(이준석-박종호) hwp
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1 원저 관동대학교의과대학명지병원신경과학교실, 정신과학교실 a 박종호이준석 a 심종온 a 이종명 a Power Spectral Analysis of Resting EEG in Elderly Patients With Dementia of Alzheimer and Those With Major Depression in Comparison With Normal Healthy Control Jong-Ho Park, MD, Jun-Seok Lee, MD, PhD a, Jong-On Shim, MS a, Jong-Myung Lee, MS a Department of Neurology and Psychiatry a, Kwandong University College of Medicine, Myongji Hospital, Goyang, Korea Background: Depression is one of the most frequent neuropsychiatric comorbidities of dementia of Alzheimer type (DAT). The aim of the present study was to compare the quantitative EEG changes in patients with DAT with those in old age depression (OAD). Methods: We recruited 39 subjects (mean age=65.4±5.9, 30 women, 13 DAT, 13 OAD, and 13 healthy controls) and performed the absolute and relative power spectral analyses for delta, theta, alpha, and beta activities. Results: The DAT group showed higher frequency of delta in all the topographic areas than the OAD and controls (p<0.05). Delta activity was more frequent in the DAT than OAD group in the bilateral central (, ) and temporal areas (, ) (p<0.05). Compared with the controls, the DAT group showed decreased alpha activity in the left central () and temporal () areas (p<0.05). Beta activity was increased in the OAD group ( and ), compared with that in the other two groups (p<0.05). Conclusions: Spectral analysis showed more prominent delta slowing in the DAT group, which is in line with more severe cognitive dysfunction in the DAT than the OAD group. J Korean Neurol Assoc 26(3): , 2008 Key Words: Electroencephalography, Spectral analysis, Cognitive performance, Dementia of Alzheimer type, Old age depression 서론 알츠하이머형치매 (dementia of Alzheimer type, DAT) 와 Received February 29, 2008 Revised July 7, 2008 Accepted June 4, 2008 *Jun-Seok Lee, MD, PhD Department of Psychiatry, Myongji Hospital, Kwandong University College of Medicine, Hwajeong-dong, Deokyang-gu, Goyang-si, Gyeonggi-do, , Korea Tel: Fax: mdjslee@kd.ac.kr * 본논문은 2006년도정부 ( 교육인적자원부 ) 의재원으로한국학술진흥재단의지원을받아수행된연구임 (KRF-2006-E00071). 노년기우울증 (old-age depression, OAD) 은감별진단에서흔히문제가되는질환들이다. 1 이들두질환의관련성에대해서다양한주장이존재하는데, 초기주장은치매와우울증이완전히별개의독립된질환이라는것이었다. 2 이후 Reifler 등은두질환이흔히공존하는질환이며치매의한요소로서혹은합병증으로서노년기우울증이나타난다고하였으며, 3 보다최근에는 DAT 와 OAD 는서로상호작용을하는질환으로서가역적인인지기능감퇴를동반한 OAD 는치매의전조라는주장까지제기되고있다. 4 또한이들두질환은높은중복이환 (comorbidity) 을보이는데, DAT 의약 41% 에서우울증상을보이고, 4 OAD 의약 60% 216 대한신경과학회지제 26 권제 3 호, 2008
