untitled

Transcription

1 원저 J Korean Neurol Assoc / Volume 24 / August, 2006 알츠하이머병과혈관성치매에서의진행정도에따른임상양상의차이 김해한솔요양병원, 경성대학교사회복지학과 a, 인제대학교의과대학신경과학교실 b, 동아대학교의과대학신경과학교실 c, 부산의료원신경과 d, 신라대학교가족학과 e, 고신대학교의과대학신경과학교실 f, 성균관대학교의과대학마산삼성병원신경과 g, 마산태봉병원신경과 h, 동의의료원신경과 i, 성균관대학교의과대학사회의학교실 j, 메리놀병원 k 김태유김수영 a 김응규 b 김재우 c 박경원 c 성상민 d 손태홍 e 안경숙 a 유봉구 f 윤수진 g 윤성민 h 이상찬 i 정해관 j 최문성 k 홍태용부산 경남치매학회 The Differences of Clinical Features between Alzheimer's Disease and Vascular Dementia According to Progression Tae-You Kim, M.D., Soo Young Kim, Ph.D. a, Eung-Gyu Kim, M.D. b, Jae Woo Kim, M.D. c, Kyung Won Park, M.D. c, Sang Min Sung, M.D. d, Taehong Sohn, Ph.D. e, Kyung-Sook Ann, Ph.D. a, Bong-Goo Yoo, M.D. f, Soo Jin Yoon, M.D. g, Sung Min Yoon, M.D. h, Sang Chan Lee, M.D. i, Hae-Kwan Cheong, M.D. j, Mun Seong Choi, M.D. k, Tae-Yong Hon, M.D., Busan Gyeongnam Dementia Association Department of Neurology, Gimhae Hansol Hospital, Gimhae; Department of Social Welfare, Kyung Sung University a, Busan; Department of Neurology, Inje University College of Medicine b, Busan; Department of Neurology, Dong-A University College of Medicine c, Busan; Department of Neurology, Busan Medical Center d, Busan; Department of Family Stuides, Silla University e, Busan; Department of Neurology, Kosin University College of Medicine f, Busan; Department of Neurology, Sungkyunkwan University College of Medicine, Masan Samsung Hospital g, Masan; Department of Neurology, Masan Taebong Hospital h, Masan; Department of Neurology, Dong-eui Medical Center i, Busan; Department of Social and Preventive Medicine, School of Medicine, Sungkyunkwan University j, Suwon; Department of Neurology, Maryknoll Hospital k, Busan, Korea Background: The differences in clinical features are important when differentiating between Alzheimer's disease (AD) and vascular dementia (VD). There have been many studies comparing the severity of progression in both diseases. They have assessed individual symptoms but have not explained the differences and global change of progression comprehensively. We have evaluated the cognitive and non-cognitive functions at the same time and evaluated the differences between AD and VD. Methods: One hundred and thirty-eight dementia patients from Busan Gyeongnam Dementia Association outpatient clinics were analyzed. All of the patients underwent the Korean version of the Mini-Mental State Examination (K-MMSE), the expanded version of the Korean Clinical Dementia Rating Scale (CDR), the Korean version of the Neuropsychiatric Inventory (K-NPI), the scales for activity of daily living, and the Short form of the Samsung Dementia Questionnaire (S-SDQ). Results: There were 93 patients with AD and 45 with VD. VD patients revealed more severe Barthel Index of Activity of Daily Living (B-ADL) deficits. AD patients had more severe memory and orientation deficiency in CDR 1 and CDR 2. VD patients revealed much faster decline of K-MMSE score between CDR 2 and CDR 3. Conclusions: These results suggest that VD patients display more severe B-ADL difficulty, while AD patients display more severe memory difficulty and disorientation. B-ADL progresses in the earlier stages in VD and in Received January 22, 2006 Accepted April 24, 2006 *Kim Jae Woo, M.D. Department of Neurology, Dong-A University College of Medicine 1 Dongdaisindong 3-ga, Seo-gu, Busan, , Korea Tel: Fax: jwkim@mail.donga.ac.kr the later stages in AD. Global cognitive dysfunction progression is the opposite: in the earlier stages in AD and in the later stages in VD. J Korean Neurol Assoc 24(4): , 2006 Key Words: Alzheimer's disease, Vascular dementia, Comprehensive, Difference J Korean Neurol Assoc Volume 24 No. 4,

