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1 원저 J Korean Neurol Assoc / Volume 23 / June, 2005 서울대학교의과대학신경과학교실, 대전을지대학병원신경과 a 임준성김정은 a 백민재박성호김상윤 Subtypes and Their Clinical Characteristics of Mild Cognitive Impairment (MCI): Cross Sectional Study Jun-Seong Lim, M.D., Jung Eun Kim, M.D. a, MinJae Baek, M.S., Seong-Ho Park, M.D., SangYun Kim, M.D. Department of Neurology, Seoul National University College of Medicine, Seoul; Department of Neurology, Dae-jeon Eulji University Hospital a, Daejeon, Korea Background: Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia. Recently, the published MCI classification in The Current Concepts in MCI Conference suggested subtypes of MCI (amnestic, single nonmemory domain, multiple domains slightly impared) based on recognized heterogeneity. The purpose of this study was to ascertain the existence of subtypes of MCI and investigate their relative prevalence and clinical characteristics. Methods: We recruited the MCI patients according to the consensus criteria of MCI. We classified them into 3 subtypes of MCI by our working criteria based on the definitions of MCI subtypes and then calculated their respective prevalence. We described their various clinical variables including demographic features, symptoms on the first visit, neuroimaging findings, and the genotype of apolipoprotein E. Results: Sixty patients (36 females and 24 males) were enrolled as MCI and analyzed. The prevalence of each subtype (amnestic, single nonmemory domain, multiple domains slightly impared) were 13 (21.67%), 24 (40.0%), and 23 (38.33%) respectively, suggesting the most prevalent type was the single nonmemory domain type. MCI cases with subcortical vascular features were 18 (11 single nonmemory domain and 7 multiple domains slightly impaired). The ApoE ε4 carriers were about 50% of tested patients. Conclusions: We ascertained the existence of MCI subtypes and investigated their prevalence and various clinical features. In evaluation of MCI patients, we should keep the notion of heterogeneity and subclassification in mind. Key Word: MCI, Subtypes, Heterogeneity J Korean Neurol Assoc 23(3): , 2005 Key Words: MCI, Subtypes, Heterogeneity 서론 알쯔하이머병, 전두측두엽치매, 그리고루이체치매등은병 Received November 1, 2004 Accepted December 10, 2004 *SangYun Kim, M.D., Ph.D. Clinical Neuroscience Center, Seoul National University Bundang Hospital 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, , Korea Tel: Fax: neuroksy@snu.ac.kr 이진행함에따라여러인지기능영역의심한감퇴와그로인한일상생활의장애를보이게되는데, 이들질환은모두뚜렷하지않은기억력및집중력의감소나성격과감정조절의미세한변화등을보이는치매의전단계를가지는것으로알려져있으며이를경도인지장애 (mild cognitive impairment; MCI) 라한다. 1 또한피질하뇌혈관질환에의한치매도증상발현이전의전단계, 즉혈관성경도인지장애를거쳐혈관성치매로발현된다. 분자생물학의급속한발달에따라인지기능의저하를억제하고퇴행성뇌질환의진행을지연또는완화하는약물들이개발되고있는현시점에치매를일으키는여러질환들을치매전 348 J Korean Neurol Assoc Volume 23 No. 3, 2005

