임상노인의학회지 : 제 13 권제 4 호 Korean J Clin Geri 2012;13(4):196-202 대혈관혈관성치매와소혈관혈관성치매의행동심리적증상의차이 김명국, 유봉구 고신대학교의과대학신경과학교실 Differences of Behavioural and Psychological Symptoms between Large-Vessel and Small-Vessel Vascular Dementia Meyung-Kug Kim, M.D., Ph.D., Bong-Goo Yoo, M.D., Ph.D. Department of Neurology, Kosin University College of Medicine, Busan, Korea Background: Behavioral and psychological symptoms of dementia (BPSD) are common manifestations of dementing disorders. Some studies have sought to identify specific BPSD that distinguish Alzheimer s dementia from vascular dementia. We investigated the differences of BPSD between large-vessel vascular dementia and small-vessel vascular dementia. Methods: The BPSD of 77 patients with vascular dementia determined using the Korean version of the neuropsychiatric inventory (K-NPI). The patients were classified as having large-vessel vascular dementia or small-vessel vascular dementia based on MRI. Results: The BPSD were reported in 73% of the patients with vascular dementia. Apathy/indifference was the symptom that was reported most often in both large-vessel vascular dementia and small-vessel vascular dementia groups, followed by depression/dysphonia and anxiety. Patients with small-vessel vascular dementia reported more and severe agitation/aggression than patients with large-vessel vascular dementia (P=0.017). Conclusion: The BPSD are frequent in vascular dementia. Patients with large-vessel vascular dementia and small-vessel vascular dementia reveal different BPSD profiles, especially more agitation/aggression in small-vessel vascular dementia. Key Words: Behavioral and psychological symptoms of dementia, Vascular dementia, Apathy, Agitation 서 론 치매의행동심리적증상 (behavioral and psychological symptoms of dementia, BPSD) 은처음치매로진단받은환자의 2/3에서, 진행된치매의 70 90% 에서흔히나타나는증상이다. 1) BPSD는치매환자의예후, 이환율, 교신저자 : 유봉구, 부산시서구암남동 34, 602-702, 고신대학교의과대학신경과학교실 Tel: 051-990-6364, Fax: 051-990-3077, E-mail: ybg99@naver.com - 196 -
김명국 유봉구 : 대혈관혈관성치매와소혈관혈관성치매의행동심리적증상의차이 사망률, 시설입소등에중요한요인이되고, 부양부담 (care burden) 에도많은영향을미친다. 1,2) BPSD는이상행동과정신증상으로나누는데, 이상행동은초조 / 공격성 (agitation/aggression), 이상행복감 / 들뜸 (euphoria/elation), 탈억제 (disinhibition), 무감동 / 무관심 (apathy/indifference), 화를잘냄 / 정서적불안정 (irritability/lability), 비정상적인운동행동 (aberrant motor behavior), 수면중행동 (sleep/night-time behavior), 식욕 / 식습관의변화 (appetite/eating disorder) 등이있고, 정신증상에는우울 / 낙담 (depression/dysphonia), 불안 (anxiety), 망상 (delusion), 환각 (hallucination) 등이있다. 