ORIGINAL ARTICLE Korean J Clin Lab Sci. 2019;51(1):105-113 https://doi.org/10.15324/kjcls.2019.51.1.105 pissn 1738-3544 eissn 2288-1662 Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 105 Study on Correlation between Cognitive Impairment and Geriatric Depression or Geriatric Stress Dae Jin Kim 1,, Soo-Young Cho 2,, Jeong Su Choi 3, Min Woo Lee 4, Eun-Kyung Cho 5, Se-hee Kang 2,6, Suhng Wook Kim 6 1 Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea 2 Department of Neurology, Seoul National University Hospital, Seoul, Korea 3 Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea 4 Institute of Health Science, College of Health Science, Korea University, Seoul, Korea 5 Department of Laboratory Medicine, Graduate School of Medicine, Kangwon National University, Chuncheon, Korea 6 Department of Health and Safety Convergence Science, Graduate School, Korea University, Seoul, Korea 인지기능과노인성우울, 노인성스트레스의연관성에대한연구 김대진 1,, 조수영 2,, 최정수 3, 이민우 4, 조은경 5, 강세희 2,6, 김성욱 6 1 부산대학교양산병원신경과, 2 서울대학교병원신경과, 3 고려대학교대학원의생명융합과학과, 4 고려대학교보건과학대학보건과학연구소, 5 강원대학교의학과대학원진단검사의학전공, 6 고려대학교대학원보건안전융합과학과 This study examined the effects of geriatric depression and geriatric stress on cognitive impairment. In particular, the dementia groups were divided into Alzheimer s disease and vascular dementia. A normal group was used as the control group. For each group, the geriatric depression using the geriatric depression scale (GDS) and geriatric stress using the geriatric stress scale (GSS) was compared with the regression and correlation results of cognitive impairment. Statistical tests, such as descriptive statistics, Kruskall-Wallis, correlation analysis, and multiple regression analysis, were performed. For the Alzheimer s group, the GDS and GSS correlated with the cognitive impairment, but only the GDS showed a cause-and-effect relationship with cognitive impairment. In particular, the male group with Alzheimer s disease showed clear confirmation. In addition, geriatric stress was found to be associated with geriatric depression. In conclusion, geriatric depression affects the cognitive impairment directly and geriatric stress affects the cognitive ability indirectly through geriatric depression. In this study, the Alzheimer s disease, vascular dementia, and control groups had a small sample size. Therefore, the external validity in future studies can be increased using a larger sample size for each group. Key words: Alzheimer s disease, Cognitive impairment, Geriatric depression, Geriatric stress, Vascular dementia These authors contributed equally to this work as the first co-authors. Corresponding author: Suhng Wook Kim Department of Health and Safety Convergence Science, Graduate School, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea Tel: 82-2-3290-5686 Fax: 82-2-940-2829 E-mail: swkimkorea@korea.ac.kr ORCID: https://orcid.org/0000-0001-5522-0447 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2019 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: January 4, 2019 Revised: February 7, 2019 Accepted: February 8, 2019 서론치매는각종소인으로인해뇌기능이손상되면서기억력, 언어능력, 시공간능력, 집중력, 수행능력등의인지기능장애와함께이상행동과불안, 초조, 우울등의심리적증상및일상생활 능력을손상받는질환이다 [1]. 