2 단계에서조기에발견하여치료하면병의진행속도를늦출수있다는점에서이에대한관심이증폭되고있다. 2,3 처음에는경도인지장애의공통적인근본기준이제시되었고, 그후에주로알쯔하이머병의치매전단계의개념으로서 amnestic MCI criteria 가제안되었으며이를만족하는군을대상으로한연구에서알쯔하이머병으로의진행위험이높은군임이입증되었다. 하지만일부에서는인지기능이그대로유지되거나오히려호전되는경우도있어경도인지장애가균일한집단이아니라는생각을하게되었고, 최근에는경도인지장애를세가지유형으로나누어이에대한기준을제시하기에이르렀다. 4 저자들은그동안제시된경도인지장애판단기준들을바탕으로실제임상적용기준 (working criteria) 을결정하였고, 이기준에적합한군을선정하여경도인지장애의각유형의비율및뇌영상소견을포함한임상양상분석을통해경도인지장애의다양성또는이질성을알아보았다. 대상과방법 1. 대상 2003 년 5월부터 2004 년 5월까지분당서울대학교병원기억장애및뇌노화클리닉에내원한환자들중본인자신이기억력저하를직접의사에게호소하거나, 환자는호소하지않으나동 Table 1. Inclusion criteria of mild cognitive impairment 1 subjective memory complaint by the patient and/or the caregiver 2 K-MMSE mean-2 SD (for age and educational level) 3 CDR 0.5 and GDS 2 or 3 4 Barthel index = 20/20, K-IADL< no specific intracranial or systemic disease which can cause delirium or dementia 6 no recent history of regular medication which can affect cognitive function K-MMSE; Korean version of mini-mental state examination, CDR; clinical dementia rating scale, GDS; global deterioration scale, K-IADL; Korean version of instrumental activities of daily living, SD; standard deviation 거인이나일주일에 2회이상환자와만나는보호자가환자의기억력저하를보고하는경우, 또는환자와동거인및보호자모두가기억력저하를호소하는환자들을대상으로하였다, 한국형간이정신상태검사 (Korean version of mini-mental state examination; K-MMSE) 를하여총점이연령과교육수준을보정한평균값에서표준편차의 2배수를뺀값 ( 평균- 표준편차 2) 이상인환자들중, CDR (Clinical Dementia Rating Scale) 이 0.5이면서 GDS (Global Deterioration Scale) 가 2 또는 3으로일상생활에서는아무장애없이정상적인생활이가능한환자들을선택했다. 섬망을보이거나치매를유발할수있 Table 2. The definitions and working criteria of subtypes of mild cognitive impairment Subtypes Definitions Working criteria Amnestic MCI Single nonmemory domain MCI Multiple domains slightly impaired MCI subjective memory complaint normal general cognition / High MMSE isolated impairment in episodic memory subjective memory complaint normal general cognition / High MMSE isolated impairment in either visuospatial or language domain subjective memory complaint normal general cognition / High MMSE isolated impairment on 2+ tasks 1. subjective memory complaint 2. K-MMSE mean-2sd (for age & educational level) 3. CDR 0.5 and GDS 2 or 3 4. episodic memory score < 16% (-1SD) 5. Barthel index=20/20, K-IADL < subjective memory complaint 2. K-MMSE mean-2sd (for age & educational level) 