Nucl Med Mol Imaging Vol. 41, No. 6, Dec 2007 초기단계의피질하혈관성치매와알쯔하이머병에서 Tc-99m HMPAO SPECT 영상소견차이 동아대학교의과대학신경과학교실 1, 핵의학교실 2 박경원 1 강도영 2 박민정 1 천상명 1 차재관 1 김상호 1 김재우 1 Differences of Tc-99m HMPAO SPECT Imaging in the Early Stage of Subcortical Vascular Dementia Compared with Alzheimer's Disease Kyung Won Park, M.D. 1, Do-Young Kang, M.D. 2, Min Jeong Park, M.D. 1, Sang Myung Cheon, M.D. 1, Jae Kwan Cha, M.D. 1, Sang-Ho Kim, M.D. 1, and Jae Woo Kim, M.D. 1 Departments of 1 Neurology and 2 Nuclear Medicine, College of Medicine, Dong-A University, Busan, Korea Purpose: The aim of this study is to assess the specific patterns of regional cerebral blood flow (rcbf) in patients with the early stage of subcortical vascular dementia (SVaD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Materials and Methods: Sixteen SVaD, 46 AD and 12 control subjects participated in this study. We included the patients with SVaD and AD according to NINCDS-ADRDA and NINDS-AIREN criteria. They were all matched for age, education and clinical dementia rating scores. Three groups were evaluated by Tc-99m HMPAO SPECT using statistical parametric mapping (SPM) for measuring rcbf. The SPECT data of patients with SVaD and AD were compared with those of normal control subjects and then compared with each other. Results: SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyri in patients with SVaD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in AD compared with control subjects (uncorrected p<0.01). SVaD patients revealed significant hypoperfusion in the right parahippocampal gyrus with cingulated gyrus, left insula and both frontal subgyral regions compared with AD (uncorrected p<0.01). Conclusion: Our study shows characteristic and different pattern of perfusion deficits in patients with SVaD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness. (Nucl Med Mol Imaging 2007;41(6):530-537) Key Words: subcortical vascular dementia, Alzheimer's disease, statistical parametric mapping analysis, cerebral perfusion SPECT 서 알쯔하이머병 (Alzheimer's disease, AD) 과혈관성치매 (vascular dementia, VaD) 는치매를일으키는원인질환들중가장흔하게발병하는대표적인질환이다. 1,2) 혈관성치매는 Received: 2007. 8. 7. Accepted: 2007. 10. 