Dementia and Neurocognitive Disorders 2012; 11: 104-110 ORIGINAL ARTICLE 파킨슨병에서인지기능에따른행동심리증상 한임태 하충건 홍창기 최준용안종현 박정진 유나영 윤병남최성혜 인하대학교의과대학신경과학교실 Behavioral and Psychological Symptoms in Patients with Parkinson s Disease According to Cognitive Function Im-Tae Han, M.D., Choong Kun Ha, M.D., Chang-Gi Hong, M.D., Jun Yong Choi, M.D., Jong-Hyun Ahn, M.D., Jeong Jin Park, M.D., Na Young Ryoo, M.D., Byung-Nam Yoon, M.D., Seong Hye Choi, M.D. Department of Neurology, Inha University School of Medicine, Incheon, Korea Received: June 26, 2012 Revision received: August 7, 2012 Accepted: August 7, 2012 Address for correspondence Seong Hye Choi, M.D. Department of Neurology, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, Incheon 400-711, Korea Tel: +82-32-890-3659 Fax: +82-32-890-3864 E-mail: seonghye@inha.ac.kr Background: Parkinson s disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms such as cognitive impairment and neuropsychiatric symptoms. The aim of this study was to investigate the spectrum of neuropsychiatric symptoms in PD according to cognitive function. Methods: One hundred twenty seven patients with PD were consecutively recruited. They had undergone an intensive interview with a neurologist and the Seoul Neuropsychological Screening Battery-dementia version, and were divided into three groups: 27 patients in PD with normal cognition (PDNC), 57 in PD with mild cognitive impairment (PDMCI), and 43 in PD with Dementia (PDD). Forty five healthy controls without memory complaints were also recruited. The caregivers of all participants administered the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI). Results: There were significant differences in the CGA-NPI score (22.8± 20.9 vs. 6.4± 10.1 vs. 1.7± 3.9 vs. 1.0± 1.6, p < 0.001), and the prevalence of neuropsychiatric symptoms (100% vs. 64.9% vs. 37.0% vs. 44.4%, p < 0.001) among PDD, PDMCI, PDNC and control groups. Depression was the most common symptom (43.3%), followed by anxiety (31.5%), apathy (26.8%), and night-time behavior (26.8%) in all PD patients. Delusion, hallucination, and aberrant motor behavior were observed frequently in PDD, but were rare in PDMCI. Conclusions: Depression was the most common neuropsychiatric symptom in PD. The presence of delusion, hallucination, or aberrant motor behavior may suggest PDD. The neuropsychiatric symptoms were not prevalent in PD with normal cognition. 