3. CDR 0.5 and GDS 2 or 3 4. visuospatial score or language score or frontal function score < 16% (-1SD) 5. Barthel index = 20/20, K-IADL < subjective memory complaint 2. K-MMSE mean-2sd (for age and educational level) 3. CDR 0.5 and GDS 2 or or more area score < 16% (-1SD) 5. Barthel index = 20/20, K-IADL < 0.43 MMSE; mini-mental state examination, CDR; clinical dementia rating scale, GDS; global deterioration scale, K-IADL; Korean version of instrumental activities of daily living, SD; standard deviation, K-MMSE; Korean version of mini-mental state examination, MCI; mild cognitive impairment J Korean Neurol Assoc Volume 23 No. 3,

3 임준성김정은백민재박성호김상윤 Table 3. Neuropsychological tests for the evaluation of specific cognitive domains MCI 로분류하였다. Cognitive domain Neuropsychological tests 3. 검사및분석 Memory domain Language domain Fontal function domain Visuospatial function domain K-HVLT (verbal memory), Rey-figure test (visual memory) K-BNT Semantic or phonemic word fluency, Contrasting program, Go No-Go test, Stroop test Rey-figure test (copy) K-HVLT; Korean version of Hopkins verbal learning test, K-BNT; Korean version of Boston naming test 는다른두개내질환이나전신질환을갖는환자는대상에서제외하였고규칙적으로인지기능에영향을줄수있는약물을복용하는경우도제외하였다 (Table 1). 2. 경도인지장애아형에따른분류 최근제시된경도인지장애의세가지아형에대한정의에맞게환자들을분류하기위해연령과학력을고려한활용기준 (working criteria) 을마련하였고 (Table 2), 기준에명시된각인지영역을나타내는신경심리검사도구는자료조사를통해설정하였다 (Table 3). 4 이들을대상으로숙련된한명의신경심리사가전반적인신경심리검사를하였고, 이를바탕으로각아형으로나누었는데기억회상영역에서현저한저하를보이지만다른인지영역에서는비교적정상이거나혹은경미한저하만를보이는환자군을선정하여이를 amnestic MCI 로분류하였고, 기억회상영역이정상이면서언어영역, 전두엽기능영역, 또는시공간지각영역중한영역의현저한저하를보이는경우를 single nonmemory domain MCI, 그리고기억영역, 언어영역, 전두엽기능영역및시공간지각영역중 2개이상의영역에저하가있는경우를 multiple domains slightly impaired 이들에대한임상적특징을알아보기위해인구통계학적인특성 ( 연령, 성별, 교육연수 ), 호소하는증상및신경학적이상소견을검토하였고, 노인우울척도 (geriatric depression scale) 를조사하여 24점이상인경우는우울증이동반되어있는것으로판단하였다. 뇌 MRI 에서피질하혈관성변화를시사하는백질변성및열공경색소견의존재를육안으로관찰하였다. 4. 통계분석통계분석은 SPSS 10.0 (SPSS Inc. USA) 을사용하였다. 경도인지장애각아형간에나이, 교육연수및 K-MMSE 점수를일원분산분석으로비교하였고, 성별, 뇌 MRI 상백질변성및열공경색존재및우울증여부를교차분석을통해 pearson 카이제곱과점근유의확률을구하였다. 'single nonmemory domain MCI' 에서저하된인지영역의빈도를보기위해단일표본카이제곱검정을하였다. 모든기술통계량은평균과표준편차로나타내었고, 유의수준은 p<0.05 로하였다. 결과 1. 인구통계학적인분석 저자들이마련한경도인지장애기준에적합한환자는모두 60 명이었다. 이들에대한인구통계학적자료는 Table 4와같다. 각아형간의평균연령, 성비, 교육연수는통계학적으로유의한차이가없었다. 2. 내원시의주관적증상공통적인내원시증상은기억력의저하였는데이들대부분 Table 4. Demographic features of the subjects Amnestic MCI Single nonmemory domain MCI Multiple domains slightly impaired MCI p Age (year) Sex (male/female) Education (year) 63.8±10.6 5/8 14.2± ±7.6 9/ ± ±9.1 8/ ±4.3 NS <0.001 NS Data are mean±sd. Statistical significance was tested by Pearson's Chi square test and Student's t-test. MCI; mild cognitive impairment, NS; not significant 350 J Korean Neurol Assoc Volume 23 No. 3, 2005