2 에서경도인지장애 (mild cognitive impairment, MCI) 를동반한다고보고되었다. 5 이렇게높은중복이환은진단기준과도관련되는데, DAT 에서나타나는우울증상에대해 DSM-III (American Psychiatric Association, 1987) 에서는 기질성정신장애 에서기인된다고판단되는우울증상에대해서주요우울삽화의진단을배제시켰으나, DSM-IV (1994) 에서는주요우울증이비가역적치매와공존할수있다고허용하였다. 이러한진단기준의변화는인지기능의감퇴를비롯하여초조, 정신증, 식욕및수면변화, 흥미의감소등주요증상들을공유하는 OAD 와 DAT 의중복이환을높이는요인이되었다. 이러한문제를인식하여미국국립정신보건원 (National Institute of Mental Health) 에서는 DAT 에서우울증의진단기준 (National Institute of Mental Health Provisional Diagnostic Criteria for Depression of Alzheimer s Disease; NIMH-dAD) 을개발하였으나, DAT 가진행될수록우울장애가과도하게진단되고, 우울장애의아형별분류가어렵다는점등여러단점이지적되었다. 6 DAT 와 OAD 는높은공존이환율과주요증상의공유로인하여감별진단의어려움에도불구하고반드시정확한진단이요구되는질환들이다. DAT 에대한정확한진단이지연되어조기치료가이루어지지못할경우인지기능의저하를방치할수있고, 인지기능감퇴를동반한 OAD 를 DAT 혹은 MCI 와혼동할경우우울증상을심화시킬가능성이있다. 인지기능의감퇴를나타내는두질환의진단에서가장문제가되는것은신뢰할만한진단적표식자가부재한다는것이다. 이런맥락에서비교적간편하고, 경제적이며, 무엇보다비침습적인검사도구인뇌파를이용하여치매나우울증의진단적표식자를찾기위한많은연구보고들이있었다. 이미 1932 년 Hans Berger 가치매환자의각성뇌파에서서파화를발견하여정상적인노인의뇌파와비교하여보고한이래뇌파는오랫동안치매환자의임상적평가에서중요한검사도구로이용되어왔다. 7 더불어우울증영역에서도다양한뇌파연구가이루어졌는데, 뇌파를연구하는다양한기법들가운데현재까지가장주된방법은스펙트럼분석이라고할수있다. 이전의스펙트럼분석연구들에서 DAT 에서는델타 (delta) 파와세타 (theta) 파가증가하고, 알파 (alpha) 파나베타 (beta) 파가감소되는것으로보고되었다 이에비하여 OAD 환자는알파파가증가하거나 13 감소하는 14 등상반된견해들이보고되었고, 일부연구에서는측두엽에서세타파가증가한다고보고하였다. 15 이와같이 DAT 나 OAD 환자를대상으로뇌파의스펙트럼분석을실시한연구들이국외에서는많이보고되었으나국내의연구보고는미미한실정이다. 이에저자들은국내환자들을대상으로 DAT 와 OAD 환자의스펙트럼분석을통하여두질 환의특징적인뇌파소견을살펴보고감별진단에도움이되는전기생리학적표식자를찾아보고자하였다. 대상과방법 1. 대상 연구대상군의자료는 2006 년 9월부터 2007 년 1월까지관동대학교명지병원을방문한 DAT 및 OAD 환자들을대상으로하였다. DAT 환자군은기억력감퇴를주소로내원한환자들로서, 이전에 DAT 치료제및기타내과적치료제를복용한과거력이없으면서, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association (NINCDS-ADRDA) 16 기준을만족시킨경우연구대상에포함시켰다. OAD 환자군은이전에항우울제약물치료를받은과거력이없으면서 DSM-IV (1994) 기준에따라주요우울장애로진단된경우포함하였다. 뇌파를측정하기직전에인지기능및우울증상의심각도를조사하였다. 대뇌의기질적이상을배제하기위하여모든대상자에게뇌 MRI 를시행하였으며, 전신신체질환을배제하기위하여전체혈구계산 (complete blood count, CBC), 갑상샘촉진호르몬 (thyroid stimulation hormone), 자유 (free ), 간기능검사 (AST, ALT), 신장기능검사 (BUN, creatinin) 등을포함하는혈액학적검사를시행하였다. 인지기능척도는한국형간이정신상태검사 (mini mental state examination-korean version, MMSE-K) 17 를이용하였다. 