2 김태유김수영김응규김재우박경원성상민손태홍안경숙유봉구윤수진윤성민이상찬정해관최문성홍태용부산 경남치매학회 서론 치매의중요한원인인알츠하이머병과혈관성치매의임상양상차이를이해하는것은각질환에대한이해와치료방침의결정에중요하다. 이와같은중요성때문에, 두질환의임상양상차이를비교한연구가많았다. 1-3 그러나대부분진행정도를구분하지않고비교하여, 진행정도에따라차이가있는지를알수없었다. 그리고대상군이나연구방법에따라결과가달라, 여러증상을동시에조사비교한연구결과를고찰하는것이더타당하지만, 종합적으로고찰한연구는많지않다. 치매의진행과정도중요한임상적특성중하나인데, 서서히진행하는알츠하이머병과달리, 뇌혈관질환에의해갑자기나빠지는혈관성치매는진행과정이다를것으로예측되지만연구자마다결과가달랐다. 2-6 최근에는경도인지장애상태의혈관성치매와알츠하이머병환자의진행과정을비교할정도로연구가활발하지만, 7 국내에서는이에대한연구가없었다. 따라서저자들은치매환자에서나타나는주된증상인인지기능과비인지기능인일상생활능력, 행동심리적증상을전반적으로조사한후, 진행정도를구분하여차이를알아보고, 원인별진행과정의차이도알아보고자하였다. 선행연구에서자세한신경심리검사도구를사용한연구는많았지만, 임상에서흔히사용되는치매검사도구에대한비교는많지않아, 이들검사도구를사용하여다기관연구로알아보았다. 대상과방법 1. 대상 2004 년 3월부터 2004 년 5월까지지역사회에거주하면서, 부산, 경남지역의 9개의료센터에서 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders 4th edition) 8 진단기준에의해치매로진단된 150 명의환자를대상으로하였다. 모든환자에서뇌전산화단층촬영또는뇌자기공명영상검사를시행하였는데, 이를바탕으로 National Institute of Neurological and Communicative Disorders and Stroke-the Alzheimer's Disease and Related Disorders Association (NINCDS- ADRDA) 9 진단기준중 probable 에부합하는 93 명의알츠하이머병환자와 National Institute of Neurological Disorders and Stroke and the Association International pour la recherche et l'enseignement en Neurosciences (NINDS- AIREN) 10 진단기준의 probable 또는 possible 에부합하는 45명의혈관성치매환자를대상으로하였다. 적어도 3개월이 상치매환자와동거한가족중주부양자가원칙적으로응답하였는데, 본연구의취지에동의하여동의서에서명한 138 명을최종대상으로하였다. 2. 방법환자의나이, 학력, 성별등의인구사회학적특성을조사하였고, 전반적인치매상태평가를위해다음의검사도구를사용하였다. 치매선별검사는한국판간이정신상태검사 Korean version of Mini-Mental State Examination (K-MMSE), 11 전반적인치매진행정도를평가하기위해 Korean version of expanded Clinical Dementia Rating scale (CDR), 12 행동심리적증상평가를위해 Korean version of Neuropsychiatric Inventory (K-NPI), 13 육체적일상생활능력평가를위해 Barthel Index of Activity of Daily Living (B-ADL), 14 도구적일상생활능력평가를위해 Korean version of Instrumental Activity of Daily Living (K-IADL), 15 치매환자에게나타나는다양한인지기능장애를알아보기위해보호자가평가하는치매설문지를사용하였는데, 이는 Short form of Samsung Dementia Questionnaire (S-SDQ) 16 를사용하였다. 연구방법으로는알츠하이머병군과혈관성치매군으로나누어사회인구학적차이를비교하였다. K-MMSE, CDR, K-NPI, B-ADL, K-IADL, S-SDQ 점수와 CDR 과 K-MMSE 의세부영역점수의기술통계를구하였다. 그리고치매의진행정도에따른차이를알아보기위하여, 전체환자및 CDR 등급별로나누어두군간의차이를 t-test 로검증하였다. 이때, CDR 의진행정도에따라서발생할수있는환자의연령차이에의한효과를통제하기위하여공분산분석 (ANCOVA) 도동시에시행하였다. 그리고 CDR 등급별각검사도구의점수차이가있는지를 one way ANOVA test 로분석하였고, Tukey test 로사후분석하여진행과정에차이가있는지를분석하였다. 성비는 Chi square test 로검정하였다. 모든통계는 SPSS 10.0 version 통계프로그램을이용하였으며, p 값이 0.05 미만인경우를통계적으로의미있는결과로판단하였다. 결과 1. 인구사회학적특성 전체대상환자중여자는 85명 (61.6%), 남자는 53명 (38.4%) 이었으며, 평균연령은 72.9±8.4 세 (mean±sd), 평균학력은 2.4±1.3 단계, K-MMSE 는 16.6±6.3점, CDR 은 1.3±0.7, K- 338 J Korean Neurol Assoc Volume 24 No. 4, 2006