본연구는인하대학교와보건복지부보건의료연구개발사업의지원에의하여이루어진것임 ( 과제고유번호 : A102065). Key Words: Parkinson s disease, Cognitive impairment, Neuropsychiatric symptoms 서론파킨슨병은알츠하이머병다음으로흔한신경퇴행질환으로 65 세이상노인에서 1.8% 의유병률을보인다 [1]. 파킨슨병환자들에서경도인지장애의유병률은 19-40% 이다 [2]. 또한파킨슨병환자의약 30% 에서치매로진행하는것으로알려져있다 [3, 4]. 파킨슨병에서관찰되는치매는나이가많을수록, 그리고파킨슨병이진행할수록발생할가능성이커진다. 파킨슨병은안정떨림, 경직, 운동완만및자세불안정성등의운동증상이주된증상이지만, 우울, 불안, 치매, 정신병적증상, 자율신경계이상, 수면장애등과같은다양한비운동증상을동반한다 [5, 6]. 우울증상은파킨슨병에서가장흔하게관찰되는비운동증상들중의한가지로, 대략 35% 의파킨슨병환자들에서관찰된다 [7]. 파킨 슨병에서는우울증상외에도불안, 무감동 (apathy), 수면장애 (nighttime behavior), 환각 (hallucination) 등의행동심리증상 (behavioral and psychological symptoms) 들이흔하게관찰된다. 일반적으로행동심리증상은치매를동반한파킨슨병환자들에서더흔하다 [8]. 537명의파킨슨병치매환자들을조사한자료에의하면 89% 의환자들에서한가지이상의행동심리증상이관찰되었고 64% 의환자들에서 NPI 세부항목점수가 4점이상으로높은항목이한가지이상관찰되었다 [8]. 가장흔한증상은우울증상 (58%), 무감동 (54%), 불안증상 (49%), 환각 (44%) 이었고, 치매가심할수록, 파킨슨병이진행할수록행동심리증상도더다양하고심하게관찰되었다. 치매가없는파킨슨병환자들을대상으로한연구에서는 77% 환자들에서한가지이상의행동심리증상이관찰되었고, 우울증상 (40%), 무감동 (39%), 불안증상 (17%), 수면장애 (33%), 환각 (10%) 이흔하게관찰되었다 [9]. 104
파킨슨병에서인지기능에따른행동심리증상 105 또파킨슨병으로처음진단받고아직파킨슨병치료제를복용하지않은환자들을대상으로행동심리증상을조사한연구에서는 56% 의환자들에서한가지이상의행동심리증상이관찰되었고, 우울증상 (37%), 무감동 (27%), 수면장애 (18%) 등이흔하게관찰되었다 [10]. 이러한행동심리증상은파킨슨병환자와가족들에게고통이되며삶의질을저하시키므로적극적으로조기에진단하고치료가필요하다 [9, 11]. 기존의연구들에서는파킨슨병치매와치매가없는파킨슨병으로나누어서행동심리증상을조사하였지만, 경도인지장애를동반한파킨슨병과정상인지기능을가진파킨슨병으로나누어행동심리증상의차이를조사하지는않았다. 본연구에서는파킨슨병치매, 경도인지장애를동반한파킨슨병, 정상인지기능의파킨슨병으로구분하여인지기능의중등도에따른행동심리증상의차이를조사하였다. 대상과방법 2008년 1월부터 2011년 12월까지 OO병원신경과에서, United Kingdom Parkinson s disease Society Brain Bank 의특발성파킨슨병 (idiopathic Parkinson s disease) 진단기준에따라특발성파킨슨병으로진단되었고 [12] 자세한신경심리검사와 Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) [13] 를시행한 127 명의환자들을연구대상으로하였다. 보호자및환자에게자세한문진과신경심리검사를시행하여, 43명은파킨슨병치매 (dementia associated with Parkinson s disease, PDD) 로진단하였고 57명은경도인지장애를동반한파킨슨병 (Parkinson s disease with mild cognitive impairment, PDMCI), 27명은정상인지기능의파킨슨병 (Parkinson s disease with normal cognition, PDNC) 으로진단하였다. PDD군에는 Movement Disorder Society Task Force 가제시한파킨슨병치매 (probable PDD) 의진단기준중에서유력한파킨슨병치매 (probable PDD) 에부합하는환자들만포함하였다 [14]. PDMCI 의진단은 International Working Group on MCI 의진단기준 [15] 에따라정상인지기능도치매도아니면서인지기능의감퇴를환자나보호자가호소하고일상생활능력이유지되어있고, 서울신경심리검사 (Seoul Neuropsychological Screening Battery) 의 Seoul Verbal Learning Test 의지연회상, Rey Osterrieth Complex figure의보고그리기와지연회상, 단축형보스톤이름대기검사, 동물이름대기, 음소적유창성검사, 스트룹검사의색깔읽기중의한가지이상의점수가비슷한나이와학력의정상인평균에서표준편차의 1.5배를뺀값보다낮은경우에진단하였다 [16]. PDNC는위에제시한서울신경심리검사의소검사들의점수가비슷한나이와학력의정상인평균에서표준편차의 1.5배를뺀값의 이상인경우로정의하였다. 