4 은비교적서서히시작되었고증상의시작이언제인지뚜렷하지않았다. 가족이나친척중에치매증상을보인경우가있다고말한경우는 12명 (20%) 이었다. 기억력저하의사례중흔히보이는것은최근에들은대화내용을잊어버리거나같은말을반복하는등의언어적기억력의저하가 45명으로전체의 75% 였고, 물건둔곳을잊어버리거나방문했던장소나길을잊어버리는등의시각적기억력의저하는 32 명으로전체의 53.3% 였으며언어와시각적기억력저하를동시에호소한경우는 29명으로 48.3% 였다. 이중 7명 (11.7%) 은주관적인기억력저하의호소외에도이름대기의장애, 발음장애, 이해력저하와같은언어기능의미약한저하나주위사람들에의해인지된성격변화또는행동이나사고의느려짐등으로내원하였으나본연구에서제시한경도인지장애의기준에합당하여포함되었다. Subtype Figure 1. The prevalence of depression in the subtypes of mild cognitive impairment. Depression judged by 24 or more geriatric depression scale (GDS) score is most prevalent in multiple domains slightly impaired MCI. MCI; mild cognitive impairment 3. 각아형별환자비율과신경심리검사소견및우울증과성격변화빈도 (Table 5) 각아형별로보면, amnestic MCI 가 13 명 (21.7%), single nonmemory domain MCI 가 24명 (40.0%), 그리고 multiple domains slightly impaired MCI 가 23 명 (38.8%) 이었다. 아형간에평균 K-MMSE 점수는 amnestic MCI, single nonmemory domain MCI, multiple domains slightly impaired MCI 가각각 27.8±1.52, 27.5±1.32, 27.1±1.32 점으로서통계학적으로유의한차이가없었다. Amnestic MCI 중언어적기억력 (verbal memory) 과시각적기억력 (visual memory) 이저하된경우가각각 5명, 4명이었고, 모두저하된경우가 4명이었다. Single nonmemory domain MCI' 24 명중전두엽기능이저하된경우가 21 명으로대부분을차지했고, 그밖에시각공간지각력의저하가 2명, 언어기능의저하가 1명이었다. 'multiple domains slightly impaired MCI 중기억영역의저하가포함된경우가 21명으로대부분이었고 2명만이전두엽기능과시각공간능의저하가있엇다. 노인우울척도 24점이상으로판단한우울증은 10명 (16.7%) 이었는데, 그중 3명 (30%) 이 amnestic MCI 에, 7명 (70%) 이 multiple domains slightly impaired MCI 였고 single nonmemory domain MCI 에해당하는경우는없었으며, 통계학적으로우울증이 multiple domains slightly impaired MCI 에서유의하게높은비율로나타났다 (Fig. 1). 성격의변화를보인경우는 3명이었는데모두 single nonmemory domain MCI 이면서전두엽기능이저하되어있었고, 성격변화의내용중공통적인것은불안증이었으며, 2명은사소한일에심하게걱정하고염려하는증상을보였고 1명은집중력의현저한저하를나타냈다. Table 5. Clinical and neuropsychological features of subtypes of mild cognitive impairment No. of patients (ratio) K-MMSE Declined cognitive domain Depression Personality change Amnestic MCI 13 (21.7%) 27.8±1.52 verbal visual both Single nonmemory domain MCI 24 (40.0%) 27.5±1.32 frontal visuospatial language 21 a Multiple domains slightly impaired MCI 23 (38.8%) 27.1±1.32 memory+ memory- MCI; mild cognitive impairment, K-MMSE; Korean version of mini-mental state examination, *p<0.01, p< b J Korean Neurol Assoc Volume 23 No. 3,