이들증상은계속변화하며, 평가는부양자의정보에의존해야한다. BPSD는대부분의치매환자에서나타나는데치매의아형이나진행정도에따라차이가있다. 3-9) 그러나지금까지의연구들은대부분각치매아형별로 BPSD의차이에대한것이대부분이었고, 혈관성치매중대혈관-혈관성치매 (large-vessel vascular dementia) 와소혈관-혈관성치매 (small-vessel vascular dementia) 에서의 BPSD 차이에대한연구는매우드물다. 10) 이에저자들은대혈관혈관성치매와소혈관혈관성치매의 BPSD 에서어떤차이가있는지를알아보고자하였다. 방 법 1. 연구대상 2010년 1월부터 2012년 7월까지인지기능장애를주소로본원을방문한 116명의혈관성치매환자들을대상으로하였다. 혈관성치매는 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) 11) 의치매정의를만족하고, National Institute of Neurological Disorders and Stroke Association International pour la Recherche et l'enseignement en Neurosciences (NINDS-AIREN) 12) 의 probable 또는 possible 혈관성치매의정의를충족하는환자로하였다. 원발성신경퇴행성질환, 3개월이내뇌졸중의병력, 주요우울증이나다른정신과적문제가있는경우, 갑상선기능저하증, 악성종양, 약물남용, 두부손상등이있는환자는제외하였다. 또한의식저하, 섬망, 심한언어상실증이나감각운동장애등이있어신경심리검사에지장을주는환자도제외하였다. 이들을제외하고적어도 3개월이상환자와동거했고, 질문에대한이해와응답이가능한부양자가동의서에서명한 77명을연구대상으로하였다. 2. 조사방법환자의성별, 나이, 학력, 유병기간과고혈압, 당뇨병, 고지질혈증등의과거력및흡연이나음주유무등을조사하였다. 전반적인치매상태와진행정도를평가하기위해한국판간이정신상태검사 (Korean version of mini-mental status examination, K-MMSE) 13) 와임상치매척도 (Clinical Dementia Rating, CDR) 14) 를사용했고, BPSD 평가를위해 12항목으로구성된한국형 neuropsychiatric inventory (K-NPI) 15) 를이용하였다. K-NPI는환자와같이살거나, 일주일에 3회이상환자를만나서환자의상태변화를잘아는보호자를대상으로조사하였다. 특정이상행동이있는경우빈도 (0 4점) 와심한정도 (0 3점) 를각각선택하여곱해서합성점수 (composite score) 를구했다. 12개항목의합성점수를모두합하여총 K-NPI 점수로하였다. 뇌자기공명영상 (MRI) 를이용하여대혈관혈관성치매와소혈관혈관성치매로나누었다. 대혈관혈관성치매는우성반구의전략적대혈관뇌경색증이나양측성대혈관뇌경색증이있는경우로, 소혈관혈관성치매는 MRI에서다발성열공성뇌경색, 백질고신호강도가적어도백질의 1/4 이상침범한경우또는양측성 - 197 -
임상노인의학회지제 13 권제 4 호 2012 시상병변이있는경우로하였다. 16) 그외에바텔지수 (Barthel index), 도구적일상생활력 (instrumental activity of daily living, IADL), 노인우울척도 (geriatric depression scale) 를조사하였다. 3. 통계분석자료의분석은 SPSS (version 12.0) 를이용하였다. 환자군의임상적특성중연속성변수는 t-검정을, 범주성변수는 chi-square 검정을이용했으며, 기대도수가 5 이하인경우는 Fisher s exact 검정을사용하여분석하였다. 양군의 K-NPI 항목의빈도는 chi-square 검증으로, 중증도의비교는 Manne-Whitney U tests를이용했다. 유의수준은 P<0.05로하였다. 결 과 총 77명의환자들중대혈관혈관성치매 35명 (45.5%), 소혈관혈관성치매 42명 (54.5%) 이었다. 성별, 나이, 고혈압, 당뇨병, 고지질혈증, 흡연, 음주, 교육수준, 유병기간및치매검사척도점수들을제시하였다 (Table 1). 대혈관혈관성치매는남자가, 소혈관혈관성치매는여자가더많았다. 연령분포는 52 87세로평균나이는대혈관혈관성치매 64.2±10.2세, 소혈관혈관성치매 69.9±7.0세로소혈관혈관성치매군에서높았다 (P=0.019). K-MMSE, CDR, IADL은두군간에차이가없었으나, 흡연은대혈관혈관성치매군에서더많았다 (P=0.044). 교육수준이나치매의유병기간은차이가없었다. 총 K-NPI 점수는대혈관혈관성치매 7.2±9.2, 소혈관혈관성치매 16.7±14.2로통계학적으로유의한차이는없었지만소혈관혈관성치매군에서점수가높았다. BPSD는혈관성치매환자의 73% 에서나타났다. 