭적인대사저하를보이는알쯔하이머병과는달리혈관치매는전형적인소견은없으며혈관병변의위치에따라국소적인대사저하가나타난다. Conclusion 혈관치매는임상적으로매우흔하지만임상진단기준이나신경영상특징이기저질환이나환자개인의특성에따라매우다양하여진단이쉽지않다. 또한알쯔하이머병과같이있는혼합치매 (mixed dementia) 의경우진단적어려움은훨씬커서자세한병력청취, 체계적인신경학적진찰, 그리고신경영상을적용하여도실제보다적은진단율을보이는경우가많다. 그럼에도 NINDS-AIREN 혈관치매진단기준의진단특이도는 91% 정도로신뢰할만하며신경영상을적용하여알쯔하이머병의가능성을배제할수있다. 혈관치매진단을위하여시행하는신경영상을통하여임상증상과일치하는뇌졸중병변을확인하고무증상병변, 백질변성, 대뇌위축, 뇌실확장등을평가할수있다. 신경영상을시행하여뇌혈관질환과치매발생사이의인과관계및시간적연관성을판단할수있으며이를통하여혈관치매를조기진단하고적절한치료를하는지침을마련할수있다. References 1. Roman GC, Erkinjuntti T, Wallin A, Pantoni L. Chui HC. Subcortical ischemic vascular dementia. Lancet Neurol 2002;1: Erkinjuntti T. Clinical criteria for vascular dementia: the NINDS-AIREN criteria. Dementia 1994;5: Chui H, Zhang Q. Evaluation of dementia: a systematic study of the usefulness of the American Academy of Neurology s practice parameters. Neurology 1997;49: Knopman DS, DeKosky ST, Cummings JL, Chui HC, Corey-Bloom J, Relkin N, et al. Practice 5

6 parameter: Diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommitte of the American Academy of Neurology. Neurology 2001;56: Scheltens P, Fox N, Barkhof F, De Carli C. Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusiom. Lancet Neurol 2002;1: Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43: Schmidt R, Schmidt H, Fazekas F. Vascular disk factors in dementia. J Neurol 2000;247: Boone KB, Miller BL, Lesser IM, Mehringer CM, Hill-Gutierrez E, Goldberg MA, et al. Neuropsychological correlates of white matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol 1992;49: De Groot JC, de Leeuw FE, Oudkert M, Hofman A, Jolles J, Breteler MM. Cerebral white matter lesions and subjective cognitive dysfunction. The Rotterdam Scan Study. Neurology 2001;56: Barber R, Scheltens P, Gholkar A, Ballard C, McKeith I, Ince P, et al. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer s disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry 1999;67: Schletens P, Erkinjuntti T, Wahlund LO, Inzitari D, del Ser T, Pasquier F, et al. White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes. Eur Neurol 1998;39: Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR. Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol 1998;55: Song CJ, Kim JH, Kier EL, Bronen RA. MR imaging and histologic features of subinsular bright spots on T2-weighted MR images: Virhcow-Robin spaces of the extreme capsule and insular cortex. Radiology 2000;214: Selden NR, Gitelman DR, Salamon-Murayama N. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998;121: Swartz RH, Sahlas DJ, Black SE. Strategic involvement of cholinergic pathways and executive dysfunction: Does location of white matter signal hyperintensities matter? J Stroke Cerebr Vascular Dis 2003;12: Weller RO, Preston SD. The spectrum of vascular disease in dementia. From ischemia to amyloid angiopathy. Adv Exp Med Biol 2001;487: Good VD, Ng VW, Clifton A, Britton JA, Hart Y, Wilkins P. Amyloid angiopathy causing widespread military hemorrhage within the brain evident on MRI. Neuroradiology 1998;40: Hendricks HT, Franke CL, Theunissen PH. Cerebral amyloid angiopathy: diagnosis by MRI and brain biopsy. Neurology 1990;40:

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

치매의종류와병태생리 - 간호협회치매인력양성교육 울산의대, 서울아산병원 정신과김성윤 1 Contents 치매의종류 신경퇴행성질환 알츠하이머병에의한치매 전두측두치매 루이체치매 혈관성치매 MID (Multi-infarct dementia: 다발성경색성치매 ) SVD (Subcortical vascular dementia: 피질하혈관성치매 ) SID (Strategic