6. Address for reprints: Do-Young Kang, M.D., Department of Nuclear Medicine College of Medicine, Dong-A University 1, 3-ga Dongdaesin-dong, Seo-gu, Busan 602-715, Korea Tel: 82-51-240-5630, Fax: 82-51-242-7237 E-mail: dykang@dau.ac.kr 이논문은 2005 학년도동아대학교학술연구비 ( 공모과제 ) 지원에의하여연구되었음. 론 알쯔하이머병과달리여러가지다양한혈관성기전과병리학적변화를동반한질환군이며다발성뇌경색치매, 전략적뇌경색치매, 피질하혈관성치매 (subcortical vascular dementia, SVaD) 등과같은몇가지형태의아형들을포함한다. 이중피질하혈관성치매는혈관성치매의아형중에서가장흔하면서상대적으로균일한성질을가지고있다. 3) 뇌의백질과시상및기저핵부위에서의다발성소혈관성변화와열공성뇌경색에의해서발생하고다른아형들과는달리특징적으로잠행성으로발병하여서서히진행하는질병경과를보인다. 4,5) 따라서피질하혈관성치매는임상적으로질병초기에는경도의알쯔하이머병과감별이쉽지않다. 더군다나현재가장많이사용되고있는 DSM-Ⅳ 치매임상진단기준 6) 은기억장애가진단에필수적인요소로되어있기때문에, 상대 530
박경원외. 초기단계의피질하혈관성치매와알쯔하이머병에서 Tc-99m HMPAO SPECT 영상소견차이 적으로기억장애가덜한혈관성치매에이기준을적용할경우진단의정확성이떨어지고, AD병리를가진환자가 VaD 환자군에포함될수있는가능성이높아진다는연구보고들이있다. 7,8) Snowdon 등 9) 이발표한수녀코호트연구에서 AD와혈관성병변은흔하게공존하며, 혈관성병변이 AD 환자의인지기능저하를촉진시키는것으로알려져있다. 치매환자에서양전자방출단층촬영 (PET) 이나단일광자방출단층촬영 (SPECT) 과같은기능적뇌영상법은뇌혈류나뇌대사연구에서광범위하게사용되어왔는데, 알쯔하이머병과혈관성치매질환의기능적이상소견에대한객관적인정보를제공해왔다. 10-13) 그러나시각적분석이나관심영역 (Region of Interest, ROI) 을이용한PET 나 SPECT 뇌영상연구들은검사자의주관적인영향을받아오류가발생할위험이많고검사시간이많이소모된다는단점이있다. 이에비해statistical parametric mapping (SPM) 을이용한분석은 ROI를그리는대신, 영상에서얻는 voxel 볼륨의값을컴퓨터프로그램을이용하여서로직접비교할수있어객관적이고분석의시간이단축된다는장점을가지고있다. 14) AD에서국소뇌혈류장애소견은질병초기에양측의마루-관자부위의저관류를보이고질병후기에는이마엽부위로의저관류부위가확산되는것이특징으로알려져있다. 15-17) 이에비해피질하혈관성치매에서의특징적인국소뇌혈류분포양상은연합및일차피질부위, 시상, 기저핵, 그리고소뇌부위등다양한부위에서의저관류소견이라고할수있다. 18) 또한이마엽띠이랑혹은상부이마엽이랑 (superior prefrontal gyrus) 등을포함한이마엽부위에현저한저관류를보이는것이특징이다. 11,17,19,20) 그러나이러한국소뇌혈류분포양상은두질환에서서로중복되어나타나는경우가많고, 일반적인국소뇌혈류 SPECT 영상분석방법으로알쯔하이머병과피질하혈관성치매를정확히감별진단하기에는한계가있다. 15,21) 저자들은 Tc-99m SPECT 영상소견의 SPM분석을이용하여질병초기의피질하혈관성치매환자의뇌관류장애부위와특징을밝히고, 경증알쯔하이머병환자와비교하여구체적인저관류부위를알아내어두질환의국소뇌혈류분포의차이를비교하고자하였다. 대상및방법 1. 대상 2004년 3월부터 2004년 9월까지동아대학교병원신경과기억장애및치매클리닉을통하여피질하혈관성치매로진단받은환자 16명과알쯔하이머병으로진단받은환자 46 명, 정상대조군 12명을대상으로하였다. 알쯔하이머병환자군과혈관성치매환자군은나이와교육수준, 그리고치매의정도차이가없도록하였다. 치매의정도는한국형간이정신상태검사 (Korean version of mini-mental state examination, K-MMSE) 22) 와치매임상평가척도 (Clinical dementia rating, CDR) 23) 를사용하여평가하였다. 피질하혈관성치매환자는 DSM-Ⅳ 진단기준 6) 을만족하고, National Institute of Neurological Disorders and Stroke and l'association Internationale pour la Recherche et l'enseignement en Neurosciences (NINDS-AIREN) 의 probable 혹은 possible 진단기준 24) 을만족하는환자들중광범위한융합성의 (confluent) 양측뇌실주위허혈성백질변성을보이거나피질하부위에다발성의열공성뇌경색을보이는환자들로정하였다. 이들환자중 MRI에서열공성뇌경색이나백질변성이외의피질성뇌경색이나구조적이상을보이는경우에는대상환자에서제외하였다. 