대혈관혈관성치매군은무감동 / 무관심 (48%) 이가장높은빈도를보였고, 우울 / 낙담 (34%), 불안 (34%), 화를잘냄 / 정서적불안정 (23%), 식욕 / 식습관의변화 (20%), 탈억제 (17%), 비정상적인운동행동 (14%), 수면중행동 (14%) 순으로나타났다 (Table 2). 이상행복감 / 들뜸 (8%), 초조 / Sex (male/female) Age (year) Hypertension Diabetes mellitus Hyperlipidemia Smoking Alcohol Education duration (year) Symptom duration (month) K-MMSE CDR Barthel index Instrumental ADL Geriatric depression scale Total K-NPI score Table 1. Demographics and characteristics of patients with vascular dementia Large-vessel VaD (n=35) Small-vessel VaD (n=42) P value 20/15 64.2±10.2 25 14 11 14 15 6.8±4.9 20.0±16.2 18.4±5.8 0.8±0.3 19.1±3.6 5.8±7.6 18.6±6.3 7.2±9.2 17/25 69.9±7.0 31 15 9 8 11 5.7±5.0 17.9±11.5 16.9±5.6 1.0±0.5 16.4±4.4 9.6±12.4 19.1±6.2 16.7±14.2 0.019 0.816 0.701 0.322 0.044 0.126 0.327 0.794 0.211 0.094 0.001 0.348 0.796 0.158 Values are labeled as mean±sd. VaD: vascular dementia, K-MMSE: Korean version of mini-mental status examination, CDR: clinical dementia rating, ADL: activities of daily living, K-NPI: Korean version of neuropsychiatric inventory. - 198 -
김명국 유봉구 : 대혈관혈관성치매와소혈관혈관성치매의행동심리적증상의차이 Delusion Hallucination Agitation/aggression Depression/dysphonia Anxiety Euphoria/elation Apathy/indifference Irritability/lability Disinhibition Aberrant motor behavior Sleep/night-time behavior Appetite/eating disorders Table 2. Prevalence of individual K-NPI symptoms in small-vessel VaD and large-vessel VaD Large-vessel VaD (n=35) Small-vessel VaD (n=42) P value 1 (2%) 2 (6%) 3 (8%) 12 (34%) 12 (34%) 3 (8%) 17 (48%) 8 (23%) 6 (17%) 5 (14%) 5 (14%) 7 (20%) 6 (14%) 4 (9%) 13 (31%) 22 (52%) 16 (38%) 5 (12%) 28 (67%) 12 (29%) 11 (26%) 8 (19%) 14 (33%) 14 (33%) 0.084 0.537 0.017 0.074 0.731 0.635 0.111 0.430 0.344 0.581 0.055 0.194 Data were compared using chi-square tests. K-NPI: Korean version of neuropsychiatric inventory, VaD: vascular dementia. Delusion Hallucination Agitation/aggression Depression/dysphonia Anxiety Euphoria/elation Apathy/indifference Irritability/lability Disinhibition Aberrant motor behavior Sleep/night-time behavior Appetite/eating disorders Table 3. Severity of K-NPI symptoms in small-vessel VaD and large-vessel VaD Large-vessel VaD (n=35) Small-vessel VaD (n=42) P value 0.03±0.17 0.06±0.27 0.31±1.21 0.83±1.40 1.00±1.85 0.40±1.61 1.63±2.39 0.74±1.82 0.57±1.56 0.49±1.48 0.46±1.48 1.11±2.41 0.38±1.17 0.38±1.53 1.02±1.91 1.40±1.90 1.29±2.21 0.40±1.53 2.45±3.17 1.24±2.31 0.79±1.77 0.93±2.45 1.24±2.76 1.17±1.99 0.078 0.509 0.019 0.090 0.630 0.685 0.164 0.375 0.378 0.531 0.064 0.354 Statistics were performed using Mann-Whitney U tests. Values are labeled as mean±sd. K-NPI: Korean version of neuropsychiatric inventory, VaD: vascular dementia. 