우울증상을평가하기위해서 Beck우울척도 (Beck Depression Inventory, BDI), 항목해밀튼우울평가척도 (Hamilton Rating Scale for Depression, HDRS), 19 노인우울척도 (Geriatric Depression Scale, GDS) 20 등을사용하였다. 그밖에불안증상을평가하기위하여해밀튼불안척도검사 (Hamilton Rating Scale for Anxiety, HARS) 21 를사용하였다. 첫면담시 (1) DSM-IV 에서주요우울장애의진단기준을만족시키면서, (2) BDI 와 HDRS 에서 14 점이상이고, (3) MMSE- K에서 25점이상인경우를 OAD 환자로포함시켰다. DAT 환자군에서는 (1) NINCDS-ADRDA 에서 DAT 의진단기준을만족시키면서, (2) BDI 와 HDRS 에서 14점미만이고, (3) MMSE-K 에서 24점이하인경우를포함하였다 (Table 1). 정상대조군 (healthy control, HC) 은나이와성별을일치시킨병원근무자를대상으로모집하였으며 BDI 와 HDRS 점수가 14점미만이면서, MMSE-K 점수가 25점이상인경우를포함시켰다. DAT, OAD 및 HC에적용된배제기준은다음과같았는데, J Korean Neurol Assoc Volume 26 No. 3,
3 박종호이준석심종온이종명 Table 1. Comparison of demographic and clinical characteristics in patients with DAT, OAD, and healthy control DAT OAD HC p value Post hoc t-test Female 10 (76.9) 10 (76.9) 10 (76.9) Age (yr) 66.4± ± ± MMSE-K 22.0± ± ±1.0 DAT<OAD a DAT<HC a BDI 6.7± ± ±3.5 OAD>DAT a OAD>HC a HDRS 8.8± ± ±4.3 OAD>DAT a OAD>HC a GDS 10.1± ± ±7.5 OAD>DAT a OAD>HC a HARS 11.3± ± ± OAD>HC b Values are mean±sd or number (percentage) of patients. p values were for the comparison between three groups and were obtained using the one-way ANOVA test for continuous data, and the Chi-square test for categorical data. a p by Bonferroni method, b p<0.05 by Bonferroni method. BDI; Beck depression inventory, DAT; dementia of Alzheimer type, GDS; geriatric depression rating scale, HARS; Hamilton rating scale for anxiety, HC; healthy control, HRDS; Hamilton rating scale for depression, MMSE-K; mini-mental state examination Korean version, OAD; old age depression. (1) 정신분열병 ( 혹은기타정신병 ), 반사회적인격장애, 알코올혹은약물남용및의존 (2) 망상, 환각의증거가있거나심각한자살위험이상존하는경우 (3) 경련, 뇌수술, 기질적뇌질환혹은기질성정서장애의과거력및뇌 MRI 에서뇌위축이외의이상소견을보인경우 (4) 임상적으로의미있는신경학, 소화기, 간, 신장, 혈액학혹은호흡기질환의과거력및혈액학적검사에서이상소견을보인경우 (5) 지난 4주간항우울제 (fluoxetine 의경우 8주 ), 벤조다이아제핀제제, 바르비튜레이트제제, 베타수용체길항제, 시메티딘, 클로니딘, 항응고제혹은 DAT 치료제등중추신경계작용약물들을복용한경우에는연구대상에서제외시켰다. 본연구는병원의 IRB 를통과하였으며연구에참여하는모든대상자에게검사의목적을충분히설명한후에서면동의서를받았다. 2. 뇌파측정외부환경의방해나간섭을피하기위하여구리로차폐된뇌파기록실에서디지털뇌파기 (Laxtha Inc, QEEG-8, LEX 3208) 를이용하여눈을감은안정상태에서 5분간뇌파를측정하였다. 대상자의머리표피에 시스템에따른 8채널의뇌파를전두부 (, ), 중앙부 (, ), 측두부 (, ), 후두부 (, ) 에전극을부착하여우측귀를기준전극 (reference load) 으로이용하여측정하였다. 모든전극의임피던스는 5 kω 이하로하였고, 표본추출속도는 256 Hz/channel, 12-bit A/D 변환기, 0.6 Hz 저위여과기 (lower filter), 46 Hz 고위여과기 (high filter), 단계여과기 (notch filter) 60 Hz 로설정하였다. 