알쯔하이머병환자는 Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-Ⅳ) 의치매정의APA 6) 를만족하고, National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association (NINCDS-ADRDA) 의 probable AD의진단기준 25) 을만족하는경우로하였다. 모든환자군에서 CT나 MRI에서뇌종양이나감염및기타질환이발견된경우, 과거력에서우울증, 두부손상, 약물남용, 갑상선기능이상이나기타인지기능에장애를줄수있는내과적인문제가있는경우들은연구에서제외하였다. 기능적뇌영상검사의정상대조군은건강증진센터나신경과외래를통해서모집된정상인을대상으로하였다. Christensen 26) 이정한인지기능에영향을미치는 28가지의질환이없고, 환자나보호자에의해기억장애나기타인지기능저하가없다고확인된건강한자를대상으로하여 50대부터 80대까지 12명을선정하였다. 2. 방법 1) 단일광자방출단층촬영 (SPECT) 정상대조군과대상환자군을대상으로 SPECT 는 Tc-99m HMPAO 925 MBq를정맥주사하고 5분째영상을얻었다. Fanbeam 조준기가부착된이중헤드감마카메라 (MultiSPECT II, ICON, Siemens, USA) 를사용하여투사당 20-25초씩 128*128 매트릭스로총 120개의투사상을얻었다. 여과기를사용하여여과후역투사방법으로재구성하고 Chang의방법 27) 으로감쇠보정을하였고횡단면과관상면, 그리고시상면을각각얻었다. 531
Kyung Won Park, et al. Differences of Tc-99m HMPAO SPECT Imaging in the Early Stage of Subcortical Vascular Dementia Compared with Alzheimer's Disease Table 1. Demographic Data and General Cognitive Functions in SVaD and AD Groups and Control Subjects Sex (male/female) Age (yr) Education (yr) K MMSE scores CDR SVaD (n=16) AD (n=46) Control (n=12) p value 10/6 68.0±7.0 6.3±5.6 20.6±4.0 0.8±0.3 16/30 69.9±7.4 5.4±4.7 19.0±3.6 0.9±0.2 3/9 67.1±5.3 6.2±4.2 26.0±2.1 ND *p < 0.05, Values are mean (SD) SVaD; subcortical vascular dementia, AD; Alzheimer s disease, CDR; clincial dementia rating, K-MMSE; Korean version of mini mental state examination, ND; not done ND 0.428 0.740 0.851 0.340 Table 2. Areas with Significantly Reduced rcbf in SVaD Patients in Comparison to the Normal Control Brain region Talairach coordinates: x, y, z (mm) Z-score Right parahippocampal gyrus Right cingulated gyrus Right frontal subgyral white matter Right transverse temporal gyrus Right parietal subgyral white matter Right thalamus Left insula Left cingulate gyrus Left superior temporal gyrus Left caudate nucleus Left forntal subgyral white matter 24 16 30 42 30 8-46 -12-48 -14-22 rcbf; regional cerebral blood flow, SVaD; subcortical vascular dementia -35-33 -33-27 -39-13 -19 9-33 5 5-3 35 35 12 33 14 14 29 9 15 22 4.71 4.10 3.77 3.56 3.47 3.43 3.92 3.78 3.31 3.13 2.90 Figure 1. SPM analysis results show areas with decreased regional cerebral blood flow in patients with SVaD in comparison to control subjects (uncorrected p<0.001). 532