뇌자기공명영상에서특발성파킨슨병이외의수두증, 혈관성파킨슨증후군등의다른원인질환이관찰되는경우는제외하였다. 임상병리검사에서인지기능에저하를가져올수있는갑상샘기능이상이나매독, 비타민 B12나엽산결핍, 만성신부전이나간부전등의대사성원인질환, 완치판정을받지않은악성종양이관찰되거나, 약물로인한파킨슨증후군과비특이성파킨슨증후군 (atypical parkinsonism), 최근 10년이내에약물중독이나매일 3잔이상의술을마시는알코올중독의기왕력이나정신병이있거나, 뇌염, 1시간이상의식을잃은뇌외상, 외상성뇌출혈, 뇌종양, 뇌졸중의기왕력이있거나, 환자의상태에대한정보를충분히알려줄보호자가없는경우는제외하였다. 모든환자들에게전반적인인지기능의측정을위해 Korean Mini- Mental Status Examination (K-MMSE) [17], Clinical Dementia Rating (CDR) scale [18] 을시행하였고자세한인지기능의평가를위해서울신경심리검사를진행하였다. 보호자에게환자에대한 Seoul Instrumental Activities of Daily Living (SIADL) [19] 과 CGA-NPI 를작성하도록하였다. 신경과에내원한환자들의보호자들중에서기억장애를호소하지않고신경계질환이나정신병의기왕력이없고 K-MMSE 점수가나이와학력을고려할때정상규준에포함되는 45명을정상대조군으로하였다. 1. 통계분석연구대상군간의나이, 학력, 파킨슨병의유병기간, 발병연령, Hoehn and Yahr (H & Y) 단계, K-MMSE 점수, CGA-NPI 총점과세부항목들의점수의차이는 ANOVA 검정으로조사하였고사후분석은 Turkey 방법으로조사하였다. 연구대상군간의성별과정보제공자와의관계및동거여부, CGA-NPI 상의이상행동들의유병률은 Chi-square 검정으로비교하였다. 각군간의유병률은 Permutation test를시행하여비교하였다. 남녀간의 CGA-NPI 점수의차이, 파킨슨병약물치료를받고있는환자들과받고있지않은환자들간의 CGA-NPI 점수의차이는 Student t-test 로조사하였다. 나이, 학력, 발병연령, K-MMSE, H & Y 단계와 CGA-NPI 점수와의상관관계는 Spearman correlation coefficient 로조사하였다. 나이, 성별, K-MMSE, H & Y 단계와 CGA-NPI 와의관련성을단계별 (stepwise) 다중선형회귀분석으로조사하였다. CGA-NPI 의세부항목의점수가 4점이상인경우를임상적으로유의한 (clinically significant) 이상으로정의하였다 [20]. 연구결과의분석은통계처리프로그램인 SPSS version 18.0 을이용하였으며, Permutation test는 SAS 9.3을이용하였다. 통계학적유의수준은 p < 0.05인경우의미있는것으로판정하였다.
106 한임태 하충건 홍창기외 6 인 결과 1. 연구대상의인구학적및임상적특성 127 명의파킨슨병환자들의평균나이는 70.2± 9.3 세이었고, 남자는 48명, 여자는 79명이었다. 평균학력은 5.9 ± 4.7년이고, 파킨슨병의평균유병기간은 39.2 ± 45.5개월이었고, K-MMSE 의평균점수는 22.1± 5.6점이었다. 전체 127명의파킨슨병환자중유력한 PDD로진단된환자는 43명 (33.9%) 이고 PDMCI 는 57명 (44.8%), PDNC 군은 27명 (21.3%) 이었다. PDD, PDMCI, PDNC, 정상대조군간의나이, 성별, 학력, 발병연령, 유병기간, H & Y단계, K-MMSE 점수, CGA-NPI 의정보제공자와의관계및동거여부는 Table 1에제시하였다. 나이, 성별, 학력, CGA-NPI 정보제공자와의관계및동거여부, 발병연령은연구대상군간에유의한차이가관찰되지않았다. 