분석에사용된뇌파는폐안뇌파로안구나안면의움직임으로인한근전도인공물 (artifact) 등잡파 (noise) 가많이섞인경우에는자료를폐기하였다. 잡파가없는폐안뇌파를뇌파분석시스템인 Complexity 2.0 (Laxtha Inc, Daejeon, Korea) 을이용하여 fast Fourier 전환을시행하였고 power spectra 를구했다. 뇌파의절대파워 (magnitude) 치의제곱근이 microvolt (μv) 치로계산되었다. 스펙트럼분석은뇌파의절대파워, 상대파워를 4가지주파수영역에걸쳐구하였는데, 델타 = 1 ~ 3.5 Hz, 세타 = 4 ~ 7.5 Hz, 알파 = 8 ~ 12 Hz, 베타 = 13 ~ 25 Hz 영역으로분류하였다. 절대파워는주기별진폭의양을나타내며, 상태파워는특정주파수의전기적힘을전체영역에서의전기적힘으로나눈값을나타낸다. 이러한스펙트럼분석을통해절대파워와상대파워를측정하였다. 3. 통계분석 DAT 군, OAD 군, HC 군의차이는 SPSS 13.0 을이용하여 oneway ANOVA 검증을통하여통계분석을실시하였다. 상관관계를알아보고자 Pearson 상관검증을이용하였다. 모든분석에서 p value 가 0.05 미만일경우통계적으로유의한것으로판정하였다. One-way ANOVA 검증에서유의한차이를보인경우각각의군간차이의유의성을알아보고자, Bonferroni method 를이용하였다. 218 대한신경과학회지제 26 권제 3 호, 2008
4 Table 2. Correlation of EEG power spectrum with scales for cognition and depression Frequency Channel MMSE-K BDI HDRS GDS HARS Absolute Delta Theta Alpha Beta Relative Delta Theta Alpha Beta Statistical test was done by Pearson s correlation test. BDI; Beck depression inventory, GDS; geriatric depression rating scale, HARS; Hamilton rating scale for anxiety, HRDS; Hamilton rating scale for depression, MMSE-K; mini-mental state examination Korean version. J Korean Neurol Assoc Volume 26 No. 3,
5 박종호이준석심종온이종명 결과 와도유의한상관관계를보이지않았다. 1. DAT 군, OAD 군, HC군의인구학적및신경심리학적특성소견분석 4. 스펙트럼분석을통한 DAT 군, OAD 군과 HC군의뇌파변화비교 세군의인구통계학적및신경심리학적검사소견은표 1에나타내었다. 성별, 평균나이는세군간에유의한차이는없었다. 인지기능을평가하는 MMSE-K 는 DAT 군이 OAD 군과 HC 군에비해각각유의하게낮았다 (p, respectively). 우울의정도를측정하는 BDI, HRDS, GDS 모두 OAD 군에서 HC 군, DAT 군에비해유의하게높았다 (all p). 불안의정도를평가하는 HARS 는 OAD 군이 HC 군에비해의미있게높았지만 (p<0.05), DAT 군과는유의한차이를보이지않았다. 2. MMSE-K, BDI, HDRS, GDS, HARS의상관관계 BDI 점수와 HDRS, GDS, HARS 사이에는서로유의한긍정적상호연관성 (positive correlation) 를나타낸반면 (all p<0.01), MMSE-K 와는유의한상관관계가없었다. 3. 뇌파스펙트럼과인지기능척도 (MMSE-K), 우울척도 (BDI, HDRS, GDS) 및불안척도 (HARS) 와의관계전체대상군 (n=39) 에서뇌파스펙트럼의절대파워값및상대파워값과 MMSE-K, 우울및불안척도와의상관관계를구하였다 (Table 2). 델타파는절대파워및상대파워모두전채널에서 MMSE-K 와유의한부정적상호연관성 (negative correlation) 를보였다. 반면델타파와정서척도의상관관계에서는상대파워값이우측중앙부 () 에서만 HDRS 와부정적상호연관성을보인것이외에는우울평가척도인 BDI, HDRS, GDS 나불안평가척도인 HARS 가델타파와유의한상관관계를보이지않았다. 베타파에서절대파워값은측두엽을중심으로여러영역에서 BDI (, ), HDRS (,,,,, ) 와유의한상관관계를나타내었고, 양측후두부 (, ) 영역에서는 MMSE-K 와도유의한긍정적상호연관성을나타내었다. 한편베타파의상대파워값은 BDI (,,,, ), HDRS (,,,,, ), 그리고 GDS () 와긍정적상호연관성을나타낸반면, MMSE-K 와는어떠한상관관계도나타내지않았다. 