박경원외. 초기단계의피질하혈관성치매와알쯔하이머병에서 Tc-99m HMPAO SPECT 영상소견차이 Table 3. Areas with Significantly Reduced rcbf in Patients with AD in Comparison to the Normal Control Brain region Talairach coordinates: x, y, z (mm) Z score Right Cingulate gyrus Right Fusiform gyrus Left Posterior Cingulate gyrus Left Supramarginal gyrus Left Superior Temporal gyrus Left Postcentral gyrus Left Anterior Cingulate gyrus Left Inferior parietal lobule 10 50-18 -55-50 -57-8 -51 p<0.001, uncorrected rcbf; regional cerebral blood flow, AD; Alzheimer s disease -37-57 -56-47 -33-21 19-43 35-12 12 24 7 42 23 41 2.93 2.56 3.91 3.15 3.08 2.89 2.66 2.43 2) Statistical parametric mapping 분석감마카메라에서얻은영상파일을 DICOM 3.0 파일포맷으로변환후 MRIcro (Windows 95 이상 ) 프로그램을이용하여데이터를헤더정보와영상정보를분리하여 Analyze 파일포멧으로변환하여 Matlab version 6.0 (Mathworks, Inc., Natick, USA) 을기반으로한 SPM99 (Institute of Neurology, University College of London, UK) 프로그램에서영상분석을하였다. SPM99 분석으로얻은결과는평균 MR template (Montreal Neurological Institute, McGill University, Canada) 14) 위에얹어서횡단면, 시상면으로표현하여뇌혈류의변화를알아볼수있게하였다. 알쯔하이머병 환자들의자료는 SPM 분석에서소뇌에대한 count normalization 과정을거쳤다. SPM 분석의결과는 p 값을 uncorrected 0.001, uncorrected 0.01 로변화시키면서의미있는결과를찾았고최소 50개이상의활성화된화소를보이는영역만을분석하였다. 뇌표준지도위에덧씌워진결과들의정확한해부학적위치를알기위하여각화소의 x, y, z 값을 Talairach Daemon Database 소프트웨어에넣어서최종적으로각영역의해부학적위치들을구하였다. Tc-99m HMPAO SPECT 뇌영상이미지분석은정상대조군과피질하혈관성치매군, 정상대조군과알쯔하이머병 Figure 2. SPM analysis results show areas with decreased regional cerebral blood flow in patients with AD in comparison to control subjects (uncorrected p<0.001). 533
Kyung Won Park, et al. Differences of Tc-99m HMPAO SPECT Imaging in the Early Stage of Subcortical Vascular Dementia Compared with Alzheimer's Disease Table 4. Areas with Significantly Reduced rcbf in SVaD Patients in Comparison to AD Brain region Talairach coordinates: x, y, z (mm) Z-score Right Parahippocampal gyrus Right Parietal sublobar white matter Right Frontal subgyral white matter Right Cingulate gyrus Right Thalamus Left Insula Left Frontal subgyral white matter p<0.001, uncorrected rcbf; regional cerebral blood flow, AD; Alzheimer's disease, SVaD; subcortical vascular dementia 24 30 24 16 6-42 -20-35 -49 18 15-9 -15 7-3 25 19 29 8 12 31 3.67 3.54 3.51 3.42 3.38 3.07 3.03 군을각각비교하였고, 다음단계로알쯔하이머병군과비교하여피질하혈관성치매군의저관류부위를분석하였다. 의미있는저관류부위는 SPM99 로분석하여그결과를 3차원칼라영상과 MRI 표준지도로각각표시하였다. 