치매의하위유형은정확한원인은밝혀지지않았지만타우단백질, 아밀로이드베타등이대뇌에축적되면서뇌신경세포가지속적인손상을입는퇴행성신경질환인알츠하이머성치매 (Alzheimer s disease, AD) 로전체치매의절반이상을차지하고 [2, 3], 다양한뇌혈관질환으로
106 Dae Jin Kim, et al. A Correlation between Cognitive Impairment and GDS or GSS 인해인지장애가생긴경우인혈관성치매 (vascular dementia, VD) 는약 20 30% 의비중을차지하며다발경색치매, 전략적뇌경색치매, 피질하 VD 등으로구분된다 [4]. 치매의증상은초, 중, 말기로구분하며중기이후관찰되는행동및심리증상장애 (behavioral and psychological symptoms of dementia, BPSD) 는치매를악화시키고보호자들의삶의질에큰영향을주며치매환자가보호시설에수용되는가장큰이유로환자돌봄의비용증가를야기시키므로관심을가져야한다 [5]. BPSD의증상으로는우울증, 불안등의심리증상과공격성, 배회, 부적절한식사등의행동증상이있다 [6]. 이중우울증은 AD의 40 50% 에서관찰되며 [7], 우울증이 AD의전조증상이라추정하기도한다 [8]. 또한 VD에서는 AD보다더욱빈번하고심한수준의우울증이관찰된다고보고되었다 [9]. 우울증은정상노인 40% 에서나타나는노년기대표질병이며, 우울증노인은인지기능저하가관찰된다는연구결과가보고되었고 [10], 치매환자는정상노인보다정서적상태및인지기능등전반적으로더우울한것으로알려져있다 [11]. 하지만지금까지의연구에서는치매환자의인지장애와우울, 불안과같은정서장애간연관에대한조사만있었고 [12, 13], 초, 중년층과다른노년기의삶에서발생된내ㆍ외적인환경요소의변화로인한생활패턴및정서의변화가가져온스트레스에대한영향이반영된연구결과는없었다. 우리의삶은다양한인과관계에의해형성되며, 우울이란감정도삶의방식의변화, 가족문제, 경제적상황, 신체적건강상태, 소외문제, 주변환경등의여러스트레스요소에대해민감한영향을받을수있고, 이러한다양한스트레스로인한감정적이나생리학적변화가기억력의저하와인과관계가있는것으로보고되었다 [14]. 이처럼우울과함께스트레스도기억력저하를기반으로다양한정서장애및인지적수행능력들을악화시키는요인으로가정할수있다. 따라서본연구에서는정상노인과치매환자를대상으로노인성우울뿐만아니라노인성스트레스가인지기능에미치는 영향을알아보고, 서로연관성을확인하고자하였다. 재료및방법 1. 대상이번연구는 2012년 1월부터 2016년 8월까지서울대학교병원신경과를방문한환자중인지장애와관련된신경과적질환을제외한다른내과적, 신경과적질환을갖지않는 60대부터 90대의노년층을대상으로하였다. 기억장애를포함한인지장애와노인성우울, 노인성스트레스를호소하는환자를대상으로신경심리검사를통해인지적요소를평가하고임상소견, 뇌영상촬영검사, 혈액학적검사등으로인지장애유발원인을밝혀내고이를바탕으로하여 AD 는 Diagnostic and statistical manual of mental disorders, 4 th edition (DSM-IV) 과 National institute of neurological and communicative disorders and stroke and the Alzheimer s disease and related disorders associations (NINCDS ADRDA) 의기준에의해진단하였고, VD는 National institute of neurological disorders and stroke and the association internationale pour Ia Recherché et l Ensignement en Neurosciences (NINDS AIREN) criteria의기준에의해진단하였으며 [15], 각유형의임상적인특징은 Table 1에설명하였다. 연구대상자는전체 240명이모집되었고한국형간이정신상태검사 (Korean version of mini-mental state exam, K-MMSE) 평가를통해정상군 80명, 치매군 160명으로분류하였다. 또한치매군 160명은앞선진단기준에따라 AD군 80명 VD군 80명으로재분류하였다. 인구통계학적인기준으로남자는 113명 (47.1%), 여자는 127명 (52.9%) 이었고, 평균연령은 75.4±7.9세로 70대 (102명) 가가장많고 90대 (11명) 가가장적었다. 또한평균학력은고등학교수준이었으며초등학교졸업 (66명) 이가장많고중학교졸업 (32명) 이가장적었다 (Table 2). 