알파파에서는상대파워값이좌측중앙부 () 와좌측측두엽 () 에서 MMSE-K 와긍정적상호연관성을보인것을제외하고는나머지세타와알파파의절대및상대파워는어느척도 뇌파의스펙트럼분석에서얻어진절대파워값의비교 (Table 3) 에서는베타파영역에서만유의한차이를나타냈는데, OAD 군에서좌측후두엽영역 () 의베타파절대파워값이유의하게증가된결과를보였다. T-검증에서는 OAD 군이 DAT 군에비해서는유의하게높았으나 HC군과는유의한차이가없었다. 나머지델타, 세타및알파파의절대파워에서는유의한차이가없었다. 세군의상대파워값에서델타파에서는 DAT 군이양반구전영역 (,,,,,,, ) 에서유의한차이를보였다 (p<0.05) (Table 3). 그중에서특히양측중앙부 (, ) 와양측측두엽 (, ) 영역에서는 DAT 군이 HC 군뿐만아니라 OAD 군에비해서도유의하게증가되었다 (Fig.). 알파파의상대파워값에서는좌측중앙부 () 와좌측측두엽 () 에서 DAT 군이 HC군에비해유의한감소를보였으나 (p<0.05), OAD 군과의차이는유의하지않았다. 베타파의상대파워값은양측후두엽 (, ) 에서 OAD 군이 DAT 군에비하여유의한증가를보였다 (p<0.05). 세타파의상대파워값에서는세군간에유의한차이가없었다. 고찰 뇌파는 DAT 환자에있어특징적인정보를제공하지는않지만치매증상을보이는다른원인이나질환을감별하는데있어 MRI 에상호보완적인검사로고려되기도한다. 22 본논문은 DAT 의인지능장애를반영하는신경생리학적표식자를밝히는것이목적이아니라, DAT 와인지기능저하를보이는 OAD 를보다객관적이고효율적으로감별하는데도움이되는표식자를파워스펙트럼분석을통하여제시해보려는의도의연구이다. 본연구대상자들은 MMSE-K 외에도실제로숫자외우기검사 (digit span test), 시각기억검사 (visual learning test), Rey- Kim 기억검사등을시행하였기에 ( 결과미기재 ) 인지기능평가에문제점이없도록하였다. 각질환에특징적인표식자를찾기위하여 DAT 와 OAD 가공존하지않는집단을선택하여정상대조군과비교하였다. 또한대상자들의성별및연령을맞추고뇌질환및신체질환, 뇌파에영향을미치는약물의복용등나이가증가함에따라서뇌파에영향을미칠수있는요인들을철저히통제한후안정뇌파의스펙트럼분석을실시하였다. 220 대한신경과학회지제 26 권제 3 호, 2008
6 Table 3. Comparison of absolute and relative power values in the delta, theta, alpha and beta frequency bands Frequency Absolute Delta Theta Alpha Beta Relative Delta Theta Alpha Beta Channel DAT 22.92± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.05 OAD 13.30± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.11 HC 10.92± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.05 p value Values are mean±sd or number (percentage) of patients. p values were for the comparison between three groups and were obtained using the one-way ANOVA test. a p<0.05 by Bonferroni method. DAT; dementia of Alzheimer type, HC; healthy control, OAD; old age depression. Post hoc t-test DAT>OAD a DAT>OAD a DAT>OAD a DAT>OAD a DAT<HC a DAT<HC a DAT<OAD a DAT<OAD a J Korean Neurol Assoc Volume 26 No. 3,
