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1 ORIGINAL ARTICLE pissn , eissn J of Oriental Neuropsychiatry 2014;25(3): 한방신경정신과영역의 Alzheimer 형치매관련연구현황 김태윤, 금창준, 오재우 자생한방병원한방신경정신과 The Current Status about Alzheimer s Dementia in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine Tae-Yoon Kim, Chang-Jun Kum, Jae-woo Oh Department of Neuropsychiatry, Jaseng Oriental Medical Hospital Received: September 1, 2014 Revised: September 16, 2014 Accepted: September 17, 2014 Correspondence to Tae-Yoon Kim Jaseng Oriental Medical Hospital, 635 Shinsa-dong, Gangnam-gu, Seoul, Korea. Tel: Fax: pacifier9@naver.com Acknowledgement This work was supported by Jaseng Oriental Medical Hospital. Objectives: Alzheimer's Dementia is somewhat common in clinical stages, and there are many reports and papers regarding this subject. We explain the present state of Alzheimer's Dementia in JON (The Journal of Oriental Neuropsychiatry) for the benefits of clinical practice. Methods: We searched for articles in JON from 1990 to 2014 and selected ones that were related to Alzheimer's Dementia; then, we analyzed the data and placed it in four categories, like experimental study, case study, Clinical Data-Analysis study, and clinical trial. Results: 1) We found 47 articles relating to Alzheimer's Dementia in JON from 1997 to 2014: 41 experimental studies, 1 case study, 1 Clinical Data-Analysis study, and 4 Clinical trials. 2) There were Chung-kyung Acupuncture Method, Auricular acupuncture, and Cha-rak Acupuncture Method to treat Alzheimer's Dementia. 3) There were many additional treatments, like aroma therapy. 4) In the experimental study, they reported on several herbs, including herbal prescriptions that affected the suppression of related mrnas and genes. 5) There were 4 clinical trials regarding herbal prescription that was effective for treating Alzheimer's Dementia. Conclusions: In JON, regarding Alzheimer's Dementia, the majority dealt with experimental studies. Therefore, we also have to expand our sight into other fields of study. We need more clinical trials and case studies for the treatment of Alzheimer's Dementia in Oriental Neuropsychiatry. Key Words: Alzheimer s Dementia, Dementia, Journal of Oriental Neuropsychiatry, Herbal Medicine, Current Status. Copyright 2014 by The Korean Society of Oriental Neuropsychiatry. All rights reserved. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 288 The Current Status about Alzheimer s Dementia in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine I. 서론 1970년에창립된대한한방신경정신과학회는한의사협회산하 43개주요학회중의하나로년 4회동의신경정신과학회지를발간하고있다. 동의신경정신과학회지는 1990 년창간이후, 2007년 18권 1호부터한국연구재단 ( 구, 대한학술진흥재단 ) 에등재되었고 1), 2014 년현재까지총 25권이간행되었으며, 치매, 우울증, 수면장애등을포함하는신경정신영역의논문을다수게재하고있다. 