본연구는서울대학병원의학윤리심의위원회의승인하에 Table 1. The clinical features of Alzheimer s disease and vascular dementia Alzheimer's disease Vascular dementia Incidence rate 80% of dementia 10% of dementia Cause Loss of synapses, synaptic dysfunction, mitochondrial structural and functional Block or reduce blood flow to the brain, cerebrovascular inadequacy abnormalities, inflammatory responses Risk factors ApeE Hypertension Neuroimaging Hippocampal atrophy Multiple infarction, white matter lesions Progression Slow progression Gradual progression or sudden (following stroke) Cardinal symptom Memory loss, depression, anxiety, delusions, executive dysfunction Brain dysfunction of stroke lesions, depression, mild impairment
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 107 Table 2. The general characteristics of study participants Characteristics Classifications Participants (%) Total (N=240) AD group (N=80) VD group (N=80) Normal (N=80) Gender Male 113 (47.1) 34 (42.5) 40 (50.0) 39 (48.8) Female 127 (52.9) 46 (57.5) 40 (50.0) 41 (51.3) Generation Sixty 50 (20.8) 14 (17.5) 20 (25.0) 16 (20.0) Seventy 102 (42.5) 21 (26.3) 21 (26.3) 60 (75.0) Eighty 77 (32.1) 37 (46.3) 37 (46.3) 3 (3.8) Ninety 11 (4.6) 8 (10.0) 2 (2.5) 1 (1.3) Mean±SD* 75.4±7.9 78.1±8.6 75.9±7.7 72.2±6.2 Educational background Un-education 38 (15.8) 18 (22.5) 15 (18.8) 5 (6.3) Elementary 66 (27.5) 21 (26.3) 23 (28.8) 22 (27.5) Middle 32 (13.3) 11 (13.8) 11 (13.8) 10 (12.5) High 51 (21.3) 13 (16.3) 22 (27.5) 16 (20.0) University 53 (22.1) 17 (21.3) 9 (11.3) 27 (33.8) Mean±SD 3.1±1.4 2.9±1.5 2.8±1.3 3.5±1.4 *Average age for participants. Coding on educational background: Uneducation=0, Elementary=1, Middle=2, High=3, University=4. Abbreviations: AD, Alzheimer s disease; VD, Vascular dementia. 진행되었다. 2. 인지적요소측정신경심리검사를통해기억력, 주의집중력, 언어기능시공간구성능력, 계산능력, 이마엽성기능등대뇌인지영역의전반적인인지기능이설문지를통해평가되었다 [16]. 1) 한국형간이정신상태검사 (K-MMSE) Folestein 이제작한간이정신상태검사를 [17] 한국실정에맞게번안한것으로인지장애를진단하는인지기능측정검사도구로많이사용되며 [18], 시간지남력, 장소지남력, 기억등록과회상, 주의집중및계산능력, 언어능력, 시공간구성능력을평가하게된다. 신뢰도있는검사를위해환자의학력, 나이, 성별등에따라점수의평가기준을달리적용하여질적인평가를하였다 [19]. 본연구에서는정상노인을 25점이상, 치매노인을 25점미만으로구분하였다 [20]. 3) 이마엽기능검사 (frontal assessment battery, FAB) K-MMSE에서평가하기어려운이마엽성기능을세분화한것으로 [23, 24] 추상적개념화, 정신적유연성, 계획, 방해에대한민감도, 억제조절, 환경에관한자율성등 6가지영역으로범주화하여평가할수있다. FAB 17점이상은정상, 16점이하는이마엽성기능장애, 12점이하는이마-관자엽치매로추정할수있다. 4) 한국형도구적일상생활능력평가 (Korean instrumental activities of daily life, K-IADL) 시장보기, 교통수단이용, 돈관리, 기구사용및집안일하기, 음식준비, 전화사용, 취미생활, 약복용, 집안수리등으로평가항목을나누어인지장애가일상생활에미치는영향을알아보기위한설문형검사로보호자를대상으로한다. 0.0 3.0점으로점수화되며 0.43점을기준으로미만이면정상, 이상이면그정도에따라인지장애가일상생활에미치는것으로평가한다 [25]. 2) 치매임상평가척도 (clinical dementia rating, CDR) 기억력, 지남력, 판단력과문제해결, 사회활동, 집안생활과취미, 위생및몸치장의 6가지영역을범주화하고평가하여치매의심각한정도를평가할수있다 [21]. 각영역에따라 CDR 0, 0.5, 1, 2, 3, 4, 5점으로점수화하여전체치매임상평가척도 (global CDR) 로나타낸다. CDR 0점은정상, 0.5점은경도인지장애또는초기치매의상태, 1점이상은치매, 3점이상은중증의치매로분류하였다 [22]. 5) 노인우울척도 (geriatric depression scale, GDS) 총 30개의문항으로 0 17 점이하는정상, 18 20 점은신뢰도 66.67% 의우울경향, 21점이상은신뢰도 85% 의우울증으로진단되며항우울제를고려한다 [26]. 6) 노인스트레스척도 (geriatric stress scale, GSS) 총 24개의문항으로가족문제, 경제적문제, 소외문제, 후회문제, 건강문제등 5가지를스트레스요인으로분류하여평가한다. 9개의문항은부정형으로스트레스척도를측정하고 15