5 임준성김정은백민재박성호김상윤 4. 뇌영상소견 뇌 MRI 는검사를거부한환자를제외하고 37명만검사하였는데, amnestic MCI 7명, single nonmemory domain MCI 15 명, multiple domains slightly impaired MCI 15 명으로서아형군별로비교적고르게포함되었다. 뇌 MRI 를한 37명중 14명은연령을고려하였을때정상소견을보였다. 연령에의한일반적인변화보다심하다고판정된측두엽위축이 2명 (5.4%) 에서관찰되었고다른 2명에서전반적인뇌피질위축이있었다. 한환자에서는양쪽전두엽에심한위축을보였는데전두엽기능의현저한저하를보이는 single nonmemory domain MCI 에속했다. 18명에서 1개이상의열공경색을포함하는백질부위고신호강도가보였는데이중 7 명이 multiple domains slightly impaired MCI, 11명이 single nonmemory domain MCI 에속했고 amnestic MCI 에속하는경우는없었으며, 시상경색이나회백질의미세출혈이동반된경우가각각 1명이었다 (Fig. 2). SPECT 를한 8명중 2명만이정상이었고 3명은좌측측두 / 두정엽부위의관류저하 ( 이중 1명은 diamox 에우측측두 / 두정엽에 vascular reserve 감소, 다른 1명은좌측전두엽후방 / 우측두정엽에도관류저하소견보임 ), 1명은우측측두 / 두정엽, 그리고 1명은우측측두엽에관류저하를보였고나머지 1명은 nonspecific diaschisis 소견이었다. PET 를한 6명중 1명은 SPECT 에서좌측전두 / 측두엽및양측두정엽에서관류저하를보인예에서시행하였는데좌측측두 / 두정엽부위만이대사저하가있었다. 나머지 5명중 1 명이좌측, 다른 1명이양측측두 / 두정엽대사저하가있었고그외의 3명도모두비특이적으로 Subtype Figure 2. The vascular factors in the subtypes of mild cognitive impairment. White matter hyperintensities on MRI are most frequently detected in the single nonmemory domain MCI group. WMH; white matter hyperintensities. MCI; mild cognitive impairment 여러부위에다양한정도의대사저하를보였으며정상소견을보인경우는없었다. 뇌 MRI 소견이정상이면서 SPECT 에서이상을보인경우는 1명, PET 에서이상을보인경우는 3명이었다. 5. 아포지방단백유전자형과대립유전자빈도 (ApoE genotype and allele frequency) 이들중 14명 ( amnestic MCI 5명, single nonmemory domain MCI 5명, multiple domains slightly impaired MCI 4명 ) 에대해알쯔하이머병의위험인자인 ε4 allele 를보기위해아포지방단백 E 유전자형 (apolipoprotein E genotype) 을측정하였고, 이미제시된바있는한국정상인유전자형의분포와비교하였는데대립유전자 (allele) 빈도는 ε4, ε3, ε2 가각각 35.7%, 60.7%, 3.6% 였다. 절반이상 (57.1%) 이 ε4 대립유전자를보유하였고그중 2명 (14.28%) 이 ε4 동종접합체 (homogygote) 였다. 단지 1명만이하나의 ε2 대립유전자를보유하였고 5명 (35.71%) 이 ε3 동종접합체였다. 고찰 경도인지장애에대한개념이생기고이에대한연구가활발해지면서경도인지장애군이치매로진행할위험성이큰군으로확인되었으며이들을조기에발견하여주기적으로관찰하고필요시약물치료를하여진행속도를최대한지연시킬수있느냐하는문제는치매를보이는퇴행성질환자들뿐만아니라그들을돌보는가족, 사회에까지도중요한문제이다. 5-7 하지만아직까지도경도인지장애에대한정의나기준이확실히정립되어있지않아서연구마다유병률과치매로의진행률이각기다르고, 진단기준이명확하지못해환자진료에적용하기어렵다. 국내에서도과거에는경미한기억장애를가진환자가조기에병원을찾는경우가적었기때문에아직까지실제임상경험을바탕으로제안된기준조차없다. 하지만최근에경미한인지기능저하를가진환자가초기에진료를받는경우가많아지고, 노인인구가늘어나인지기능이저하되는치매및퇴행성질환의빈도가증가추세에있으며, 이에대한치료약제의개발이가속화됨에따라이러한경도인지장애에대한개념의정립및기준설정이중요하다고생각된다. 알쯔하이머병의전단계에있는환자군을찾아내기위해현재의경도인지장애의개념을공유하는여러정의들이있다 년에 benign senescent forgetfulness 가제안되었는데기준 352 J Korean Neurol Assoc Volume 23 No. 3, 2005

6 이모호하다고비판받았고, 1986 년에제안된 age-associated memory impairment 는임상에적용하기힘들고교육수준이높은사람은잘포함되지않는단점을보였다 그후 1982 년에 Global Deterioration Scale 이 3점인군을 mild cognitive decline 으로, 같은해에 Clinical Dementia Rating 점수가 0.5 인군을 questionable dementia 로명명했지만이들역시적합하지못했으며, 1994 년에 International Psychogeriatric Association 에서 age-associated cognitive decline' 이란용어를제안하기도했다. 최근에 Canadian Study of Health and Aging 에서 Cognitive impairment-no dementia (CIND) 개념을제안하고이를통한연구를했지만섬망, 뇌종양, 정신분열증등치매로진행하지않는질환군이상당부분포함되는단점이발견되었다. 