한국표준질병사인분류 KCD-10 에의거, 알츠하이머형치매는알츠하이머병에서의치매, 조기발병알츠하이머병에서의치매, 만기발병알츠하이머병에서의치매, 비정형또는혼합형의알츠하이머병에서의치매, 상세불명의알츠하이머병에서의치매등으로분류된다 2). 근거중심의학 (Evidence Based Medicine) 은최신의연구결과를바탕으로피시술자에게가장적합한치료방법을선택하여시술하는것으로 1991 년캐나다임상역학자 Guyatt 에의해등장한이후로, 전세계적으로중요성이높아지고있는데, 우리나라에는 1997 년 S. Richard 의강연에의해소개된후 3) 각종연구가진행되고있으며관련논문도발간되고있다. 한의학계에서도이와같은흐름에발맞추려는노력이진행되고있다 4-6). 논자는한방신경정신과영역에서의알츠하이머형치매연구현황을확인하고, 현행의연구결과물을 EBM 기준에의거하여살펴보고, 향후의치매관련연구와임상의지향방향을찾아보고자, 한방신경정신과학회지에발표된알츠하이머형치매관련연구현황을세밀히분석하여, 4가지분야로나누어정리한후다소의지견을얻어보고하는바이다. II. 연구대상및방법 1. 연구대상및방법 1990 년창간호부터 2014 년 25권 2호까지간행된동의신경정신과학회지를대상으로하였다. 검색가능한논문중 알츠하이머형치매, 알츠하이머병 을키워드로하는논문을우선수집하고, 2차로 323편의논문내용을하나씩확인하면서알츠하이머형치매와관련 된연구총 46편을확인하였다. 확인한논문을실험적연구, 단일혹은소수증례보고, 다중증례분석연구, 임상시험의 4가지분야로나누어세부정리하였다. III. 결과 1. 알츠하이머형치매관련논문의전체적현황 1990년부터 1996년까지동의신경정신과학회지에서알츠하이머형치매관련논문은보고되지않았으며, 1997 년부터매년 1~7편정도가수록되었다. 총 46편의논문중 40편이실험연구로대부분을차지했으며, 그외 4편의임상연구, 1편의소수증례보고, 1편의다중증례분석연구가나타났다 (Table 1). 2. 알츠하이머형치매관련실험연구 알츠하이머형치매와관련한실험연구는총 40편이보고되었다. 그중한약처방을이용한실험연구는 27편, 단미 ( 單味 ) 를이용한실험연구는 12편, 그리고약침을이용한실험연구는 1편이었다. 실험연구에서이용된총명탕가미방, 천왕보심단, 형방사백산, 독활지황탕, 가미보양환오탕등이대표적이었으며, 이 Table 1. The Articles about AD in Journal of Oriental Neuropsychiatry ES CS CDA CT TOTAL TOTAL ES: Experimental Study, CS: Case Study, CDA: Clinical Data-Analysis, CT: Clinical Trial AD: Alzheimer Dementia.

3 TY Kim, CJ Kum, JW Oh 289 Table 2. The Articles about Experimental Study of AD in Journal of Oriental Neuropsychiatry Data (N) Remarks Experiment using herbal medicine Species including InSamYangYoung-tang (Renshenyangrongtang) Experiment using herbs Species including Gastrodia elata Blume (GEB) Experiment using herbal-acupuncture solution 1 Hominis Placenta Herbal-Acupuncture Solution AD: Alzheimer Dementia. 용된본초의종류에는천마, 모과, 산사육, 목근피, 상산등이있었다. 약침을이용한실험연구에는자하거약침이이용되었다 (Table 2). 총 40편의실험논문중 2010년부터 2014년까지의기간에보고되어최근의연구동향을반영하고있는논문은총 8편이었다 (Table 3). In vitro에서 β-site amyloid precursor proteincleaving enzyme 활성과 β-amyloid protein 생산에대한총명탕가미방 ( 聰明湯加味方 ) 의효과에서는 BV2 세포주에다양한조합의총명탕가미방 ( 聰明湯加味方 ) CmTP-C1 10 의추출물을가하고 LPS와 β-amyloid(βa) 처리를하여 APP, BACE 의유전자발현과효소활성, βa의생산에대해실험적으로관찰한결과 CmTP-C 9 총명탕 ( 聰明湯 ) 조합추출물은APP mrna 와 BACE2 mrna 유전자발현을가장크게억제하였고, βa의생산과 BACE 효소활성을억제하는결과를얻었다 7). βa로유도된 Alzheimer's Disease 동물모델에대한형방사백산 ( 荊防瀉白散 ) 의효과논문에서는형방사백산 ( 荊防瀉白散 ) 추출물로 LPS+βA 를처리한 BV2 미세아교세포주에서 IL-1β, IL-6, TNF-α 및 NOS-II mrna 발현억제및스코폴라민으로유도된기억소실생쥐의행동변화에대한형방사백산 ( 荊防瀉白散 ) 추출물효과를실험하였다. 그결과형방사백산 ( 荊防瀉白散 ) 추출물은 LPS+βA 를처리한 BV2 미세아교세포주에서 IL-1β, IL-6, TNF-α 및 NOS-II mrna 발현을억제하였고, βa 단백질생성을억제하였다. 그외형방사백산 ( 荊防瀉白散 ) 추출물은기억력개선효과를보였으며, AD 병변뇌조직에서세포내 IL-1β 단백질과 TNF-α 단백질의과발현을억제하였고, AD 병변뇌조직의허혈상태를개선하였고, 허혈로인한뇌조직손상을억제하였다. 또한 AD 병변뇌조직에서 tau 단백질과 GFAP 발현을억제하였다 8). 독활지황탕 ( 獨活地黃湯 ) 이 βa로유도된 Alzheimer's Disease 병태모델에미치는영향에관한논문에서는독활지황탕 ( 獨活地黃湯 ) 추출물이 BV2 microglial cell line에서 IL-1β, IL-6, TNF-α 및 NOS-II mrna, 및 BACE, APP 염증유전자발현을억제하고 Morris water maze를통한 step-through latency, distance movement-through latency 측정에서유의성있는기억력개선효과를나타냈다 9). 