파킨슨병의유병기간은 PDD군에서 PDMCI군과 PDNC군에비하여유의하게길었다 (68.1± 57.4 개월 vs. 25.3 ± 29.2개월 vs. 22.6 ± 27.6 개월, p< 0.001). H & Y 단계는 PDD군이가장높았고그다음으로 PDMCI군이높았고 PDNC 군이가장낮았다 (2.8± 0.9 vs. 1.8± 0.6 vs. 1.3± 0.7, p < 0.001). K-MMSE 점수는 PDD군에서 PDMCI 군과 PDNC 군및정상대조군보다유의하게낮았다 (19.8± 6.0 vs. 22.7± 5.5 vs. 24.7± 3.7 vs. 26.2 ± 2.9, p< 0.001). PDMCI 군은정상대조군보다유의하게 K-MMSE 점수가낮았고, PDNC군보다도낮았으나통계적유의성은관찰되지않았다. 2. CGA-NPI 점수와임상적특성간의관련성 CGA-NPI 점수는 PDD 군에서 PDMCI 군과 PDNC 군및정상대조군보다유의하게높았다 (22.8 ± 20.9 vs. 6.4 ± 10.1 vs. 1.7± 3.9 vs. 1.0 ± 1.6, p< 0.001). PDMCI 군은 PDNC 군과정상대조군보다 CGA-NPI 점 수가높았으나통계적유의성은관찰되지않았다. PDNC군과정상대조군의 CGA-NPI 점수는유사하였다. PDD군에서 12명, PDMCI 군에서 39명, PDNC군에서 18명이파킨슨병약물치료를받고있지않았다. PDD 군 (24.9± 22.2 vs. 17.4 ±16.6, p = 0.30) 과 PDMCI 군 (8.9± 14.9 vs. 5.3 ± 6.9, p= 0.21) 및 PDNC군 (2.8± 5.2 vs. 1.2 ± 3.1, p= 0.33) 각각에서파킨슨병약물치료를받고있는환자들과파킨슨병약물치료를받고있지않은환자들간에 CGA-NPI 점수의유의한차이는관찰되지않았다. 파킨슨병환자들에서남녀간에 CGA-NPI 점수의차이는없었다 (11.2 ± 17.4 vs. 10.9 ± 15.9, p= 0.92). CGA-NPI 총점과조사당시나이, 학력및발병연령간에는유의한상관관계가관찰되지않았으나, K-MMSE 와는유의한음의상관관계가관찰되었고 (r = -0.22, p= 0.01), H & Y 단계와도유의한양의상관관계가관찰되었다 (r = 0.59, p< 0.001). 다행감을제외한모든세부항목들에서 H & Y 단계와유의한상관관계가관찰되었다 (r = 0.20-0.45, p < 0.05). 단계별다중선형회귀분석에서나이, 성별, K-MMSE 점수는 CGA-NPI 점수와관련성이없었으나 H & Y 단계는유의한관련성이관찰되었다 (R 2 = 0.28, β = 9.26, 95% confidence interval of β = 6.62-11.90, p < 0.001). 3. 인지기능에따른 CGA-NPI 세부항목들의점수및유병률의비교네군간의 CGA-NPI 세부항목들의점수는 Table 2에제시하였다. CGA-NPI 세부항목들의점수는빈도와심한정도를곱한점수를비교하였는데, 다행감 (euphoria) 과탈억제 (disinhibition) 는네군간에서모두점수가낮았고통계적으로유의한차이도관찰되지않았다. 이두세부항목을제외한모든세부항목들에서 PDD군에서 PDNC 군과정상대조군보다점수가유의하게높았다. 망상 (delusion), 환각, 초조 (agitation), 무감동, 과민 (irritability), 이상운동행동 (aberrant motor behavior), 수면장애에서는 PDMCI 군보다 PDD군에서유의하게점수가높았으나, 우울, 불안, 식이변화 (eating change) 에서는 Table 1. Clinical characteristics of the patients with dementia associated with Parkinson s disease (PPD), those with PD with mild cognitive impairment (PDMCI), those with PD with normal cognition (PDNC), and normal controls PDD (n=43) PDMCI (n=57) PDNC (n=27) Control (n=45) p value Age (yr) 72.3± 7.3 69.3± 9.6 68.7±11.0 68.2± 7.5 0.14 Men : women 21 : 22 15 : 42 12 : 15 15 : 30 0.10 Education (yr) 4.9± 4.3 5.9± 4.9 7.6±4.7 6.9± 5.3 0.09 Informants Spouse : son/daughter : relative 19 : 23: 1 22 : 31 : 4 11 : 15 : 1 23 : 22 : 0 0.55 Living with the patient (%) 25 (58.1%) 29 (50.9%) 14 (51.9%) 33 (73.3%) 0.11 Age of onset (yr) 66.3± 9.1 67.0± 9.8 66.6±10.5 0.95 Duration of disease (months) 67.8 ± 52.9, 25.3 ± 28.9 24.1 ± 27.4 < 0.001 Hoehn and Yahr staging 2.8 ± 0.9, 1.8 ± 0.6, 1.3 ± 0.7, < 0.001 K-MMSE 19.8 ± 6.0,, 22.7 ± 5.5, 24.7 ± 3.7 26.2 ± 2.9, < 0.001 p< 0.05 vs. PDD; p< 0.05 vs. PDMCI; p< 0.05 vs. PDNC; p< 0.05 vs. Control. K-MMSE, Korean Mini-Mental State Examination.