11,13 그후 amnestic MCI criteria 가제안되었는데이는기억력저하를호소하는경우객관적인검사에서연령과교육수준에비해실제로기억력저하가있지만전반적인인지기능은정상범위이고, 일상생활에장애가없어치매에는합당하지않은상태를정의하는기준이었다. 이기준에맞는군을대상으로한추적연구에서매년약 10~15% 가알쯔하이머병으로진행하여결국 6년후에는 80% 정도가알쯔하이머병으로진행하는결과를보여알쯔하이머병의고위험군을찾아내기에우수한기준임을입증하였다. 1,4,5 그러나이연구에서일부는인지기능의저하가더이상진행되지않고그대로이거나또는오히려호전되는양상을보였고이러한결과를통해연구자들은경도인지장애가알쯔하이머병으로진행할수있는고위험군이많이포함되어있는것은사실이지만그외의다른다양한상태나질환들이섞여있는다양하고이질적인집단임을알게되었다. 14,15 연구자들이혼란을겪어왔던부분은크게두가지인데첫째는저하되는인지기능영역이과연기억영역이어야만하는가에대한논란이고, 둘째는인지기능저하를평가할때과연그기준이연령이나학력을고려한평균치여야하는가에대한연구자들간의불일치였다. 그후실제로기억외의다른인지기능영역, 즉시각공간지각력, 전두엽기능, 언어기능등의저하가기억장애보다선행또는동반될수있고이러한기억외의인지기능의저하도알쯔하이머병또는그외의치매로진행할가능성이높음이입증되면서경도인지장애에대한개념및기준정립은새로운전환을맞게되었다. 최근에지금까지의시행착오를고려한경도인지장애의기준을마련하였는데그내용의골자는경도인지장애의아형에대한분류이며 amnestic MCI, multiple domains slightly impaired MCI, single nonmemory domain MCI 으로나누었 다. 이기준은연령과교육수준을고려한평균을바탕으로인지기능의저하를판단하고, 기억외의인지기능영역의기능저하도고려하는점이있어이전의경도인지장애기준의단점을극복하였으며알쯔하이머병뿐만아니라전두측두엽치매, 루이체치매, 피질하혈관성치매등으로진행할위험이큰환자들까지도경도인지장애군에포함시키는진일보한기준으로평가되고있다. 4 결국경도인지장애는질환명이아니라경미한인지기능의저하를나타내는다양한군들이모여있는이질적인집합체 (heterogenous condition) 로서정상인지기능상태와초기치매상태사이에명확한경계없이존재하는중간상태로서임상양상뿐만아니라원인질환에서도그러한이질성및다양성을보인다. 그래서실제임상에서경도인지장애에포함되는질환들은알쯔하이머병이나그밖의다른치매질환의전단계뿐아니라우울증및정신질환, 장기간지속되는간질, 신체장애, 향정신약에의한부작용, 벤조디아제핀의과다사용, 베르니케뇌증, 해마경화증등이있을수있다. 16 이러한경도인지장애를임상에적용해보면, 먼저환자나보호자가기억력또는그밖의인지기능저하를주관적으로호소할때자세한병력청취와진찰을한후연령에비해어느정도의인지기능의저하가있다고생각되지만, 간이신경심리검사를하였을때전반적인지기능이비교적정상범위이고, 면담과일상생활의장애가없어치매상태는아니라고판단될경우, 이때환자의상태가경도인지장애가능성이있다고의심하는것이중요하며경도인지장애여부및아형의결정을위해신경심리학적검사를하여기억력, 시각공간지각력, 언어기능, 전두엽기능영역중저하된영역이있는지, 있다면어느영역인지를알아보아야한다. 17 정신상태검사는주로 mini-mental state examination (MMSE) 로검사하고연령과교육수준을고려한평균과표준편차를이용해평균에서표준편차의 n배수를뺀값 (mean-nsd) 이상일경우를일단경도인지장애의후보군으로생각하고, 신경심리학적검사에의해서저하된인지영역의결정은각영역을나타내는검사를결정하고그검사결과가연령과교육수준을고려한평균에서표준편차의 n배수를뺀값 (mean-nsd) 이하일경우그영역이저하되어있다고결정할수있다. 17,18 저자들은경도인지장애및그아형에대한정의를바탕으로실제임상적용이가능한활용기준 (working criteria) 을만들었고이기준에맞는 60명을선정하였다. CDR 과 GDS 를척도로사용하여 CDR 0.5 이고 GDS 2 또는 3인군을선정하였는데 CDR 0.5 군에해당하는수는 289 명이었고그중 GDS 2, 3, 4는각각 168 명, 116 명, 5명이었다. 한지역의 65세이상의주민을 J Korean Neurol Assoc Volume 23 No. 3,

7 임준성김정은백민재박성호김상윤 대상으로최근연구에서 CDR 0.5 에해당하는수는전체대상의 30.2% 였고경도인지장애는 4.9% 로조사되었는데, 본연구에서도 CDR 0.5 군에는경도인지장애보다오히려 'very mild AD' 가더많이포함됨을알수있다. 19 본연구에서전체 60 명중여자가 38 명으로남자보다통계적으로유의하게많았지만각아형별성비는차이가없었다. 평균연령은 single nonmemory domain MCI 에서가장높았고교육연수는 multiple domains slightly impaired MCI 에서가장적었지만세아형간에통계학적으로유의한차이는없었다. Single nonmemory domain MCI 가 24 명 (40%) 으로가장많았는데그중전두엽기능이저하된경우가 21명으로대부분을차지했고, multiple domains slightly impaired MCI' 가 23 명 (38.8%) 으로그뒤를이었으며, amnestic MCI' 가 13명 (21.7%) 으로가장적었다. 