3 알츠하이머병과혈관성치매에서의진행정도에따른임상양상의차이 Table 1. Demographic characteristics of patients and the differences of mean scores of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K-NPI), Korean version of expanded Clinical Dementia Rating scale (CDR), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K-IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) Age Sex (M/F) Education n / e / m / h / c CDR 0.5/1/2/3 K-MMSE K-NPI Barthel Index Instrumental ADL S-SDQ CDR Sum of Box Total AD VD p value 72.9± / / 46 / 13 / 22 / / 66 / 34 / ± ± ± ± ± ± ± / / 31/ / 6 / 12 / / 46 / 26 / ± ± ± ± ± ± ± / 23 10/15/7/10/3 10 / 20 / 8/7 17.2± ± ± ± ± ± b a n; no education, e; elementary school, m; middle school, h; high school, c; college graduate or over, AD; Alzheimer's disease, VD; Vascular dementia. a p<0.05, b p<0.01. NPI 총점은 22.5±22.6 점, B-ADL 은 16.6±5.4 점, K-IADL 은 1.4±0.9점, S-SDQ 는 18.5±10.2점이었다 (Table 1). 알츠하이머병환자는 93명 (67.4%), 혈관성치매환자는 45명 (32.6%) 이었다. 혈관성치매군의평균연령은 69.4±9.4 세, 평균학력은 2.6±1.2 단계이었고, 알츠하이머병군의평균연령은 74.6± 7.4세, 평균학력은 2.3±1.4단계이었다 (Table 1). 알츠하이머병군과혈관성치매군의사회인구학적특성을비교해보면알츠하이머병군이나이가많고 (p<0.01), 성비와 (χ 2 =3.080, p= 0.079), 학력은차이가없었다 (Table 1). 2. 알츠하이머병과혈관성치매의임상적특성차이전체환자를대상으로한경우, B-ADL 이혈관성치매군에 서낮아육체적일상생활능력장애가심했지만, 다른검사도구에서는차이가없었다. CDR 등급별로나누어비교해보면, B- ADL 은 CDR 0.5 와 CDR 2 등급에서혈관성치매군에서장애가심했지만, CDR 1과 CDR 3에서는통계적차이가없었다. 그러나연령의영향력을통제한후에는 CDR 1에서도혈관성치매군에장애가심했다. K-MMSE 는다른등급에서는차이가없었지만, CDR 2에서알하이머병군에서점수가낮았다 (Table 1~5)(p<0.05). 그러나연령의영향력을통제한후에는차이가없었다 (F=3.175, p= 0.085)(Table 4). CDR 의세부영역인기억력, 지남력, 판단과문제해결능력, 사회활동, 집안생활과취미, 위생과몸치장의점수로원인별차이를조사한연구가있어, 17 같은방법으로조사하였는데, 전 Table 2. Demographic characteristics and the differences of mean scores of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K-NPI), Korean version of expanded Clinical Dementia Rating scale (CDR), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K-IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) in CDR 0.5 patients AD VD p F 1 (p) 2 Age Sex (M/F) Education n/e/m/h/c K-MMSE K-NPI Barthel Index Instrumental ADL S-SDQ CDR Sum of Box 74.9±9.3 6/9 4/6/1/3/1 21.7± ± ± ± ± ± ±5.7 4/6 2/4/3/1/0 20.3± ± ± ± ± ± a (0.439) (0.271) (0.025 a ) (0.258) (0.951) (0.438) n; no education, e; elementary school, m; middle school, h; high school, c; college graduate or over, Alzheimer's disease, VD; Vascular dementia. a p< ; F-value after controlling the effect of age derived from ANCOVA, 2; p-value after controlling the effect of age derived from ANCOVA. J Korean Neurol Assoc Volume 24 No. 4,

4 김태유김수영김응규김재우박경원성상민손태홍안경숙유봉구윤수진윤성민이상찬정해관최문성홍태용부산 경남치매학회 Table 3. Demographic characteristics and the differences of mean scores of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K-NPI), Korean version of expanded Clinical Dementia Rating scale (CDR), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K-IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) in CDR 1 patients Age Sex (M / F) Education n / e / m / h / c K-MMSE K-NPI Barthel Index Instrumental ADL S-SDQ CDR Sum of Box AD VD p F 1 (p) ±6.8 9/11 17/12/5/5/7 21.7± ± ± ± ± ± ± / 27 4/9/1/6/0 19.3± ± ± ± ± ± b (0.745) (0.303) (0.025 a ) (0.045 a ) (0.423) (0.717) n; no education, e; elementary school, m; middle school, h; high school, c; college graduate or over, Alzheimer's disease, VD; Vascular dementia. a p<0.05, b p< ; F-value after controlling the effect of age derived from ANCOVA, 2; p-value after controlling the effect of age derived from ANCOVA. Table 4. Demographic characteristics and the differences of mean scores of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K-NPI), Korean