108 Dae Jin Kim, et al. A Correlation between Cognitive Impairment and GDS or GSS 개의문항은긍정형으로스트레스척도를측정하도록되어있고, 0 72 점으로점수화하여높을수록스트레스가높다는것을의미한다. 3. 통계처리 SPSS version 20.0 통계프로그램 (SPSS Inc., Chicago, IL, USA) 을사용하였다. 연령, 성별, 학력등의인구통계학적기준을사용하여각그룹별기술통계량분석을실시하였다. 또한각그룹에대한인지기능장애와노인성우울, 노인성스트레스의차이를비교하기위해 Kruskall-Wallis 로확인하였고, Games- Howell 검증방법으로사후분석을시행하였다. 또한노인성우울과노인성스트레스가인지장애에미치는영향과노인성스트레스가노인성우울에미치는영향을알아보기위해상관분석과다중회귀분석을시행하였다. 연구의모든통계분석에따른유의수준은 P<0.05로정하였다. 결과 1. 인지기능 (K-MMSE, CDR, FAB, K-IADL), 노인우울증 (GDS), 노인스트레스 (GSS) 의평가본연구에서사용한인지기능변수들중 K-MMSE와 FAB 는값이작을수록, CDR과 K-IADL은값이높을수록심한인지장애를의미한다. 또한우울증변수인 GDS와스트레스변수인 GSS는값이높을수록심한우울증과스트레스를의미한다. 집단간인지기능변수들을비교한결과두치매군이정상군보다심한인지장애를보였고 (P<0.001), 집단간 GDS와 GSS 를비교한결과 VD군이 AD군과정상군에비해심한우울과스트레스정도를보였다 (P<0.001). 그러나 GSS 변수를세부적인원인으로분석한결과 VD군이 AD군과정상군에비해가족문제, 경제적문제, 소외문제에서만유의한차이가있는것으로나타났다 (P<0.001) (Table 2). 2. 인지기능 (K-MMSE, CDR, FAB, K-IADL) 과노인우울증 (GDS), 노인스트레스 (GSS) 의상관관계전체대상군에서인지기능변수와각 GDS, GSS의상관관계를분석한결과 K-MMSE와 FAB에서는음의상관관계 (GDS= 0.268, 0.287) (GSS= 0.191, 0.209) 를, CDR과 K-IADL에서는양의상관관계 (GDS=0.252, 0.366) (GSS=0.182, 0.263) 를보였다. 세부적으로 AD군에서는 K-MMSE와 FAB 에서는음의상관관계 (GDS= 0.281, 0.345) (GSS= 0.299, 0.308) 를, CDR과 K-IADL에서는양의상관관계 (GDS=0.253, 0.390) (GSS=0.231, 0.300) 를보였다. 특히성별로분류한경우 CDR 과 GSS의상관관계를제외하고나머지인지기능변수들에서 GDS와 GSS가남성에서만통계적으로유의한상관관계를확인하였다. 그러나또다른치매분류인 VD군에서인지기능변수와각 GDS, GSS의유의한상관관계확인할수없었고, 정상군에서도 GDS는 FAB, K-IADL, GSS는 K-IADL 에서만유의한상관관계를보였고, 나머지인지기능변수들에서는유의한상관관 Table 3. Evaluation of cognitive impairment, GDS and GSS for study participants Characteristics Division Total AD group (a) VD group (b) Normal (c) F or 2 (P) Post-hoc K-MMSE 19.3±6.6 15.4±4.3 15.4±4.1 27.1±1.5 <0.001 a=b<c CDR 1.2±0.8 1.6±0.8 1.5±0.8 0.5±0.1 <0.001 a=b>c FAB 10.1±4.8 7.2±3.2 7.9±3.9 15.3±2.1 <0.001 a=b<c K-IADL 1.4±1.1 1.9±0.9 2.0±0.9 0.2±0.3 <0.001 a=b>c GDS 15.8±7.8 14.9±7.6 18.9±7.8 13.6±7.0 <0.001 a=c<b GSS* 9.8±6.1 8.3±5.6 12.6±5.8 8.5±5.0 <0.001 a=c<b Factor1 2.6±2.3 2.0±2.0 3.4±2.4 2.3±2.1 <0.001 a=c<b Factor2 1.8±1.7 1.5±1.6 2.6±1.6 1.2±1.5 <0.001 a=c<b Factor3 2.2±2.0 2.1±2.0 3.0±2.1 1.6±1.7 <0.001 a, c<b Factor4 1.0±1.1 0.7±1.0 1.1±1.2 1.0±1.0 0.058 Factor5 2.1±1.4 1.9±1.5 2.3±1.3 2.0±1.4 0.163 Data are presented as mean±sd and number. Continuous value was performed with Kruskall-Wallis. Post-hoc test was performed with Games-Howell. *Geriatric stress scale category: Factor 1=family problem; Factor 2=finance problem; Factor 3=communication power problem; Factor 4=regret problem; Factor 5=health problem. Abbreviations: AD, Alzheimer s disease; VD, vascular dementia; K-MMSE, Korean version of mini-mental state exam; CDR, clinical dementia rating; FAB, frontal assessment battery; K-IADL, Korean instrumental activities of daily life; GDS, geriatric depression scale; GSS, geriatric stress scale.