인삼양영탕 ( 人蔘養榮湯 ) 이 βa를처리한 PC12 세포와생쥐의손상뇌신경조직에미치는영향에관한논문에서는인삼양영탕 ( 人蔘養榮湯 ) 이 βa를처리한 PC12세포와생쥐해마조직의 dentate gyrus 부위의 hilus 부위, CA3, CA1 pyramidal cell 층및생쥐대뇌피질의신경세포에서세포의생존율을향상시켰고, 세포의형태를정상세포와유사하게회복시켰다. 또한세포의자멸유도단백질인 caspase 3의생성수준을억제시켰으며, 세포의생존에관여하는단백질인 phospho-erk1/2 의생선수준을증가시켰다. 그리고인삼양영탕의손상신경세포에대한효과는양성대조군으로이용된 galantamine 처리군과유사한양상을나타냈다 10). 뇌해마배양조직을이용한치매뇌손상모델에대한소풍순기원 ( 疏風順氣元 ) 과황련해독탕 ( 黃連解毒湯 ) 처방약재의신경보호효과연구에서는기관형적해마절편배양에서황련해독탕 ( 黃連解毒湯 ), 소풍순기원 ( 疏風順氣元 ) 및처방구성약물을처리하여 βa로유발한치매성뇌세포손상에대한보호효과를살펴본결과황련해독탕 ( 黃連解毒湯 ) 과소풍순기원 ( 疏風順氣元 ) 각각의처방을함께처리하였을때 72시간에서단독처리한군보다소풍순기원 ( 疏風順氣元 ) 이통계적으로유의하게세포사멸이적은것으로나타났으며황련해독탕 ( 黃連解毒湯 ) 의처방구성인황금 ( 黃芩 ), 황련 ( 黃連 ), 황백 ( 黃柏 ), 치자 ( 梔子 ) 와소풍순기원 ( 疏風順氣元 ) 의처방구성인대황 ( 大黃 ), 차전자 ( 車前子 ), 욱리인 ( 郁李仁 ), 빈랑 ( 檳榔 ), 마자인 ( 麻子仁 ), 토사자 ( 兎絲子 ), 우슬 ( 牛膝 ), 산약 ( 山藥 ), 산수유 ( 山茱萸 ), 지각 ( 枳殼 ), 독활 ( 獨活 ) 과 βa 을함께처리하였을때 72시간에서 βa 를단독처리한군보다빈랑 ( 檳榔 ), 산

4 290 The Current Status about Alzheimer s Dementia in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine Table 3. Recent Experimental Studies about AD in Journal of Oriental Neuro psychiatry (2010~2014) Experimental study Publish Herb med Type Methods Conclusion Effect of Chongmyung-Tang Prescription Combination on the Production of Amyloid β protein and β-site amyloid precursor protein-cleaving enzyme Activity in vitro The Effects of HyungBangSaBaek-San (JingFangXie- BaiSan) on the Alzheimer's Disease Model Induced by βa The Effects of Dokhwaljihwang-tang (Duhuodihuangtang) on the Alzheimer's Disease Model Induced by βa The Neuroprotective Effects of InSamYangYoung-tang on Aβ-induced Damages in Mice Investigation of Neuroprotective Effect Using Herb Medicine against Dementia related Brain Damage in Organotypic Hippocampal Slice Culture Protective Effect of Gastrodia Elata on Neuronal Cell Damage in Alzheimer's Disease Up-and-Down Procedure (UDP) Determinations of Acute Oral Toxicity of LMK02-Jangwonhwan in SD Rats The Effects of Jeoreongchajeonja-tang (Zhulingjuqianzitang) on the βa and LPS Induced BV2 microglial cell 2010 Chongmyung -Tang 2010 HyungBangSa Baek-San (JingFangXi ebaisan) 2010 Dokhwaljihwang-tang (Duhuodihua ngtang) 2010 InSamYang Young-tang 2010 Hwangryeonh aedoktang, Sopung soongiwon 2010 Gastrodia elata Blume (GEB) 2010 Jangwonhwan (LMK02) 2012 Jeoreongcha jeonja-tang (Zhulingjuqianzi-tang) in vitro The effect of CmTP-C1-10 extract on expression of APP mrna. BACE2 mrna in BV2 microglia cell line treated by lipopolysacchride (LPS) and amyloid beta protein fragment were investigated. in vivo The effects of the HBSBS extract suppressed the expression of IL-1β, IL-6, TNF-α and NOS-II mrna in BV2 microglial cell line treated with LPS plus βa were investigated. The effects of the HBSBS extract on the behavior