이는최근일반인구를대상으로한연구에서보인경도인지장애아형별유병률과유사하다. 20 3년간의추적연구에서각아형중알쯔하이머병으로의진행률이가장높은것은 multiple domains slightly impaired MCI 로서 75.5% 가알쯔하이머병으로진행하였고, amnestic MCI 는 33.5%, single nonmemory domain MCI 는 10.0% 였다. 21 Multiple domains slightly impaired MCI 가알쯔하이머병으로의진행률이가장높은것은 amnestic MCI 가진행되어 multiple domains slightly impaired MCI 로발전한다고생각해볼수있지만본연구에서아형간의평균 K-MMSE 점수가차이가없는점으로보아설득력이부족하고 multiple domains slightly impaired MCI 자체가알쯔하이머병으로의진행률이높은군일가능성이있다고생각된다. 본연구대상의각유형별진행양상및예후에대한추적조사및그요인분석이향후필요할것으로생각된다. 전체의 17%(10 명 ) 에서노인우울척도가 24점이상으로우울증이의심되었는데그중 7명이 multiple domains slightly impaired MCI' 에속해있어가장높은비율을보였다. 경도인지장애에서우울증이흔하고, 그외에도흥분증, 불안증, 무감동등의증상이나타날수있는데, 이러한행동및정신증상이치매로의진행가능성을높이는것으로보고된바있어본연구에서우울증이 multiple domains slightly impaired MCI' 에많은것이이아형의높은치매로의진행률과관계가있을수있다고생각된다. 또한성격변화를보인모든경우가전두엽기능이저하된 single nonmemory domain MCI 였는데, 이들이과연전두측두엽치매로진행할것인지는추적검사를통해알아보아야할과제이다. 뇌 MRI 에서소혈관질환 (small vessel disease) 을의미하는백질변성및열공경색이 single nonmemory domain MCI 에 서가장높은빈도로나타난것은이아형중전두엽기능의저하를보인경우가대부분인것과연관이있는것으로보이며, multiple domains slightly impaired MCI 중에도약반정도에서이러한변화가보였다. 경도인지장애아형중 single nonmemory domain MCI 와 multiple domains slightly impaired MCI 의경우에는피질하허혈성혈관질환 (subcortical ischemic vascular disease) 을반드시의심해보고고혈압, 심장질환및고지혈증등의혈관질환의위험인자를조사할필요가있다고생각된다. 14명에서검사한아포지방단백 (apolipoprotein E) 의대립유전자형 (allele) 검사에서반이상 (57.1%) 이 ε4 보유자로나와한국정상인의 18.8% 에비해현저히높은비율을보였다. 이는이전의 amnestic MCI' 를대상으로했던연구와유사한결과로서, 경도인지장애가알쯔하이머병의고위험군임을보여준다고할수있다. 22 기억및인지장애를호소하는환자를진료할때, 경도인지장애가주로알쯔하이머병을포함한치매의전단계를의미하고, 그밖의우울증이나뇌혈관성질환등의여러원인질환을포함하는이질적인상태라는개념을가지고이를임상에적용하는것이필요하다. 저자들은이제까지의정의와기준을바탕으로경도인지장애의실제임상활용기준 (working criteria) 을제시하였고이를통해경도인지장애군이세가지임상아형으로구분됨을확인하였으며그대체적인비율및임상적특징을알아보았다. 향후이들에대한정기적인추적을통해각아형별예후를분석하여알쯔하이머병또는그외의치매로진행하는빈도와위험인자등을알아보는것이중요할것이다. REFERENCES 1. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Kokmine E, Tangelos EG. Aging memory, and mild cognitive impairment. Int Psychogeriatri 1997;9 Suppl 1: McDowell I. Alzheimer's disease; insights from epidemiology. Aging (Milano) 2001;13: Linn RT, Wolf PA, Bachman DL, Knoefel JE, Cobb JL, Belanger AJ, et al. The preclinical phase of probable Alzheimer s disease. A 13-year prospective study of the Framingham cohort. Arch Neurol 1995;52: Petersen RC, Doody R. Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58: Petersen RC, Smith GE, Warring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterisation and outcome. Arch Neurol 1999;56: Tierney MC, Szalai JP, Snow WG, Fisher RH. The prediction of Alzheimer's disease: the role of patients and informant perceptions 354 J Korean Neurol Assoc Volume 23 No. 3, 2005