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 109 계를확인할수없었다 (Table 3). 3. 노인우울증 (GDS) 과노인스트레스 (GSS) 의인지기능 (K-MMSE, CDR, FAB, K-IADL) 과인과관계전체대상군에서인지기능변수와각 GDS, GSS의인과관계 를분석한결과 GDS만인지기능변수들과의인과관계를보였다 (P=0.006, 0.013, 0.003, <0.001). 또한세부적으로도 AD 군에서 GDS만 K-MMSE, CDR, K-IADL 과의인과관계를보였고 (P=0.045, 0.045, 0.006), 정상군에서는 GDS만 K-IADL과의인과관계가확인되었다 (P<0.001) (Table 4). Table 4. Correlation between cognitive impairment, GDS and GSS Characteristics Total AD group VD group Normal GDS GSS GDS GSS GDS GSS GDS GSS K-MMSE Total 0.268** 0.191** 0.281* 0.299 0.127 0.069 0.030 0.045 Male 0.344** 0.201* 0.549** 0.403* 0.238 0.166 0.119 0.093 Female 0.184* 0.151 0.015 0.033 0.111 0.000 0.077 0.134 CDR Total 0.252** 0.182** 0.253* 0.231* 0.101 0.079 0.003 0.086 Male 0.288** 0.130 0.372* 0.287 0.165 0.007 0.175 0.246 Female 0.195* 0.195* 0.024 0.024 0.127 0.194 0.254 0.174 FAB Total 0.287** 0.209** 0.345** 0.308** 0.053 0.062 0.268* 0.119 Male 0.383** 0.171 0.510** 0.478** 0.176 0.014 0.519** 0.045 Female 0.191* 0.219* 0.097 0.001 0.017 0.155 0.095 0.195 K-IADL Total 0.366** 0.263** 0.390** 0.300** 0.192 0.121 0.330** 0.245* Male 0.410** 0.303** 0.543** 0.425* 0.265 0.292 0.240 0.379* Female 0.285** 0.193* 0.144 0.095 0.108 0.102 0.407** 0.124 Calculated by Spearman correlation coefficient. *P<0.05, **P<0.01. Abbreviations: See Table 3. Table 5. Multiple regression analysis the impact of cognitive impairment on GDS and GSS Characteristics Independent variable Dependent variable B SE t P F R 2 Adj R 2 Total GDS K-MMSE 0.184 0.067 0.217 2.75 0.006** 8.086* 0.064 0.056 GSS 0.057 0.086 0.053 0.665 0.507 GDS CDR 0.021 0.008 0.2 2.513 0.013* 6.462* 0.052 0.044 GSS 0.005 0.011 0.041 0.52 0.604 GDS FAB 0.147 0.048 0.239 3.04 0.003** 9.381* 0.073 0.066 GSS 0.038 0.062 0.048 0.609 0.543 GDS K-IADL 0.041 0.011 0.292 3.801 <0.001*** 15.572* 0.116 0.109 GSS 0.013 0.014 0.072 0.943 0.347 AD group GDS K-MMSE 0.216 0.121 0.423 1.788 0.045* 2.08 0.134 0.069 GSS 0.107 0.251 0.1 0.424 0.675 GDS CDR 0.046 0.022 0.492 2.102 0.045* 2.413 0.152 0.089 GSS 0.04 0.045 0.208 0.89 0.382 GDS FAB 0.161 0.098 0.378 1.634 0.114 2.766 0.17 0.109 GSS 0.044 0.205 0.05 0.215 0.831 GDS K-IADL 0.078 0.026 0.637 3.001 0.006** 5.842* 0.302 0.25 GSS 0.039 0.054 0.153 0.719 0.478 Normal GDS K-MMSE 0.053 0.039 0.246 1.361 0.181 0.963 0.046 0.002 GSS 0.047 0.05 0.17 0.942 0.352 GDS CDR 0.003 0.004 0.147 0.805 0.425 0.569 0.028 0.021 GSS 0.005 0.005 0.186 1.017 0.315 GDS FAB 0.093 0.053 0.314 1.761 0.086 1.55 0.072 0.026 GSS 0.065 0.069 0.168 0.941 0.352 GDS K-IADL 0.027 0.007 0.601 4.106 <0.001*** 12.005* 0.375 0.344 GSS 0.001 0.008 0.021 0.146 0.885 Calculated by multivariable linear regression analysis. *P<0.05, **P<0.01, ***P<0.001. Abbreviations: See Table 3.