파킨슨병에서인지기능에따른행동심리증상 107 Table 2. Subscale scores of CGA-NPI in patients with PDD, PDMCI, and PDNC, and controls Behavioral domains Control (n=45) PDD (n=43) PDMCI (n=57) PDNC (n=27) p value Delusions 0.0 ± 0.0 2.4 ± 3.7,, 0.1 ± 0.8 0.0 ± 0.0 < 0.001 Hallucinations 0.0 ± 0.0 2.9 ± 4.1,, 0.2 ± 0.9 0.0 ± 0.0 < 0.001 Agitation 0.0 ± 0.0 1.0 ± 1.8,, 0.3 ± 0.9 0.0 ± 0.2 0.002 Depression 0.3 ± 0.6 2.1 ± 3.3, 1.3 ± 2.4 0.4 ± 0.8 0.03 Anxiety 0.4 ± 1.0 2.0 ± 3.1, 1.0 ± 2.3 0.2 ± 0.5 0.009 Euphoria 0.0 ±0.0 0.2 ± 0.8 0.0 ±0.0 0.0 ± 0.0 0.15 Apathy 0.1 ± 0.3 2.8 ± 4.2,, 0.8 ± 2.1 0.3 ± 1.2 < 0.001 Disinhibition 0.0 ± 0.0 0.7 ± 2.2 0.3 ±1.3 0.2 ± 0.7 0.32 Irritability 0.0 ± 0.3 1.4 ± 2.7,, 0.3 ± 0.8 0.3 ± 1.2 0.003 Aberrant motor behavior 0.0 ± 0.0 1.6 ± 3.0,, 0.1 ± 0.8 0.0 ± 0.0 < 0.001 Night-time behavior 0.2 ± 0.7 3.4 ± 4.2,, 0.8 ± 2.2 0.2 ± 1.2 < 0.001 Eating change 0.1 ± 0.5 2.4 ± 4.2, 1.4 ± 3.2 0.2 ± 0.6 0.02 Total CGA-NPI score 1.0 ± 1.6 22.8 ± 20.9,, 6.4 ± 10.1 1.7 ± 3.9 < 0.001 p< 0.05 vs. PDD; p< 0.05 vs. PDMCI; p< 0.05 vs. PDNC; p< 0.05 vs. Control. CGA-NPI, Caregiver-Administered Neuropsychiatric Inventory; PDD, Dementia associated with Parkinson s disease; PDMCI, Parkinson s disease with mild cognitive impairment; PDNC, Parkinson s disease with normal cognition. 두군간에유의한차이가관찰되지않았다. PDMCI 군에서정상대조군과 PDNC군보다우울, 불안, 무감동, 수면장애, 식이변화에서점수가높았으나통계적유의성은관찰되지않았다 (Table 2). 네군간의행동심리증상의유병률을 Table 3에제시하였다. 전체파킨슨병환자들의 70.9% 에서한가지이상의행동심리증상이관찰되었고, 가장흔하게관찰되는행동심리증상은우울증상으로 43.3% 의환자들에서관찰되었다. 그다음으로흔하게관찰되는행동심리증상은불안증상 (31.5%) 이었고, 무감동 (26.8%) 과수면장애 (26.8%) 가그다음으로흔하게관찰되었다. 가장드물게관찰되는행동심리증상은다행감 (1.6%) 이었고, 이상운동행동 (11.0%) 과탈억제 (12.6%) 가그뒤를이었다. 다행감의유병률은 PDD, PDMCI, PDNC, 정상대조군간에서도유의한차이가관찰되지않았고, 이상운동증상은 PDMCI, PDNC, 정상대조군에서는거의관찰되지않았으나 PDD군에서는빈번하게관찰되었다 (1.8% vs. 0% vs. 0% vs. 30.2%, p < 0.001). 군간비교에서는망상, 환각, 이상운동행동, 수면장애에서 PDD군이정상대조군, PDMCI, PDNC 군보다유의하게유병률이높았다. 초조, 우울, 무감동, 과민, 식이변화에서는 PDD군과정상대조군간에만유병률에차이가있었고, 불안에서는 PDD군과정상대조군및 PDNC 군간의유병률에유의한차이가관찰되었다. 탈억제에서는군간비교에서는유의한차이가관찰되지않았다. 