version of expanded Clinical Dementia Rating scale (CDR), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K-IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) in CDR 2 patients Age Sex (M / F) Education n / e / m / h / c K-MMSE K-NPI Barthel index Instrumental ADL S-SDQ CDR Sum of Box AD VD P F 1 (p) ±7.4 6/20 8/9/2/2/5 12.6± ± ± ± ± ± ±14.6 4/4 1/2/2/0/3 17.5± ± ± ± ± ± a a b (0.085) (0.572) (0.002 b ) (0.392) (0.452) (0.238) n; no education, e; elementary school, m; middle school, h; high school, c; college graduate or over, Alzheimer's disease, VD; Vascular dementia. a p<0.05, b p< ; F-value after controlling the effect of age derived from ANCOVA, 2; p-value after controlling the effect of age derived from ANCOVA. Table 5. Demographic characteristics and the differences of mean scores of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K-NPI), Korean version of expanded Clinical Dementia Rating scale (CDR), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K-IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) in CDR 3 patients Age Sex (M/F) Education n/e/m/h/c K-MMSE K-NPI Barthel Index Instrumental ADL S-SDQ CDR Sum of Box AD VD P F 1 (p) ±6.8 1/6 3/0/1/3/0 6.6± ± ± ± ± ± ±5.3 4/2 3/3/0/0/0 4.7± ± ± ± ± ± (0.229) (0.913) (0.149) (0.652) (0.128) (0.922) n; no education, e; elementary school, m; middle school, h; high school, c; college graduate or over, Alzheimer's disease, VD; Vascular dementia. 1; F-value after controlling the effect of age derived from ANCOVA, 2; p-value after controlling the effect of age derived from ANCOVA. 340 J Korean Neurol Assoc Volume 24 No. 4, 2006

5 알츠하이머병과혈관성치매에서의진행정도에따른임상양상의차이 Figure 1. Mean subscale's scores of Korean version of expanded Clinical Dementia Rating scale (CDR) stratified by CDR level in Alzheimer's disease (AD) and vascular dementia (VD). M; memory, O; orientation, JP; judgment and problem solving, CA; community affairs, HH; home and hobbies, PC; personal care. a Significantly different from VD group (p<0.05). 체환자를대상으로한경우모든영역에서통계적차이가없었다 (p=0.133~0.790). 그러나 CDR 등급별로나누어연령의영향력을통제한후비교해보면일부차이가있었는데, CDR 0.5 에서 CDR 의기억영역이알츠하이머병군에서장애가심했다 (F=4.314, p=0.050). 그리고 CDR 2에서기억영역과 (F=6.581, p=0.015) 지남력영역이알츠하이머병군에서장애가심했다 (F=13.116, p=0.001)(fig. 1). CDR 3인혈관성치매군에서기억력, 지남력, 판단과문제해결능력의평균점수는 2.6 점이하, CDR 2인혈관성치매군에서는 1.5 점이하로낮아, 이들영역에서혈관성치매환자군의장애가치매등급에비해경한양상을보였다. 자세한인지기능평가는될수없지만, K-MMSE 의시간지남력, 장소지남력, 기억등록, 주의집중및계산, 기억회상, 언어및시공간구성능력점수를세부적으로나누어차이를알아보았다. 전체환자를대상으로한경우, 장소지남력이알츠하이머병군에서점수가낮았고 (p<0.05), 다른영역은차이가없었다. CDR 등급별로나누어연령의영향력을통제한후비교해보면, CDR 1에서장소지남력이알츠하이머병군에서점수 가낮았고 (F=4.818, p=0.032), CDR 2에서는알츠하이머병군의장소지남력과 (F=6.155, p=0.019)(p<0.05) 기억회상 (F= 4.410, p=0.047) 점수가낮았다. 그러나다른등급이나영역에서는차이가없었다. 3. 알츠하이머병과혈관성치매의진행과정의차이종적연구가아니기때문에진행과정의차이를정확히알수는없으나, CDR 등급에따른각점수의변화로진행과정의차이를간접적으로살펴보았다. 알츠하이머병군은모든검사도구에서 CDR 등급에따른차이가있었는데 (F=4.501~26.557, p<0.01), 사후분석에서 K-MMSE 는 CDR 0.5 와 CDR 1에서 3.5 점으로유의한차이가없었지만 (p=0.077), CDR 1과 CDR 2 에서 5.6 점, CDR 2와 CDR 3에서 6점으로차이를보였다 (p<0.01). K-NPI 는 CDR 0.5와 CDR 1에서 1.9점 (p=0.993), CDR 2와 CDR 3에서 15.2 점으로차이가없었지만 (p=0.496), CDR 1과 CDR 2에서는 20점으로차이를보였다 (p<0.01). B-ADL 은 CDR 0.5 와 CDR 1에서 1점으로차이가없었지만 J Korean Neurol Assoc Volume 24 No. 4,