공격성 (8%), 환각 (6%), 망상 (2%) 등은드물었다. 소혈관혈관성치매군에서는대혈관혈관성치매와마찬가지로무감동 / 무관심 (67%) 이가장흔했고, 우울 / 낙담 (52%), 불안 (38%), 수면중행동 (33%), 식욕 / 식습관의변화 (33%), 초조 / 공격성 (31%), 화를잘냄 / 정서적불안정 (29%), 탈억제 (26%), 비정상적인운동행동 (19%), 망상 (14%), 이상행복감 / 들뜸 (12%), 환각 (9%) 순의빈도를보였다. 두군간에각 K-NPI 항목을비교했을때초조 / 공격성이소혈관혈관성치매에서유의하게높은빈도로 (P=0.017), 더심하게나타났다 (Table 3) (P=0.019). 고 찰 본연구는혈관성치매환자에서대혈관혈관성치매와소혈관혈관성치매의 BPSD 차이에대해알아보았 - 199 -
임상노인의학회지제 13 권제 4 호 2012 다. 환자의 K-NPI 항목각각의유병율및합성점수와총점을통하여양군간에어떤차이가있는지를살펴보았다. 본연구에포함된환자군은 3년이하의치매유병기간을가진환자가약 90% 였고, CDRS 점수가높지않아경증이나중등도의환자군이고, 교육수준이서구보다는낮은특징을가지고있다. 따라서이러한점을고려해서결과를해석해야할것이다. BPSD는많은치매환자들에서흔히나타나는증상이며경과에도많은영향을미친다. 치매아형에따른 BPSD의차이에대한여러연구들이있는데, 알츠하이머병이혈관성치매보다 BPSD의빈도나정도가더심하다는보고도있고반대의경우도있다. 3,8) BPSD에서로차이가나기때문에 BPSD로두치매아형을감별하는데도움이될수도있다. 17,18) BPSD는치매의중증도와도관련이있어심한치매에서더흔하고심하게나타난다. 19) 치매가심해지면 BPSD의총점수보다초조 / 공격성과비정상적인운동행동같은특정항목과관련이있다. 20) BPSD의심한정도는치매아형과무관하고치매의중증도와관련이있다는보고도있다. 21) 이렇게다양한결과를보이는데, 한가지공통적인점은무감동 / 무관심과우울 / 낙담은혈관성치매에서자주그리고심하게나타난다. 3-6,20,22) 본연구에서도대혈관혈관성치매, 소혈관혈관성치매모두에서무감동 / 무관심이가장많았고, 다음으로우울 / 낙담과불안이흔히나타났다. 이는관자엽과마루엽기능장애가잘나타나는알츠하이머병과달리혈관성치매는이마엽이영향을많이받기때문에나타나는현상으로여겨진다. 무감동 / 무관심은목표지향적작용을조절하는이마앞엽겉질 (prefrontal cortex) 과바닥핵및시상, 둘레계통 (limbic system) 을연결하는신경망이백질변성이나바닥핵과시상의열공경색증으로인해차단되어발생한다. 23) 혈관성치매자에서대혈관혈관성치매는백질변성에의한신경연결의단절때문에, 소혈관혈관성치매는바닥핵, 시상등을침범한병변으로인해증상이발생한것으로여겨진다. 무감동 / 무관심다음으로우울 / 낙담이나불안이흔히나타났는데, 이는 혈관성우울가설 (vascular depression hypothesis) 로설명될수있다. 겉질밑혈관성병변은노년기및뇌졸중후우울증과관련이있는데환자의약 30% 에서나타난다. 24-26) 뇌병변자체나이로인한장애때문에생긴정신적충격이환자의기분에영향을주었을것이라생각되지만이에대한연구는더진행되어야할것이다. 본연구에서노인우울척도가대혈관혈관성치매와소혈관혈관성치매에서각각 18.6±6.3, 19.1±6.2로큰차이없이높게나타났다. 한연구에서는대혈관과소혈관혈관성치매에서총 NPI 점수는유사했으나대혈관혈관성치매군에서초조 / 공격성과이상행복감 / 들뜸이, 소혈관혈관성치매군에서는무감동 / 무관심, 환각, 비정상적인운동행동이더흔하고심했다. 10) 본연구에서는초조 / 공격성이소혈관혈관성치매에서유의하게높은빈도를보였으나, 이를제외한나머지증상들은두군간의유의한차이는없었다. 환자군이적어서통계적유의수준에도달하지는못했으나망상과수면중행동이소혈관혈관성치매군에서높은경향을보였다. 초조 / 공격성을제외하고유의한차이는없었으나, 모든증상들이소혈관혈관성치매군에서더높은빈도로, 더심하게나타났다. 총 K-NPI 점수도소혈관혈관성치매군에서더높았다. 이러한차이점은환자군의임상적특징이다르고, 환자와부양자의교육수준이나문화적차이, 부양자의환자와의관계의차이등이영향을미칠것이다. 치매환자의 BPSD에대한연구에서보고자마다결과에많은차이가있다. 이러한차이점이생기는이유는 BPSD가부양자의관찰로간접적으로평가하는것이라주관적일수있고, 보호자의사회문화적상이성, 치매의진행정도에따라차이가날수있으며, 증상의변화가심하기때문일수도있다. 3) 또한병리조직학적검사없이임상증상과 MRI 소견만으로환자를분류했기때문에순수혈관성치매가아닌알츠하이머병이나다른신경퇴행성질환이포함되었을가능성도고려해야한다. 본연구의제한점으로는환자군의수가부족했고, 부양자와치매의중증정도에따른분석이이루어지지않았으며, 신경이완제같은 BPSD에영향을미칠수있는약물복용에대한고려가없었고, 단일기관의 - 200 -