우울증상은네군에서모두가장빈번하게관찰되는행동심리증상이었고, 인지기능저하가진행될수록우울증상이빈번하게관찰되었다 (Fig. 1). 그러나우울증상항목점수가 4점이상으로임상적으로유의한우울증상 [8, 20] 은 PDNC와정상대조군에서는한명도관찰되지않았고, PDMCI 군과 PDD군에서는각각 12.3% 와 16.3% 로상대적으로높게관찰되었다. 대부분의행동심리증상들에서 PDNC군은정상대조군과유사한정도의유병률을보였다 (Table 3). PDMCI (%) 70 60 50 40 30 20 10 0 Delusion Hallucination Agitation Depression Anxiety Euphoria Apathy Disinhibition 군은 PDNC 군에비하여우울증상 (36.9% vs. 25.9%), 불안증상 (28.1% vs. 11.1%), 무감동 (21.1% vs. 11.1%), 수면장애 (15.8% vs. 3.7%), 식이변화 (24.6% vs. 7.4%) 에서유병률이높았다. PDD 군에서는모든환자들에 서한가지이상의행동심리증상이관찰되었다. PDD 군에서는 PDMCI 군보다모든행동심리증상들이빈번하였는데, 특히망상 (41.9% vs. 3.6%), 환각 (55.8% vs. 7.1%), 이상운동행동증상 (30.3% vs.1.8%) 이 PDMCI 군에서는 10% 미만으로드물었는데 PDD 군에서는 30% 이상으로흔하게관찰되었다 (Table 3). Control PDNC PDMCI PDD Irritability Aberrant motor behavior Night-time behavior Eating change Fig. 1. Prevalence of behavioral and psychiatric symptoms in the patients with dementia associated with Parkinson s disease (PPD), those with PD with mild cognitive impairment (PDMCI), those with PD with normal cognition (PDNC), and normal controls. Items which were significantly different among four groups (p < 0.05).
108 한임태 하충건 홍창기외 6 인 Table 3. Prevalence of behavioral and psychiatric symptoms in patients with PDD, PDMCI, and PDNC, and controls Syndrome Total PD (n = 127) Control (n = 45) PDD (n = 43) PDMCI (n = 57) PDNC (n = 27) p Any syndrome Yes ll 90 (70.9) 20 (44.4) 43 (100),, 37 (64.9) 10 (37.0) < 0.001 Mild 33 (26.0) 18 (40.0) 7 (16.3) 18 (31.6) 8 (29.6) Clinically significant 57 (44.9) 2 (4.4) 36 (83.7) 19 (33.3) 2 (7.4) Delusions Yes ll 20 (15.7) 0 (0.0) 18 (41.9),, 2 (3.6) 0 (0.0) < 0.001 Mild 8 (6.3) 0 (0.0) 7 (16.3) 1 (1.8) 0 (0.0) Clinically significant 12 (9.4) 0 (0.0) 11 (25.6) 1 (1.8) 0 (0.0) Hallucinations Yes ll 28 (22.0) 0 (0.0) 24 (55.8),, 4 (7.1) 0 (0.0) < 0.001 Mild 15 (11.8) 0 (0.0) 12 (27.9) 3 (5.3) 0 (0.0) Clinically significant 13 (10.2) 0 (0.0) 12 (27.9) 1 (1.8) 0 (0.0) Agitation Yes ll 22 (17.3) 0 (0.0) 15 (34.9) 6 (10.6) 1 (3.7) < 0.001 Mild 17 (13.4) 0 (0.0) 11 (25.6) 5 (8.8) 1 (3.7) Clinically significant 5 (3.9) 0 (0.0) 4 (9.3) 1 (1.8) 0 (0.0) Depression Yes ll 55 (43.3) 10 (22.2) 27 (62.8) 21 (36.9) 7 (25.9) 0.001 Mild 41 (32.3) 10 (22.2) 20 (46.5) 14 (24.6) 7 (25.9) Clinically significant 14 (11.0) 0 (0.0) 7 (16.3) 