6 김태유김수영김응규김재우박경원성상민손태홍안경숙유봉구윤수진윤성민이상찬정해관최문성홍태용부산 경남치매학회 (p=0.8168), CDR 1과 CDR 2에서 2.6점, CDR 2와 CDR 3에서 6.7 점으로차이를보였다 (p<0.01). K-IADL은 CDR 0.5와 CDR 1에서는 0.5 점으로차이가없었지만 (p=0.160), CDR 1과 CDR 2 (p<0.01) 에서 0.8점, CDR 2와 CDR 3에서 0.9점으로차이를보였다 (p<0.05). S-SDQ는 CDR 1과 CDR 2에서 4점 (p=0.409), CDR 2와 CDR 3에서 7.5 점으로차이가없었지만 (p=0.498), CDR 0.5 와 CDR 1에서는 8.2 점으로차이가있었다 (p<0.05). CDR Sum of Box 는 CDR 0.5와 CDR 1에서 2.3 점 (p=0.934), CDR 2와 CDR 3에서 7.1 점으로차이가없었지만 (p=0.140), CDR 1과 CDR 2에서는 4.4 점으로차이를보였다 (p<0.05)(fig. 2, 3). 혈관성치매군도모든검사도구에서 CDR 등급에따른차이가있었는데 (F=4.916~20.540, p<0.01), 사후분석에서 K- MMSE는 CDR 0.5와 CDR 1에서 1.0점 (p=0.931), CDR 1과 CDR 2에서 1.8 점으로차이가없었지만 (p=0.701), CDR 2와 CDR 3에서는 12.8 점으로차이를보였다 (p<0.01). K-NPI 는 CDR 0.5와 CDR 1에서 9.4점 (p=0.337), CDR 2과 CDR 3에서 12.5 점으로차이가없었지만 (p=0.345), CDR 1와 CDR 2에서는 16.4 점으로차이를보였다 (p<0.05). B-ADL 은 CDR 0.5와 CDR 1에서 1.2점 (p=0.934), CDR 2와 CDR 3에서 6.3점으로 차이가없었지만 (p=0.140), CDR 1과 CDR 2에서는 7점으로차이를보였다 (p<0.05). K-IADL 은 CDR 0.5와 CDR 1에서 0.4 점 (p=0.219), CDR 2와 CDR 3 에서 0.7 점으로차이가없었지만 (p=0.090), CDR 1과 CDR 2에서는 0.9 점으로차이를보였다 (p<0.01). S-SDQ는 CDR 1과 CDR 2에서 4.3점 (p=0.362), CDR 2와 CDR 3에서 4.8 점으로차이가없었지만 (p=0.462), CDR 0.5와 CDR 1에서는 6.5 점으로차이가있었다 (p<0.05). CDR Sum of Box는 CDR 0.5 와 CDR 1에서 2.3 점 (p=0.934), CDR 2와 CDR Figure 2. The changes of Korean version of Mini-Mental State Examination (K-MMSE), Korean-Neuropsychiatric Inventory (K- NPI), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K- IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) with progression in Alzheimer's disease (AD) and vascular dementia (VD). *Significantly different from VD group (p<0.05). Figure 3. The difference of Korean version of Mini-Mental State Examination (K-MMSE), Korean- Neuropsychiatric Inventory (K-NPI), Barthel Index of Activity of Daily Living (B-ADL), Korean version of Instrumental Activity of Daily Living (K- IADL), Short form of Samsung Dementia Questionnaire (S-SDQ) scores between Korean version of expanded Clinical Dementia Rating scale (CDR) grades in Alzheimer's disease (AD) and vascular dementia (VD). 342 J Korean Neurol Assoc Volume 24 No. 4, 2006

7 알츠하이머병과혈관성치매에서의진행정도에따른임상양상의차이 3에서 7.1 점으로차이가없었지만 (p=0.140), CDR 1과 CDR 2 에서는 4.4점 (p<0.05) 으로차이를보였다 (Fig. 2, 3). 고찰 1. 알츠하이머병과혈관성치매의임상적특성차이 국내에서도두질환의신경심리적차이를비교한연구가있었는데, 18,19 혈관성치매의경우전두엽성기능장애를주로보이고, 알츠하이머병은기억장애가주가되는것으로잘알려져있다. 1 본연구에서전체환자를대상으로한경우육체적일상생활능력장애가혈관성치매군에서심해다른연구와 18,20 일치하였다. 그러나다른검사도구에서는원인별차이가없었다. 알츠하이머병군에서비교적심한육체적일상생활능력장애가중증에서나타났지만, 혈관성치매군은초기부터나타났다. 이것은혈관성치매에동반된신경학적증상때문으로생각된다. 행동심리적증상을평가하는 K-NPI 는여러증상의합으로점수가산출되는데, 총점에서는두군간에큰차이가없었다. 그러나개별증상에서는차이가있는것으로보고되었다. 21,22 본연구는치매의진행정도를구분하여비교했기때문에, 원인별임상양상의차이를보다자세히알수있었는데, K- MMSE 점수와육체적일상생활능력에서 CDR 등급별로나눈경우전체환자를대상으로한경우와차이가있어, 진행정도를구분하여조사하는것이타당함을알수있었다. 알츠하이머병과혈관성치매의진행정도를구분하여비교한 Bowler 등 3 의연구에의하면, 초기에는알츠하이머병의기억장애가더심한것으로보고되었는데, 본연구에서도 CDR 0.5 에서 CDR 의기억영역점수가알츠하이머병군에서높아같은결과를보였다. 그리고 CDR 1에서 K-MMSE 의장소지남력과 CDR 2에서 CDR 의기억영역, 지남력, 그리고 K-MMSE 의장소지남력, 기억회상영역의장애가알츠하이머병군에서심했다. 국내에서알츠하이머병과혈관성치매의비교연구는있었지만, MMSE 과 CDR 의세부영역별점수를구분하여조사한연구는없었는데, 본연구결과이들영역별점수에서도차이가있었다. 앞서의결과를종합해보면혈관성치매군은전반적으로육체적일상생활능력장애가심하고, 알츠하이머병군은기억장애와지남력장애가초기부터중등도까지더심한특성이있었다. 이러한임상양상의원인으로는여러가지기전들이언급되고있는데, 피질하허혈성혈관치매의경우, 주로피질과피질하뇌영역간의단절에의한것으로알려져있었다. 23 그러나 최근에는허혈에민감한해마와전두정엽피질의허혈손상이나, 24 피질하뇌경색에의한전반적인뇌대사저하, 25 그리고뇌관류및대뇌피질과해마의부피감소 26 등이원인으로언급되고있다. 치매의특징적인증상중하나인행동심리적증상도대뇌피질손상이원인으로보고되었다. 