김명국 유봉구 : 대혈관혈관성치매와소혈관혈관성치매의행동심리적증상의차이 연구라는점이있다. 향후이것들을보완한연구가필요한실정이다. 결론적으로혈관성치매환자에서 BPSD는흔하게나타나며, 무감동 / 무관심, 우울 / 낙담, 불안의빈도로 BPSD가나타난다. 소혈관혈관성치매에서대혈관혈관성치매보다초조 / 공격성이심하고흔하게나타났다. 참고문헌 1. Teri L. Behavior and caregiver burden: behavioral problems in patients with Alzheimer disease and its association with caregiver distress. Alzheimer Dis Assoc Disord 1997;11 Suppl 4:S35-8. 2. Yoo BG, Kim EG, Kim JW, Kim TY, Park KW, Sung SM, et al. Relationship between behavioral and psychological symptoms of dementia and caregiver burden. Dement Neurocognitive Disord 2008;7:1-9. 3. Kim TY, Kim SY, Kim EG, Kim JW, Park KW, Sung SM, et al. The differences of behavioral and psychological symptoms in the patients of Alzheimer's disease and vascular dementia. J Korean Neurol Assoc 2006;24:458-64. 4. Fuh JL, Wang SJ, Cummings JL. Neuropsychiatric profiles in patients with Alzheimer s disease and vascular dementia. J Neurol Neurosurg Psychiatry 2005;76:1337-41. 5. Srikanth S, Nagaraja AV, Ratnavalli E. Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer s disease, vascular dementia and frontotemporal dementia. J Neurol Sci 2005;236:43-8. 6. 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;18:215-20. 7. 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;8:89-95. 8. Koh SB, Yang DW, Chung SW, Choi YB, Kim BS. The different patterns of behavioral derangements in subcortical vascular dementia and Alzheimer s disease. J Korean Neurol Assoc 2002;20:353-8. 9. 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;22:34-9. 10. Staekenborg SS, Su T, van Straaten EC, Lane R, Scheltens P, Barkhof F, et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J Neurol Neurosurg Psychiatry 2010;81:547-51. 11. American Psychiatric Association Committee on Nomenclature and Statistics. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Washington DC: American Psychiatric Association; 1994. 12. 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;43:250-60. 13. Kang YW, Na DL, Hahn SH. A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J Korean Neurol Assoc 1997;15:300-8. 14. Choi SH, Na DL, Lee BH, Hahm DS, Jeong JH, Yoon SJ, et al. Estimating the validity of the Korean version of expanded clinical dementia rating (CDR) scale. J Korean Neurol Assoc 2001;19:585-91. 