110 Dae Jin Kim, et al. A Correlation between Cognitive Impairment and GDS or GSS 4. 노인스트레스 (GSS) 의우울증 (GDS) 과인과관계 Table 3에서 AD군은 GDS, GSS가인지기능변수와유의한상관성을확인하였지만, Table 4에서 AD군은 GDS만 K-MMSE, CDR, K-IADL 에유의하게영향을미칠수있는원인이라는결과가나왔다. 즉 GSS의경우인지기능변수와상관성은확인되나, 영향을미칠수있는원인이라고는단정할수없다. 그러나이전연구에따르면스트레스가치매의위험요소로확인되었고 [27-29], 스트레스와우울의연관성 [30] 도확인되었다. 이에본연구자들은 GSS가 GDS에미치는영향을확인하면. 간접적으로 GSS와인지기능변수들과의연관성을예측할수있을것으로사료되어 GSS와 GDS를다중회귀분석을실시하였다. 그결과전체대상군과 AD군, 정상군에서 GSS와 GDS 의인과관계를확인되었다 (P<0.001). 특히 GSS를세부적인원인별로분석한결과전체대상군에서는가족, 소외, 건강 (P= <0.001, <0.001, 0.005) 에서, AD군에서는가족, 소외 (P=0.005, 0.003) 에서, 정상군에서는소외 (P=0.021) 에서각각인과관계를확인하였다 (Table 5). 매는우울증이인지기능에영향을미치는것으로보인다. 또한스트레스는우울증에영향을미치는것으로확인되며, 간접적으로알츠하이머성치매의원인이될수있을것으로예측된다 (Figure 1). 특히가족문제와소외문제가중요한원인이될수있다 (Table 6). 의학의발달과삶의질이높아짐에따라고령화속도가빨라 고찰 본연구에서나타난혈관성치매는우울증과스트레스가높지만, 인지기능과의연관성은관찰할수없고, 알츠하이머성치 Figure 1. Flow diagram of association between cognitive impairment and GDS or GSS. (A) Alzheimer s disease. (B) Vascular dementia. Table 6. Multiple regression analysis the impact of GDS on GSS Characteristics Independent variable Dependent variable B SE t P F R 2 Adj R 2 Total GSS GDS 0.775 0.066 0.607 11.769 <0.001*** 138.519* 0.368 0.365 Factor 1 0.8 0.206 0.234 3.886 <0.001*** 33.03* 0.414 0.401 Factor 2 0.111 0.294 0.024 0.376 0.707 Factor 3 1.521 0.247 0.393 6.146 <0.001*** Factor 4 0.265 0.424 0.037 0.624 0.533 Factor 5 0.952 0.335 0.17 2.842 0.005** AD group GSS GDS 0.798 0.122 0.595 6.545 <0.001*** 42.837* 0.355 0.346 Factor 1 1.185 0.408 0.319 2.904 0.005** 9.784* 0.398 0.357 Factor 2 0.26 0.525 0.056 0.495 0.622 Factor 3 1.287 0.422 0.335 3.048 0.003** Factor 4 0.319 0.795 0.041 0.401 0.689 Factor 5 1.086 0.601 0.208 1.805 0.075 Normal GSS GDS 0.559 0.12 0.467 4.661 <0.001*** 21.727* 0.218 0.208 Factor 1 0.688 0.425 0.207 1.62 0.11 Factor 2 0.241 0.648 0.052 0.373 0.71 Factor 3 1.165 0.495 0.277 2.353 0.021* 5.075* 0.255 0.205 Factor 4 0.005 0.917 0.001 0.006 0.995 Factor 5 0.708 0.636 0.136 1.114 0.269 Calculated by multivariable linear regression analysis. *P<0.05, **P<0.01, ***P<0.001. Abbreviations: See Table 3.
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 111 지고있고, 그에따른노인성질환도증가하고있다. 노인성질환의대표적인치매는환자뿐만아니라부양가족에게도경제적, 정신적으로고통의부담이있기에조기발견이중요하며, 더나아가발병원인을찾아예방하는것이더욱중요하다. 본연구에서는치매를유발원인에따라 AD군과 VD군으로구분하고정상군을포함하여세군간의인지기능저하를측정하는변수들과우울증, 스트레스의차이점과, 인지기능변수와우울증, 스트레스의연관성도확인하였다. 집단간해당변수의차이점을보면, 인지기능변수들에서는두치매군이정상군에비해서높은인지기능장애를보였지만 GDS, GSS에서는 VD군이 AD군과정상군에비해서높은우울증과스트레스를보였다. 이는이전의연구결과와같이우울증은 AD와비특이성치매보다 VD에서좀더일반적인견해라는점과같은결과로확인되었다 [13]. 또한이전의연구들에서는확인할수없었던 GSS 를요인분석한결과는 VD 환자들이다른집단보다가족문제, 경제문제, 소외문제의스트레스요인이높다는점을확인하여객관적으로노인성스트레스해소를위해관심을가져야할부분이라사료된다 (Table 2). GDS, GSS와인지기능변수들과의상관성은대체적으로 AD 군에서만나타났다. 특히 GDS는남성에서만인지기능변수들과상관성이있고 (Table 3), GDS가인지기능변수들에영향을미치는원인으로확인되었다 (Table 4). 위의결과는명확하지않은우울증으로인한치매의발현 [10] 을뒷받침할수있는결과로사료되며, 남성에서국한된다는것을증명하였다. 이전의연구에서는성별에따른우울증과인지기능의연관성에대해많이언급되지않았지만, Fuhrer에따르면 [31] 남성에서고혈압과같은혈관의병리학적인문제로인한우울증은 AD의증상이악화되는것을가속시킬수있고, 최근발생한우울증에서만국한된다고한다. 이는남성에서만우울증과인지기능변수들과연관성이있다는본연구를뒷받침할수있을것이고, 우울증을기간별로세분화할필요성을제시하였다. GSS의경우다른연구결과 [28, 30] 와같이인지기능과의연관성은있었지만 (Table 3), 영향을미치는원인이라고는할수없다 (Table 4). 그러나 Table 5에서보면 GSS의경우 GDS에영향을미치는원인이라는결과를보면, 스트레스는직접적으로인지기능장애의원인은될수없으나, 노인성우울을유발할수있고그로인하여인지기능장애에간접적으로영향을미치는것으로예측할수있는부분이다. 이는우울증을감소시키는것도치매예방에도움은되지만, 스트레스가우울증의원인이기에우선적으로관리해야된다고사료된다. 결론적으로치매를조기진단하는것은매우중요하며노인성우울의평가를통해서 AD는어느정도예측가능할수있고, 예방적인차원에서노인성스트레스의관 리가필요하다. 그러나본연구의제한점은다음과같다. 