27 최근에는혈관성요소가알츠하이머병의위험요소로도알려져있는데, 28,29 알츠하이머병은후방뇌관류장애, 혈관성치매는전방부뇌관류장애가주로나타나기때문에, 임상양상차이가나는것으로보고되었다 알츠하이머병과혈관성치매의진행과정차이혈관성치매는이질적인특성을가진질환군으로, 갑자기발병하면서계단식진행을가지는것으로알려져있다. 그러나피질하허혈성혈관치매 (subcortical ischemic vascular dementia; SIVD) 의경우는 lacunar state 와 Binswanger's disease 를포함하는비교적동질성을가진질환군으로 31,32 서서히악화되는알츠하이머병과비슷한진행과정을가지는것으로도보고되었다. 7 종적연구결과인지기능의진행속도가알츠하이머병과비슷하다는보고가있었지만, 5,6 혈관성치매에서느리다는보고도있어, 2 연구자마다차이가있다. 본연구는종적연구가아니기때문에진행과정을단정하기는어렵지만, 국내에서혈관성치매의진행과정에대한연구가거의없었기때문에, 대략의진행과정을가늠해보는데, 의의가있다고생각된다. CDR 등급에따른점수변화로미루어보면, 초기에는혈관성치매의진행속도가비슷하거나약간느렸고, 중등도부터는빨리진행하여, 진행정도에따라차이가있는것으로생각된다. 혈관성치매의경우 1년에 MMSE 점수가 1.75 점 33 ~4-5 점 5 까지감소하는것으로보고되어연구자마다차이가있었다. 특히혈관성치매의경우추가적인뇌경색발생이진행과정의중요한요소가되는데, 34 이를구분한연구에의하면열공경색혈관치매에서추가적인뇌경색이없는경우 MMSE 점수가 0.95 점 /year, 추가적인뇌경색이있는경우 2.09 점 /year, 두군을합한경우 1.44 점 /year 으로차이가있었다. 34 혈관성치매의진행은새로운뇌졸중의발생뿐아니라, 만성적인뇌관류장애도주된원인으로주장되었다. 23 행동심리적증상도열공경색증성혈관치매에서추가적인뇌경색이없는경우, NPI 점수가 2.0 점 /year, 추가적인뇌경색이있는경우 11.3 점 /year 이증가하는것으로보고되었는데, 34 본연구에서혈관성치매군은 CDR 0.5 에서 CDR 1로진행할때 NPI 점수 9.4 점이급격히증가하였고, 알츠하이머병군은 CDR 1에서 CDR 2로진행할때 20 점이급격히증가해, 행동심리적증상이혈관성치매에서는초기에악화되는것으로 J Korean Neurol Assoc Volume 24 No. 4,

8 김태유김수영김응규김재우박경원성상민손태홍안경숙유봉구윤수진윤성민이상찬정해관최문성홍태용부산 경남치매학회 생각된다. 알츠하이머병의경우행동심리적증상이인지장애와비례하여계속나빠지거나, 중등도에서심해지고이후에호전을보인다는상반된보고가있는데, 35 본연구에서는 CDR 2에서 K-NPI 총점이제일높고, CDR 3에서는감소하여후자에부합하였다. 혈관성치매군도 CDR 2에서총점이제일높고 CDR 3에서감소하였는데, 이것은심등 36 의연구결과와같았다. 알츠하이머병군과혈관성치매군모두 S-SDQ 를제외한검사에서, CDR 0.5 와 CDR 1로진행할때는변화정도가크지않다가, CDR 1부터진행정도가심해지는양상을보였다. 그리고알츠하이머병군의경우사용된검사도구모두, CDR 0.5 에서 CDR 3까지진행하는과정에서모든등급간에차이를보였다. 혈관성치매군도같은경향을보였지만, CDR 2에서 CDR 3으로진행하면서악화는되었지만통계적차이가없었다. 이것은혈관성치매군의수가적어서나타난것으로추측되며, 보다많은환자를대상으로한다면통계적으로차이가있을것으로생각된다. 그리고 S-SDQ 가 CDR 0.5 와 CDR 1 사이에서만차이를보인것은초기변화에민감한특성을가지기때문으로생각된다. 초기에알츠하이머병군의기억장애가심했지만, 중등도부터혈관성치매군의진행속도가빨라져, 중증에서는알츠하이머병군의기억장애정도와비슷해졌는데, 이는 Bowler 등 3 과같은결과였다. 혈관성치매군의육체적일상생활능력은 CDR 1에서 CDR 2로진행하면서급격히악화되었지만, 알츠하이머병군은 CDR 2에서 CDR 3으로진행할때급격히악화되어차이를보였다. 알츠하이머병군은 CDR 0.5 부터 K-MMSE 점수가지속적으로악화되는경향을보였지만, 혈관성치매군은 CDR 2까지는큰변화가없다가, CDR 3에서급격히감소해진행양상이달랐다. 이것은혈관성치매가전두엽성기능장애를주로나타내지만, MMSE 는전두엽기능변화에민감하지못해 37 CDR 1에서 CDR 2로진행하는과정에서전두엽성기능장애를반영하지못하다가, CDR 3으로진행하면서전두엽성기능장애가, 역치를넘어다른영역의인지기능까지영향을미쳤기때문에, 갑자기점수가떨어진것으로추측해볼수있겠다. 이것은 Fig. 1에서보는바와같이 CDR 2인혈관성치매군의 CDR 세부영역중기억력, 지남력, 판단능력의점수가 0.8 과 1.5 정도로치매의전반적인정도에비해장애가경하다가, CDR 3에서 2.6 으로갑자기심해진것과 CDR 2인혈관성치매군의 K- MMSE 의장소지남력, 기억회상영역의점수가같은등급의알츠하이머병군보다높았던것으로미루어유추해볼수있겠다. 하지만대상군수가 8명으로적었기때문에많은대상자를상대로보다자세한연구가필요하겠다. 알츠하이머병과병리기전은다르지만, 혈관성치매도서서 히진행한다는연구결과가있었는데, 7 본연구에서도일부차이는있었지만, 서서히진행하면서, 전반적인영역에서비슷한정도의장애를보였다. 이것은혈관성치매가국소적인증상의발현보다는알츠하이머병과같이전반적인뇌기능장애를보였기때문으로생각된다. 이러한현상은본연구의혈관성치매군에피질하허혈성혈관치매환자가많이포함되었거나, 피질하뇌경색이전반적인뇌대사장애를 25 일으켰기때문으로생각된다. 만약전략적뇌경색치매환자를대상으로했다면, 특정영역의장애가심했을수도있지만이에대하여는보다자세한연구가필요할것이다. 기존의혈관성치매에대한연구에서제기되었던문제점은, 첫째혈관성치매가동질성을가지는질환군이어서알츠하이머병과비교가가능한지가불확실한것이고, 둘째대상군에순수한알츠하이머병과혈관성치매환자이외의치매환자가포함되었을가능성이높고, 셋째아형을정확히분류하지못한경우가많았다는것이다. 본연구도앞서의문제점을극복하지못한제한점이있다. 그리고증상이심한입원환자가제외된외래환자를대상으로하여, 중증환자의차이는알수가없었고, 약물치료를하고있어증상이경했을수도있다. 그리고 CDR 등급별환자수가적었고, 사회인구학적차이가있었으며, 단면적연구였기때문에제한점은있으나, 전반적인차이를이해하는데는도움이되리라생각한다. 따라서보다정확한결과를얻기위해서는적절하게통제된많은환자를대상으로하는추적연구가필요할것이다. 임상적으로알츠하이머병을진단받은환자의병리적연구에의하면, 이들환자의뇌조직에서뇌병변이나아밀로이드뇌혈관병증 (cerebral amyloid angiopathy) 의발현률이 57.3% 와 33.2% 로대조군에비해절대적으로나상대적으로높고, 38 순수한알츠하이머병은 25% 정도로낮게보고되었다. 39 이것은노인에있어알츠하이머병과뇌혈관질환의유병률이모두높기때문으로, 노인치매환자들은두질환을동시에가질가능성이높다. 따라서혼합성치매의유병률이높을가능성이많기때문에, 앞으로는이에대한연구도필요하다. 그리고아형별유병률도중요하기때문에이에대한연구도필요할것으로생각된다. 결론적으로알츠하이머병에서초기에기억장애와, 지남력장애가더심하였고, 혈관성치매는전반적으로육체적일상생활능력장애가심했다. 혈관성치매는중등도이상에서인지기능의악화속도가빨라지는경향을보였다. 혈관성치매의육체적일상생활능력은경증에서중등도로진행하면서급격히악화되었으나, 알츠하이머병은중등도에서중증으로진행할때급격히악화되었다. 344 J Korean Neurol Assoc Volume 24 No. 4, 2006