15. 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;15:609-15. 16. van Straaten EC, Scheltens P, Knol DL, van Buchem MA, van Dijk EJ, Hofman PA, et al. Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study. Stroke 2003;34:1907-12. 17. Bathgate D, Snowden JS, Varma A, Blackshaw A, Neary D. Behavior in frontotemporal dementia, Alzheimer s disease and vascular dementia. Acta Neurol Scand 2001;103:367-78. 18. Sultzer DL, Levin HS, Mahler ME, High WM, Cummings JL. A comparison of psychiatric symptoms in vascular dementia and Alzheimer s disease. Am J Psychiatry 1993;150:1806-12. 19. Shah A, Ellanchenny N. Suh GH. A comparative study of behavioral and psychological symptoms of dementia in patients with Alzheimer s disease and vascular dementia referred to psychogeriatric services in Korea and the U.K. Int Psychogeriatr 2005;17:207-19. 20. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: - 201 -
임상노인의학회지제 13 권제 4 호 2012 findings from the Cache County Study on memory in aging. Am J Psychiatry 2000;157:708-14. 21. Thompson C, Brodaty H, Trollor J, Sachdev P. Behavioral and psychological symptoms associated with dementia subtype and severity. Int Psychogeriatr 2010;22:300-5. 22. Caputo M, Monastero R, Mariani E, Santucci A, Mangialasche F, Camarda R, et al. Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types. Acta Psychiatr Scand 2008;117:455-64. 23. Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 2006;16:916-28. 24. Alexopoulos GS. The vascular depression hypothesis: 10 years later. Biol Psychiatry 2006;60:1304-5. 25. Krishnan KR, Taylor WD, McQuoid DR, MacFall JR, Payne ME, Provenzale JM, et al. Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression. Biol Psychiatry 2004;55:390-7. 26. Hackett ML, Yapa C, Parag V, Anderson CS. Frequency of depression after stroke: a systematic review of observational studies. Stroke 2005;36:1330-40. = 국문요약 = 연구배경 : 치매환자에서행동심리적증상은매우흔하다. 알츠하이머병과혈관성치매에서행동심리적증상의차이에대한여러보고가있다. 그러나대혈관혈관성치매와소혈관혈관성치매의행동심리적증상의차이에대한연구는매우드물다. 이에저자들은대혈관혈관성치매와소혈관혈관성치매의행동심리적증상에서어떤차이가있는지를알아보고자하였다. 방법 : 총 77명의혈관성치매환자를뇌자기공명영상소견에따라대혈관혈관성치매와소혈관혈관성치매로나누어 K-NPI를이용해행동심리학적증상을분석하였다. 결과 : 행동심리학적증상은혈관성치매환자의 73% 에서나타났다. 양군모두에서무감동 / 무관심이가장흔했고, 우울 / 낙담, 불안의순이었다. 소혈관혈관성치매에서대혈관혈관성치매보다초조 / 공격성이더흔하고심하게나타났다 (P=0.017). 결론 : 행동심리학적증상은혈관성치매에서흔히나타나며, 대혈관혈관성치매와소혈관혈관성치매에서다른양상을보였다. 초조 / 공격성이소혈관혈관성치매에서더많았다. 중심단어 : 행동심리적증상, 혈관성치매, 무감동, 초조 - 202 -