결과 피질하혈관성치매군, 알쯔하이머병군, 그리고정상대조군의평균연령은각각 68.0±7.0세, 69.9±7.4세, 67.1±5.3세였다. 교육수준은각각 6.3±5.6년, 5.4±4.7년, 6.2±4.2년이었다. 한국형간이정신상태검사 (K-MMSE) 22) 점수는피질하혈 관성치매군알쯔하이머병군, 그리고정상대조군에서 20.6 ±4.0점, 19.0±3.6점, 26.0±2.1점이었으며, 치매임상평가척도 (CDR) 23) 점수는피질하혈관성치매군과알쯔하이머병군에서각각 0.80±0.26, 0.86±0.23 이었다. 세대상군간에나이와교육수준에서통계적으로유의한차이를보이지않았고, 피질하혈관성치매군과알쯔하이머병군에서사이에나이, 교육수준, K-MMSE, 그리고 CDR에서의미있는차이를보이지않았다 (p>0.05, Table 1). 정상대조군에비해피질하혈관성치매군의저관류부위는우측해마이랑 (parahippocampal gyrus), 뇌섬엽 (left insula), 관자엽이랑 (right transverse temporal gyrus), 마루 Figure 3. SPM analysis results show areas with decreased regional cerebral blood flow in patients with SVaD in comparison to those of AD (uncorrected p<0.01). 534
박경원외. 초기단계의피질하혈관성치매와알쯔하이머병에서 Tc-99m HMPAO SPECT 영상소견차이 엽소이랑백질 (right parietal subgyral white matter), 시상 (right thalamus) 과좌측상관자옆이랑 (superior temporal gyrus), 꼬리핵 (caudate nucleus), 그리고양측띠이랑 (cingulate gyri) 과이마엽소이랑백질 (frontal subgyral white matter), 부위였다 (uncorrected p<0.001, Table 2, Fig. 1). 정상대조군에비해알쯔하이머병환자군의저관류부위는좌측모서리위이랑 (left supramarginal gyrus), 상부관자이랑 (superior temporal gyrus), 중심뒤이랑 (postcentral gyrus), 하부마루소엽 (inferior parietal lobule) 과우측뒤통수관자이랑 (fugiform gyrus) 그리고양측띠이랑 (cingulate gyri) 부위였다 (uncorrected p<0.001, Table 3, Fig. 2). 알쯔하이머병군에비해피질하혈관성치매군의저관류부위는우측해마이랑 (right parahippocampal gyrus) 과띠이랑 (cingualte gyrus), 좌측뇌섬엽 (left insula), 그리고양측이마소이랑백질 (both frontal subgyral white matter) 부위였다 (uncorrected p<0.01, Table 4, Fig. 3). 이상의결과를요약하면알쯔하이머병군에비해피질하혈관성치매군에서는이마관자엽부위와시상, 그리고마루엽의중심뒤이랑 (postcentral gyrus) 에비대칭적으로산재되어저관류부위가관찰되었다. 고찰 임상적특징과인지기능장애양상을이용하여알쯔하이머병과혈관성치매를구분하려는시도는그동안여러연구자들에의해다양하게있어왔다. 28,29) 두질환의구별이중요한것은치료방침이다르고병의경과와예후에있어서많은차이가나기때문이다. 일반적으로혈관성치매의경우갑자기발병하면서계단식경과를가지는것으로알려져있다. 그러나열공성뇌경색 (Lacunar state) 과 Bingswanger's disease 를포함하는비교적동질성을가진질환군으로서 3) 혈관성치매의가장흔한아형중하나인피질하혈관성치매는임상적으로잠행성으로시작하여서서히악화되는알쯔하이머병과비슷한진행과정을가진다. 11) 따라서질병초기에는임상경과와인지기능장애양상만으로두질환을정확히구분하기어려워서초기진단을내린후치료계획을세우고예후를판정하기가쉽지않다. 따라서알쯔하이머병과혈관성치매환자의진단과진행정도판정에있어서기능적뇌영상검사의필요성이최근에더욱대두되고있다. PET이나 SPECT 를이용한기능적뇌영상검사는각종치매환자의국소뇌혈류나뇌대사의정도를측정하고분포를제공하여임상적인원인질환을진단하고치매정도를평가하며, 치료의결과를판정하는데유용한검사로알려져 있다. 13,30) 뇌미세혈관병증 (cerebral microangipathy) 환자에서인지기능장애의정도는MRI에서관찰되는열공성뇌경색이나백질변성의심한정도보다는기능적뇌영상검사에서관찰되는저관류나저대사의정도와상관관계가있다는연구결과 12) 는치매질환에서기능적뇌영상검사의상대적인중요성과필요성을강조하고있다. PET이나 SPECT를이용하여실시되었던대부분의기능적연구들은영상위에직접 ROI를구해서뇌혈류나뇌대사분포를측정하였는데, 여기에는몇가지제한점이있다. 