7 (12.3) 0 (0.0) Anxiety Yes ll 40 (31.5) 7 (15.5) 21 (48.8), 16 (28.1) 3 (11.1) 0.001 Mild 24 (18.9) 6 (13.3) 12 (27.9) 9 (15.8) 3 (11.1) Clinically significant 16 (12.6) 1 (2.2) 9 (20.9) 7 (12.3) 0 (0.0) Euphoria Yes ll 2 (1.6) 0 (0.0) 2 (4.6) 0 (0.0) 0 (0.0) 0.11 Mild 1 (0.8) 0 (0.0) 1 (2.3) 0 (0.0) 0 (0.0) Clinically significant 1 (0.8) 0 (0.0) 1 (2.3) 0 (0.0) 0 (0.0) Apathy Yes ll 34 (26.8) 3 (6.7) 19 (44.2) 12 (21.1) 3 (11.1) < 0.001 Mild 15 (11.8) 3 (6.7) 6 (14.0) 7 (12.3) 2 (7.4) Clinically significant 19 (15.0) 0 (0.0) 13 (30.2) 5 (8.8) 1 (3.7) Disinhibition Yes ll 16 (12.6) 0 (0.0) 8 (18.6) 6 (10.5) 2 (7.4) 0.03 Mild 10 (7.9) 0 (0.0) 4 (9.3) 4 (7.0) 2 (7.4) Clinically significant 6 (4.7) 0 (0.0) 4 (9.3) 2 (3.5) 0 (0.0) Irritability Yes ll 24 (18.9) 1 (2.2) 14 (32.6) 8 (14.1) 2 (7.4) 0.001 Mild 16 (12.6) 1 (2.2) 8 (18.6) 7 (12.3) 1 (3.7) Clinically significant 8 (6.3) 0 (0.0) 6 (14.0) 1 (1.8) 1 (3.7) Aberrant motor behavior Yes ll 14 (11.0) 0 (0.0) 13 (30.3),, 1 (1.8) 0 (0.0) < 0.001 Mild 6 (4.7) 0 (0.0) 6 (14.0) 0 (0.0) 0 (0.0) Clinically significant 8 (6.3) 0 (0.0) 7 (16.3) 1 (1.8) 0 (0.0) Night-time behavior Yes ll 34 (26.8) 3 (6.6) 24 (55.8),, 9 (15.8) 1 (3.7) < 0.001 Mild 12 (9.5) 2 (4.4) 8 (18.6) 4 (7.0) 0 (0.0) Clinically significant 22 (17.3) 1 (2.2) 16 (37.2) 5 (8.8) 1 (3.7) Eating change Yes ll 33 (26.0) 2 (4.4) 17 (39.6) 14 (24.6) 2 (7.4) < 0.001 Mild 15 (11.8) 2 (4.4) 6 (14.0) 7 (12.3) 2 (7.4) Clinically significant 18 (14.2) 0 (0.0) 11 (25.6) 7 (12.3) 0 (0.0) Values were presented as number (percent). p< 0.05 vs. PDD; p< 0.05 vs. PDMCI; p< 0.05 vs. PDNC; p< 0.05 vs. Control; ll Proportion with non-zero score; mild: score of a subscale of CGA-NPI, 1-3; clinically significant: score of a subscale of CGA-NPI 4. PDD, Dementia associated with Parkinson s disease; PDMCI, Parkinson s disease with mild cognitive impairment; PDNC, Parkin son s disease with normal cognition.
파킨슨병에서인지기능에따른행동심리증상 109 고찰본연구에서 70.9% 의파킨슨병환자들에서한가지이상의행동심리증상이관찰되어파킨슨병에서행동심리증상이매우흔하게나타난다는것을알수있었다. 이는기존의연구결과와유사하다 [9]. 500여명의 PDD 환자들을대상으로한연구에의하면 89% 의환자들에서한가지이상의행동심리증상이관찰되었고 64% 의환자들에서 NPI 세부항목점수가 4점이상으로높은항목이한가지이상관찰되었다 [8]. 본연구에서는모든 PDD 환자들에서한가지이상의행동심리증상이관찰되었고 83.7% 에서 CGA-NPI 세부항목점수가 4점이상으로높은항목이한가지이상관찰되었다. 본연구에서기존의 PDD 대상연구와약간의차이를보인것은기존의연구에비하여대상수가상대적으로적어서일가능성이있다. 