9 알츠하이머병과혈관성치매에서의진행정도에따른임상양상의차이 REFERENCES 1. Kertesz A, Clydesdale S. Neuropsychological deficits in vascular dementia vs Alzheimer s disease. Frontal lobe deficits prominent in vascular dementia. Arch Neurol 1994;51: Nyenhuis DL, Gorelick PB, Freels S, Garron DC. Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia. Neurology 2002;8:58: Bowler JV, Eliasziw M, Steenhuis R, Munoz DG, Fry R, Merskey H, et al. Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia. Arch Neurol 1997;54: Laukka EJ, Jones S, Small BJ, Fratiglioni L, Backman L. Similar patterns of cognitive deficits in the preclinical phases of vascular dementia and Alzheimer s disease. J Int Neuropsychol Soc 2004;10: Ballard C, O'Brien J, Morris CM, Barber R, Swann A, Neill D, et al. The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer s disease. Int J Geriatr Psychiatry 2001;16: Ballard C, Patel A, Oyebode F, Wilcock G. Cognitive decline in patients with Alzheimer s disease, vascular dementia and senile dementia of Lewy body type. Age Ageing 1996;25: Meyer JS, Xu G, Thornby J, Chowdhury MH, Quach M. Is mild cognitive impairment prodromal for vascular dementia like Alzheimer s disease? Stroke 2002;33: American Psychiatric Association Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4th ed. Washington DC: American Psychiatric Association, McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer s disease report of the NINCDS-ADRDA Work Group Under the auspices of Department of Health and Human Services Task Force On Alzheimer's Disease. Neurology 1984;34: 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: Kang YW, Na DL, Hahn S. A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J Korean Neurol Assoc 1997;15: Choi SH, Na DL, Lee BH, Hahnm DS, Jeong JH, Yoon SJ, et al. Estimating the validity of the Korean version of expandedclinical Dementia Rating Scale (CDR). J Korean Neurol Assoc 2001;19: Choi SH, Na DL, Kwon HM, Yoon SJ, Jeong JH, Ha CK. The Korean version of the neuropsychiatric inventory: a scoring tool for neuropsychiatric disturbance in dementia patients. J Korean med Sci 2000;15: Mahoney FI, Barthel DW. Functional evaluation; The Barthel index. Md state Med J 1965;14: Kang SJ, Choi SH, Lee BH, Kwon JC, Na DL, Han SH, Korean dementia group. The reliability and validity of the Korean instrumental activity of daily living (K-IADL). J Korean Neurol Assoc 1999;17: Choi SH, Na DL, Oh KM, Park BJ. A Short form of the Samsung Dementia Questionnaire (S-SDQ): development and cross-validation. J Korean Neurol Assoc 1999;17: Rosen HJ, Narvaez JM, Hallam B, Kramer JH, Wyss-Coray C, Gearhart R, et al. Neuropsychological and functional measures of severity in Alzheimer disease, frontotemporal dementia, and semantic dementia. Alzheimer Dis Assoc Disord 2004;18: Park KW, Park MJ, Cheon SM, Kim JK, Cha JK, Kim SH, et al. Neurospychological difference between subcortical vascular dementia and Alzheimer disease. J Korean Neurol Assoc 2005;23: Kim DS, Hahm DS, Kwak