첫째, ROI를그리는데시간이많이걸린다. 둘째, ROI를그리는부위를선정하는데있어검사자의편견이작용한다. 셋째, 뇌혈류감소가있지만그영역의크기가작은경우에는큰 ROI에묻혀서의미가희석될수있다. 넷째, ROI 밖에위치하는뇌혈류감소부위는분석에서제외될수있다. 13) 이런제한점을극복하기위해 Friston 등 14) 은 SPM 분석방법을개발하여 3차원이미지데이터전체를 voxel 대 voxel 로비교하면서통계적인분석을하여전체데이터에대한보다객관적인분석을가능하게하였다. 본연구는이전에수행되었던선행연구의제한점을보충하고극복하기위해대상환자를 SVaD 에국한하여동질성그룹으로대상을한정하였고, 치매정도를 CDR 1 이하로제한하여경증의환자를대상으로하였다. SVaD 에서일반적인국소뇌혈류분포는주로이마엽, 관자엽그리고마루엽등의피질부위와시상과기저핵을포함하는피질하부위에서비대칭적이고다발성의저관류소견과전띠이랑과상부앞이마엽이랑을포함하는이마엽부위에국한된관류저하가특징으로알려져있다. 11,18-20) SVaD 에서피질부위에혈류감소가일어나는기전은피질하부위에존재하는뇌허혈성병변이피질과피질하구조를단절시켜피질부위의당대사저하를야기하고이로인해이차적으로혈류저하가일어나는것으로설명하고있다. 31) 본연구의 SVaD 군에서정상대조군과비교해서양측내측이마엽과양측관자엽부위, 그리고우측시상및좌측꼬리핵 (caudate nucleu) 부위에서저관류가나타났고, AD군과비교해서는양쪽관자엽과양측이마부위백질부위에현저한저관류소견을보였고, 우측띠이랑과우측시상에서관류저하소견이관찰된것은기존연구결과 11,18-20) 와비교적일치하였다. 다만 SVaD 군에서우측마루엽이 AD군에비해저관류부위로나타난것은다소의외의결과라고할수있다. 정확한이유를알수는없으나몇가지요인들에의해영향을받은것으로보인다. 우선단일대학병원의신경과에서일정한기간을통해서모집된환자들만을대상으로 AD와 SVaD 로진단하고분류하는과정에서선택오류 535
Kyung Won Park, et al. Differences of Tc-99m HMPAO SPECT Imaging in the Early Stage of Subcortical Vascular Dementia Compared with Alzheimer's Disease (selection bias) 가발생했을가능성이있다. 둘째, 연구대상환자들의특성에의해서연구결과가영향을받았을것으로생각된다. 즉, AD와 SVaD 의특징을동시에가지고있는혼합성치매환자가 SVaD 군에많이포함되어서 SPM 분석시마루엽부위에저관류가관찰된것으로생각할수있다. 세번째로는, 혈관성치매군이상대적으로이질적이고다양한병인을가지고있기때문에알쯔하이머병환자군에비해혈류저하소견이예상치못한부위에서도나타났다고생각할수있다. 본연구의제한점은대상환자군의수가고르지못했다는점을들수있다. AD 환자수에비해 SVaD 환자와정상대조군의수가 1/3 정도였으므로결과분석시통계적유의성을얻기에제한점이있다고할수있다. 그러나다양한혈관성병인을가진 VaD 의여러아형중가장균일한환자군이라고할수있는 SVaD 환자군만을대상으로정상대조군과 AD 환자군을비교분석하여기능적뇌영상소견의차이점을규명하고객관적인영상데이터를제시한점은다른연구들과비교하여분명한차이점을보여주고있다. 요약 목적 : 본연구는초기의피질하혈관성치매와알쯔하이머병환자에서 Tc-99m HMPAO 단일광자방출단층촬영술을이용하여국소뇌혈류흐름의특징적인양상을평가하고두질환에서의차이를비교하고자하였다. 대상및방법 : 피질하혈관성치매환자 16명, 알쯔하이머병 46명, 12명의대조군이포함되었다. 피질하혈관성치매와알쯔하이머병은 NINCDS-ADRDA 와 NINDS-AIREN 기준에합당하였고, 이들의연령, 교육연수, 한국형간이정신상태검사점수와치매임상척도점수를일치시켰다. 세군에서국소뇌혈류흐름을측정하고자 SPM 분석을이용한 Tc-99m HMPAO 단일광자방출단층촬영술을실시하였다. 피질하혈관성치매와알쯔하이머병에서의단일광자방출단층촬영술결과를정상대조군과비교하였고, 이어서두질환간의차이를비교하였다. 결과 : 대조군과의 SPM 분석결과피질하혈관성치매에서는우측관자엽, 시상, 좌측뇌섬엽, 상부관자이랑, 양측띠이랑, 이마엽에서의미있는관류저하가있었고, 알쯔하이머병에서는좌측모서리위이랑, 상부관자이랑, 중심뒤이랑, 하부마루소엽, 우측뒤통수관자이랑, 양측띠이랑에서관류저하을보였다 (uncorrected p<0.01). 피질하혈관성치매환자에서알쯔하이머병환자에비해우측해마이랑, 띠이랑, 좌측뇌섬엽, 양측이마소이랑부위에의미있는관류저하를보였다 (uncorrected p<0.01). 결론 : 본연구는피질하혈관 성치매와알쯔하이머병환자에서의관류의특징과차이를보여주었고, 이러한결과는질병의초기단계에서두질환을구별하는데도움을줄수있을것으로생각한다. References 1. Terry RD, Katzman R. Senile dementia of the Alzheimer type. Ann Neurol 1983;14:497-506. 