첫째로다른질환을갖지않은대상자들의인구통계학적인기준으로만분류하여조사되어, 가족력과치매와연관된생활정도, 직업등사회력과결부되어좀더세분화하지못해추가적인연구가필요할것이다. 둘째로치매는환자뿐만아니라가족의역할이매우중요하다. 이번연구에서는단편적인환자의인지기능과우울증, 스트레스와의연관성을확인하였지만가족과의관계, 가족들의스트레스와우울정도등을복합적으로분석하는것이좀더완성도높은연구가될것이라사료된다. 요약본연구의목적은노인성우울, 노인성스트레스와인지기능과의연관성을확인하는것이다. 구체적으로치매를유발원인에따라알츠하이머성치매와혈관성치매의두그룹으로분류하고각그룹의인지장애및노인성우울, 노인성스트레스의정도와특성의차이를확인하고상호간의연관성을비교하고자한다. 인지기능의변수는한국형간이정신상태검사, 치매임상평가척도, 이마엽기능검사, 한국형도구적일상생활능력평가를사용하였고, 노인성우울변수는노인우울척도 (GDS), 노인성스트레스변수는노인스트레스척도 (GSS) 를사용하였다. 통계적방법은알츠하이머성치매환자 80명, 혈관성치매환자 80 명, 통제를위한정상군 80명을설정하여기술통계량, Kruskall-Wallis, 상관분석, 다중회귀분석으로통계적으로유의한차이및연관성을확인하였다. 알츠하이머성치매군에서는 GDS, GSS와대체적으로인지기능변수들과의상관관계는확인하였다. 특히 GDS는남성에서만인지기능변수들과상관관계가있고, 인지기능변수들과의인과관계도확인되었다. 또한 GSS와 GDS와의인과관계를확인하여 GSS가 GDS의원인이된다는유의성을확인하였다. 결론적으로 GDS는알츠하이머성치매군에서인지기능변수와의상관관계와직접적인인과관계를확인하였고, GSS는직접적인상관관계보다 GDS를유발하여인지기능장애와의간접적인인과관계를확인할수있었다. Acknowledgements: None Conflict of interest: None Author s information (Position): Kim DJ 1,, M.T.; Cho SY 2,, M.T.; Choi JS 3, Graduate student; Lee MW 4, Adjunct professor; Cho EK 5, M.T.; Kang SH 2,6, M.T.; Kim SW 6, Professor.
112 Dae Jin Kim, et al. A Correlation between Cognitive Impairment and GDS or GSS REFERENCES 1. Dening T, Babu Sandilyan M. Dementia: definitions and types. Nurs Stand. 2015;29:37-42. http://doi.org/10.7748/ns.29.37.37. e9405. 2. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, et al. Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA. 1989;262: 2551-2556. http://doi.org/10.1001/ jama.1989.03430180093036. 3. Chui HC, Victoroff JI, Margolin D, Jaqust W, Shankle R, Katzman R, et al. Criteria for the diagnosis of ischemic vascular dementia proposed by the state of California Alzheimer's disease diagnostic and treatment centers. Neurology. 1992;42:473-480. http://doi.org/10.1212/wnl.42.3.473. 4. McPherson SE, Cummings JL. Neuropsychological aspects of vascular dementia. Brain Cogn. 1996;31:269-282. http://doi.org/10.1006/brcg.1996.0045. 5. Oh BH. Diagnosis and treatment for behavioral and psychological symptoms of dementia. J Korean Med Assoc. 2009;52:1048-1054. http://doi.org/10.5124/jkma.2009.52.11.1048. 6. Finkel SI, Silva JC, Cohen GD, Miller S, Sartorius N. Behavioral and psychological symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Am J Geriatr Psychiatry. 1998;6:97-100. http://doi.org/10.1097/00019442-199805000-00002. 7. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease: disorders of behavior. Br J Psychiatry. 1990;157:86-91. http://doi.org/10.1192/bjp.157.1.86. 8. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44:2308-2314. http://doi.org/10.1212/wnl.44.12.2308. 9. Cummings JL, Miller B, Hill MA, Neshkes R. Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type. Arch Neurol. 1987;44:389-393. http://doi.org/ 10.1001/archneur.1987.00520160031010. 10. Korczyn AD, Halperin I. Depression and dementia. J Neurol Sci. 2009;283:139-142. http://doi.org/10.1016/i.ins.2009.02.346. 11. Ryu KH, Kang YW, Na DL, Lee KH, Chung CS. The characteristics of depression in dementia patients. Kor J Clin Psychol. 2000;19:117-129. 12. Nilsson FM, Kessing LV, Sorensen TM, Andersen PK, Bolwig TG. Enduring increased risk of developing depression and mania in patients with dementia. J Neurol Neurosurg Psychiatry. 2002; 73:40-44. http://doi.org/10.1136/jnnp.73.1.40. 13. Castilla-Puentes RC, Habeych ME. Subtypes of depression among patients with Alzheimer s disease and other dementias. Alzheimer s Dement. 