8 of cognitive deficits. Arch Neurol 1996;53: Bowen J, Teri L, Kukull W, McCormick W, McCurry SM, Larson EB. Progression to dementia in patients with isolated memory loss. Lancet 1997;349: Kral VA. Senescent forgetfulness: benign and malignant. Can Med Assoc J 1962;86: Blessed G. Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of the elderly subjects. Br J Psychiatry 1968;114: Crook T, Bartus RT, Ferris SH. Whitehouse P, Cohen GD, Gershon S. Age-associated memory impairment:proposed diagnostic criteria and measures of clinical change-report of a National Institute of Mental Health work group. Dev Neuropsychol 1986;2: Ebly EM, Hogan DB, Parhad IM. Cognitive impairment in the nondemented elderly. Results from Canadian Study of Health and Aging. Arch Neurol 1995;52: Nielsen H, Lolk A, Kragh-Sorensen P. Age-associated memory impairment-pathological memory decline or normal aging? Scand J Psychology 1998;39: Tuokko HA, Frerichs, Kristjansson. Cognitive impairment, no dementia: concepts and issues. Int Psychogeriatr 2001;13 Suppl 1: Wolf H, Grunwald M, Ecke GM, Zedlick D, Bettin S, Dannenberg C, et al. The prognosis of mild cognitive impairment in the elderly. J Neural Transm Suppl 1998;54: Ingles JL. Fisk JD, Merry HR, Rockwood K. Five-year outcomes for dementia defined solely by neuropsychological test performance. Neuroepidemiology 2003;22: Wahlund LO, Pihlstrand E, Jonhagen ME. Mild cognitive impairment: experience from a memory clinic. Acta Neurol Scand 2003;179: Palmer K, Backman L, Winblad B, Fratiglioni L. Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study. BMJ 2003;326: Small BJ, Viitanen M, Backman L. Mini-Mental State Examination item scores as predictors of Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. J Gerontol A Biol Sci 1997;52: Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov 2003;2: Busse A, Bischkopf J, Riedel-Heller SG, Angermeyer MC. Subclssifications for mild cognitive impairment; prevalence and predictive validity. Psychol Med 2003;33: Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment--beyond controversies, towards a consensus; report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256: Nicola TL, Matthias R, Alexander D, Alexander FK. Primary degenerative mild cognitive impairment: study population, clinical, brain imaging and biochemical findings. Dement Geriatr Cogn Disord 2001;12: J Korean Neurol Assoc Volume 23 No. 3,

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