YT, Han IW. Neuropsychological difference between Alzheimer disease and vascular dementia. J Korean Neurol Assoc 2001;19: Kim JM, Lyons D, Shin IS, Yoon JS. Differences in the behavioral and psychological symptoms between Alzheimer s disease and vascular dementia: are the different pharmacologic treatment strategies justifiable? Hum Psychopharmacol 2003;18: Kim TY, Kim SY, Kim JW, Park KW, Yoo BG, Lee SC. The change of behavioral and psychological symptoms according to the progression of Alzheimer s disease. J Korean Neurol Assoc 2004;22: Chiu E. Vascular burden and BPSD: a reconceptualization. Int Psycholgeriatr 2003;15 Suppl 1: Cohen RA, Paul RH, Zawacki TM, Sethi M, Ott BR, Moser DJ, et al. Single photon emission computed tomography, magnetic resonance imaging hyperintensity, and cognitive impairments in patients with vascular dementia. J Neuroimaging 2001;11: Farkas E, de Wilde MC, Kiliaan AJ, Luiten PG. Chronic cerebral hypoperfusion-related neuropathologic changes and compromised cognitive status: window of treatment. Drugs Today 2002;38: Kwan LT, Reed BR, Eberling JL, Schuff N, Tanabe J, Norman D, et al. Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function. Arch Neurol 1999;56: Fein G, Di Sclafani V, Tanabe J, Cardenas V, Weiner MW, Jagust WJ, et al. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology 2000; 12:55: Fuh JL, Wang SJ, Cummings JL. Neuropsychiatric profiles in patients with Alzheimer s disease and vascular dementia. J Neurol Neurosurg Psychiatry 2005;76: Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke 2004;35 Suppl 1: Bidzan L, Bidzan M. Vascular factors and progression of cognitive decline in elderly people. Psychiatr Pol 2005;39: Yoshikawa T, Murase K, Oku N, Imaizumi M, Takasawa M, Rishu P, et al. Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia. Am J Neuroradiol 2003;24: Erkinjuntti T. Subcortical vascular dementia. Cerebrovasc Dis 2002; 13 Suppl 2: Shim YS, Yang DW, Kim BS, Shon YM, Lee DG, Chung YA, et al. Analysis of SPECT in two sub-type of subcortical ischemic vascular dementia. J Korean Neurol Assoc 2005;23: Small BJ, Backman L. Predictors of longitudinal changes in memory, visuospatial, and verbal functioning in very old demented adults. Dement Geriatr Cogn Disord 1998;9: J Korean Neurol Assoc Volume 24 No. 4,

10 김태유김수영김응규김재우박경원성상민손태홍안경숙유봉구윤수진윤성민이상찬정해관최문성홍태용부산 경남치매학회 34. Aharon-Peretz J, Daskovski E, Mashiach T, Kliot D, Tomer R. Progression of dementia associated with lacunar infarctions. Dement Geriatr Cogn Disord 2003;16: Kim TY, Kim SM, Choi SH, Yoo BG, Lee SC, Park KW, et al. A 1-year follow-up study of behavioral and psychological symptoms in patients with Alzheimer s disease. J Korean Geriatr Soc 2004; 8: Shim YS, Kim BS, Shon YM, Kim KS, Yoon BR, Yang DW. Clinical characteristics of demented patients in a geriatric institution: focused Behavioral and psychological symptoms. J Korean Neurol Assoc 2005;4: Gauthier S. Clinical diagnosis and management of Alzheimer s disease. 1st. ed. London: Martin dunits, 1996; Jellinger KA, Attems J. Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease. J Neurol Sci 2005;15: Fernando MS, Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004: 15:226: J Korean Neurol Assoc Volume 24 No. 4, 2006