2010;6:63-69. http://doi.org/10.1016/j. jalz.2009.04.1232. 14. McEwen BS, Sapolsky RM. Stress and cognitive function. Curr Opin Neurobiol. 1995;5:205-216. http://doi.org/10.1016/0959-4388(95)90028-x. 15. 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;43:250-260. http://doi.org/10.1212/wnl.43.2. 250. 16. Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological assessment. 5th ed. New York: Oxford University Press; 2012. 17. Folstein MF, Folstein SE, McHugh PR. Mini-mental state : a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198. http://doi.org/10.1016/0022-3956(75)90026-6. 18. Kang YO, Na DR, Hahn SH. A validity study on the Korean mini-mental state examination in dementia patients. J Korean Neurol Assoc. 1997;15:300-308. 19. Han C, Jo SA, Jo I, Kim E, Park MH, Kang Y. An adaptation of the Korean mini-mental state examination (K-MMSE) in elderly Koreans: demographic influence and population-based norms (the AGE study). Arch Gerontol Geriatr. 2008;47:302-310. http://doi.org/10.1016/j.archger.2007.08.012. 20. Shin HH, So HY, Lee AY. Comparing clinical usefulness of cognitive function tests (CDT, K-MMSE, K-3MS, CDR) in dementia patient. Korean J Rehabil Nurs. 2008;11:90-98. 21. 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;19:585-591. 22. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43:2412-2414. http://doi.org/10.1212/wnl.43.11.2412-a. 23. Slachevsky A, Villalpando JM, Sarazin M, Hahn-Barma V, Pillon B, Dubois B. Frontal assessment battery and differential diagnosis of frontotemporal dementia and Alzheimer disease. Arch Neurol. 2004;61:1104-1107. http://doi.org/10.1001/archneur. 61.7.1104. 24. Kim TH, Huh Y, Choe JY, Jeong JW, Park JH, Lee SB, et al. Korean version of frontal assessment battery: psychometric properties and normative data. Dement Geriatr Cogn Disord. 2010;29:363-370. http://doi.org/11.1159/000297523. 25. Kang SJ, Choi SH, Lee BH, Kwon JC, Na DL, Han SH, el al. The reliability and validity of the Korean Instrumental Activities of Daily Living (K-IADL). J Korean Neurol Assoc. 2002;20:8-14. 26. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatric Res. 1983;17:37-49. http://doi.org/10.1016/0022-3956(82)90033-4. 27. Wang HX, Wahlberg M, Karp A, Winblad B, Fratiglioni L. Psychosocial stress at work is associated with increased dementia risk in late life. Alzheimer s Dement. 2012;8:114-120. http://doi.org/10.1016/j.jalz.2011.03.001. 28. Flatt JD, Gilsanz P, Quesenberry CP, Albers KB, Whitmer RA. Post-traumatic stress disorder and risk of dementia among members of a health care delivery system. Alzheimer s Dement. 2017;14:28-34. http://doi.org/10.1016/j.jalz.2017.04.014. 29. Greenberg MS, Tanev K, Marin MF, Pitman RK. Stress, PTSD, and dementia. Alzheimer s Dement. 2014;10:155-165. http://doi.org/10.1016/j.jalz.2014.04.008. 30. Bos EH, Bouhuys AL, Geerts E, van Os TW, Ormel J. Stressful life events as a link between problems in nonverbal communication and recurrence of depression. J Affect Disord.
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 113 2007;97:161-169. http://doi.org/10.1016/j.jad.2006.06.011. 31. Fuhrer R, Dufouil C, Dartigues JF, PAQUID Study. Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID study. J Am Geriatr Soc. 2003;51:1055-63. http://doi.org/10. 1046/j.1532-5415.2003.51352.x.