2. Kim DH. Epidemiology of dementia in Korea. J Korean Med Assoc 2002;45:356-60. 3. Erkinjuntti T. Subcortical vascular dementia. Cerebrovasc Dis 2002; 13 Suppl 2:58-60. 4. Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-36. 5. Erkinjuntti T, Rockwood K. Vascular dementia. Semin Clin Neuropsychiatry 2003;8:37-45. 6. Association AP. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press. 1994. 7. Bowler J.V. HV. Current criteria for vascular dementia-a critical appraisal. In: Bowler J.V. HV, ed. Vascular cognitive impairment. Oxford: Oxford University Press, 2003:1-11. 8. Erkinjuntti T, Roman G, Gauthier S, Feldman H, Rockwood K Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke 2004;35:1010-7. 9. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997;277:813-7. 10. Neary D, Snowden JS, Shields RA, Burjan AW, Northen B, MacDermott N et al. Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia. J Neurol Neurosurg Psychiatry 1987;50:1101-9. 11. Starkstein SE, Sabe L, Vazquez S, Teson A, Petracca G, Chemerinski E et al. Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease. Stroke 1996;27:408-14. 12. Herholz K. FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord 1995;9:6-16. 13. Jagust W, Thisted R, Devous MD Sr, Van Heertum R, Mayberg H, Jobst K. et al. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study. Neurology 2001;56: 950-6. 14. Friston KJ. Statistical parametric mapping. Functional Neuroimaging. San Diego: Academic Press, 1994:79-93. 15. Mielke R, Pietrzyk U, Jacobs A, Fink GR, Ichimiya A, Lessler J et al. HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern. Eur J Nucl Med 1994;21:1052-60. 16. Muller H, Moller HJ, Stippel A, Fric M, Grunwald F, Laux G et al. SPECT patterns in probable Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 1999;249:190-6. 17. Tohgi H, Yonezawa H, Takahashi S, Sato N, Kato E, Kudo M et al. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes. Neuroradiology 1998;40:131-7. 18. Talbot PR, Lloyd JJ, Snowden JS, Neary D, Testa HJ A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia? J Neurol Neurosurg Psychiatry 1998;64:306-13. 19. Shyu WC, Lin JC, Shen CC, Hsy YD, Lee CC, Shiah IS et al. 536
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