또치료받지않은초기파킨슨병환자들을대상으로한연구에서행동심리증상이 56% 에서관찰되었는데 [10], 본연구의 PDNC군에서의유병률 (37%) 보다높고 PDMCI 군의유병률 (64.9%) 보다는낮은수치이다. 이는연구대상에 PDMCI와 PDNC군이합쳐져있었기때문으로생각할수있다. 본연구에서도 PDMCI 군과 PDNC군을합하여분석하였을때는 56% 에서한가지이상의행동심리증상이관찰되어기존의결과와유사하였다 [10]. 본연구에서도기존의연구처럼 [8] 인지장애가진행할수록행동심리증상들이정도가심하고다양하게나타나는양상을보였다. 그러나정상인지기능을보이는파킨슨병환자들을대상으로행동심리증상을분석한기존의연구는없었다. 본연구에서파킨슨병이어도정상인지기능을보이는경우에는정상대조군과행동심리증상의빈도나점수에유의한차이가없었다. 따라서파킨슨병에서행동심리증상이나타나면인지기능저하가시작되었음을시사할가능성이크다고할수있다. 그외에환자의나이나발병연령, 학력이나성별은행동심리증상과관련성이없었고, 운동증상의심한정도를나타내는 H & Y 단계가전반적인인지기능을나타내는 K-MMSE 점수를보정하고도행동심리증상과유의한관련성을보였다. 즉 H & Y 단계가높을수록행동심리증상점수도높았다. 이는기존의연구와유사하다 [8]. 파킨슨병환자들에서가장흔하게관찰되는행동심리증상은우울증상 (43.3%) 이었다. 그다음으로흔하게관찰되는행동심리증상은불안증상 (31.5%), 무감동 (26.8%), 수면장애 (26.8%) 순이었으며이는기존의연구결과와도유사하였다 [7]. 다행감 (1.6%), 탈억제 (12.6%), 이상운동행동증상 (11%) 은드물게관찰되었다. 다행감, 탈억제의유병률및항목점수는 PDD, PDMCI, PDNC 및정상대조군간에유의한차이가관찰되지않았다. 우울증상항목점수가 4점이상으로임상적으로유의한우울증상은 PDD군 (16.3%) 과 PDMCI 군 (12.3%) 에서는높은빈도로관찰되었으나 PDNC와정상대조군에서는한 명도관찰되지않았다. 이를통하여파킨슨병환자에서임상적으로유의한우울증상이있으면인지장애가있을가능성이높음을알수있다. PDD군에서는 PDMCI 군보다모든행동심리증상들의유병률이높았는데, 특히망상 (41.9% vs. 3.6%), 환각 (55.8% vs. 7.0), 이상운동행동증상 (30.2% vs.1.8%) 이 PDMCI군에서는 10% 미만으로드물었는데 PDD군에서는 30% 이상으로유병률이높았다. 따라서파킨슨병환자에서망상, 환각, 또는이상운동행동이나타나면파킨슨병치매를의심할수있다. PDD군에서는망상보다환각의유병률이높았는데알츠하이머병환자들에서환각보다망상이더빈번히관찰되는것과는대비된다 [21]. 본연구의한계점으로는연구에참여한대상환자의숫자가적었고, 파킨슨병에서흔하게관찰되는강박증상 (obsessive-compulsive symptoms) 을조사하지않았고, 파킨슨병의진단이조직검사를통한확진이아니라임상적으로만이루어졌다는것이다. 그외에파킨슨병치료제를복용하고있는환자들도연구에다수가포함되었다는한계점이있다. 파킨슨병치료제는행동증상의발현에영향을미친다 [22]. 특별히도파민작용성약물은환시의발현과관련성을가진다 [22]. 그러나본연구에서파킨슨병약물치료를받고있지않은환자들과파킨슨병약물치료를받는환자들간에 CGA-NPI 점수에유의한차이가관찰되지않아, 본연구에서관찰된인지기능에따른행동심리증상의차이가파킨슨병치료제로인할가능성은크지않다고생각된다. 결론적으로, 본연구에서파킨슨병에서행동심리증상들이높은빈도로관찰되고우울증상이가장흔하게나타난다는것을알수있었다. 또한행동심리증상이나타나면인지기능저하가동반되어있을가능성이크며, 인지기능저하가심하거나운동증상이심할수록다양한행동심리증상들이심하게나타났다. 이번결과를바탕으로파킨슨병환자에게망상, 환각, 이상운동행동이나타날때는파킨슨병치매로의진행을의심해볼것을제안하는바이다. 참고문헌 1. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al. Prevalence of Parkinson s disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000; 54(11 Suppl 5): S21-3. 2. Aarsland D, Bronnick K, Williams-Gray C, Weintraub D, Marder K, Kulisevsky J, et al. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 2010; 75: 1062-9. 3. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Preva-
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