7 박종호이준석심종온이종명 DAT group OAD group HC group Figure. Graphical distribution of relative power value in delta frequency. DAT; dementia of Alzheimer type, HC; healthy control, OAD; old age depression. 본연구결과델타파, 알파파, 베타파의상대파워값에서세집단사이에유의한차이가나타났다. 먼저, 델타파의상대파워값은 DAT 군이 HC 군에비하여좌측전두엽 () 을제외한전영역에서유의하게높은결과를보였다. 이러한결과는 DAT 의병변이초기에는해마 (hippocampus) 나내후각피질 (entorhinal cortex) 에서시작하여신피질전반으로진행되는경과를거치기때문에 23 뇌파의변화도 DAT 의국소병변에국소적으로일치하는부위에서보이면서점차전반화된다는종래의보고들과일치한다. 24,25 또한양측중앙부 (, ) 와측두엽 (, ) 에서는 DAT 군이 OAD 군에비해서도델타파가유의하게증가되었는데, 이는가성치매를보인우울증이나순수우울증을보인환자들과우울증상을나타내는치매혹은치매증상만나타내는환자들을비교한결과우울증환자군에서는치매환자군에비해서파화 (slowing) 가동반되지않는정상소견이유의하게많았다는종래의보고와부합된다. 26 더욱이본연구에서 DAT 의특징적인델타파의절대및상대파워는인지기능을반영하는 MMSE-K 와부정적상호연관성을보였다. 이는 DAT 군에서의델타와세타파의정도가 Mini-mental score 를반영하는 Folstein 점수와부정적상호연관성을보인연구에일치되는결과이다. 27 이러한맥락에서델타파의상대파워값은우울증상을보이는 DAT 와기억장애를보이는 OAD 군을감별하는표식자로적용될수있다는가능성을시사한다. 다음으로알파파의상대파워값은 DAT 군이 HC에비하여좌측중앙부 () 와측두엽 () 영역에서유의하게낮은결과를나타내었다. 또한알파파의상대파워값이좌측중앙부 () 와좌측측두엽 () 에서 MMSE-K 와긍정적상호연관성을보였다. 이러한결과는초기 DAT 에서알파파의감소내지는부재가선행되고이후에델타파와세타파가증가된다는종래의보고들과일치한다 본연구에서 DAT 군에서보인 MMSE-K 점수의분포는 18에서 24점으로비교적질환의초기부터진행된단계까지분포되어있었기때문에 HC군에비하여알파파의 감소및델타파의증가가공존된것으로사료된다. 이에반하여베타파의상대파워값은 OAD 군이 DAT 군에비하여양측후두엽 (, ) 에서유의하게높은결과를나타내었다. 아울러베타파의절대파워값도좌측후두엽 () 에서 OAD 군이 DAT 군에비하여유의하게높았으며, 이러한 OAD 군의절대및상대파워값은모두 DAT 군뿐만아니라 HC군에비해서도높은결과를보였다. 베타파의증가는불안과관련되는것으로알려져있다. 31 불안증상은우울증상에매우흔히동반되는증상으로우울증상이심해질수록불안증상도함께증가되는경향이있다. 32 이는본연구에서베타파가우울과불안을반영하는척도와유의한상관관계를보인결과에부합된다. 최근의한연구에서실제주요우울장애환자에서불안장애를함께갖는비율은 60% 에이르는것으로보고되었다. 33 따라서본연구에서 OAD 군의베타파가증가한것은불안을동반한우울을반영한것으로사료된다. DAT 군이 OAD 군에비하여유의하게낮은베타파워를나타낸것은 DAT 군에서전형적으로나타나는뇌파의서파화특성 ( 델타파의증가와알파파, 베타파의감소 ) 과도일치한다 베타파의절대파워치가양측후두부 (, ) 영역에서 MMSE- K와정적상관관계를나타내었는데이또한치매가진행되어 MMSE-K 가감소할수록베타파가감소하는서파화의경향을반증하는것으로해석된다. 결론적으로본연구의결과는임상적으로호소하는증상이유사한경우에뇌파를통하여알파파의감소및델파파의증가를보이는경우 DAT 의가능성에초점을맞추고, 베타파의증가를동반하는경우에는 OAD 에초점을맞추어야한다는것을시사한다. 본연구의제한점은첫째, 종래의연구에비해대상환자수가비교적적었던점, 둘째, OAD 를 HC와감별할수있는표식자를찾지못했던점, 마지막으로단일대학병원외래환자들만을대상으로시행하였기때문에중증의 DAT 나 OAD 환자가 222 대한신경과학회지제 26 권제 3 호, 2008
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Sleep, EEG and mental function changes in senile dementia of the Alzheimer s type. Neurobiol Aging 1982;3: Kiloh LG, McComas AJ, Osselton JW, Upton A. Clinical Electroencephalography, fourth ed. Butterworths, London, UK, Lee JS, Yang BH, Oh DY, Kim KS. EEG A1, A2, and Percent Asymmetry Indices in Major Depressive Disorder: The Importance of Symptom Severity of Depression and Anxiety. J Korean Neuropsychiatr Assoc 2007;46: Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: J Korean Neurol Assoc Volume 26 No. 3,
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