of the memory deficit mice induced by scopolamine were investigated. in vitro The effects of the DHJHT extract on the pro inflammation cytokines mrna expression and production of BACE APP and βa in in BV2 microglialcell inetreated by lipopolysacchaide LPS) plus βa were investigated. The effects of the DHJHT extract on the behavior of the memory deficit mice induced by scopolamin e were investigated. in vitro The effects of the InSamYangYoung-tang (Renshenyangrongtang) extract on neural damag es of cultured PC12cells and hippocampal and cortical neurons induced by βa were investigated. in vitro We induced dementia related brain damage in organo typic hippocampal slices by βa. Those slices were treated with 2 herb medicines. Using by PI stain in g, the extents of cell death were assessed. After that, we selecte d the best effective on e among those herb medicines and the major components of that medicine were studied to reveal neuro protective effec ts and related protein s by in PI stating. in vitro As a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with β-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. After β-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. in vivo Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3. The toxicity of LMK02 was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats. 3 female rats received 5,000 mg/10 ml/kg of test substance and their death rate, clinical sings, weight changes and autopsy findings had been observed for 2 weeks. in vitro / in vivo The effects of the JCT extract on IL-1β, IL-6, TNF-α, COX-2, NOS-II mrna, APP mrna, BACE mrna, Nitric oxide (NO), and βa protein production in the BV2 microglia cell lines treated with LPS and βa were investigated. CmTP-N is effective for therapy and prevention of AD. HyungBangSaBaek-San (JingFang- XieBaiSan) can be considered as the medi cine for AD therapy. DHJHT is effective for AD therapy. InSamYangYoung-tangcan affect the rehablization of cell neural cel l damage in AD-related brain tissue. Sopungsoongiwon is more effective medicine than Hwangryeonhaedoktang in terms of protecting cells from brain damage. GEB is effective to prevent apoptosis of brain cells and can be used in prevention and therapy of AD. No specific symptoms or death were resulted in this experiment. No significant changes in rats weight. No significant differences in atopsy. JCT is effective for AD therapy and can be considered for future medicine of AD. AD: Alzheimer Dementia.

5 TY Kim, CJ Kum, JW Oh 291 수유 ( 山茱萸 ), 지각 ( 枳殼 ), 차전자 ( 車前子 ), 독활 ( 獨活 ) 은통계적으로유의하게세포사멸이적은결과를나타냈다 11). 치매병태모델에서천마 ( 天麻 ) 의신경세포손상보호효과에관한논문에서는신경세포독성실험에널리활용되고있는 SH-SY5Y 세포주에사용하여, βa를처리하였더니아포토시스가진행되었는데, 천마 ( 天麻,GEB) 추출물전처리로아포토시스가효과적으로감소되었다. GEB 의항산화효능을관찰하기위해과산화수소로세포독성을유발한경우, GEB 추출물전처리로보호효과가나타났다. SNAP 를처리한경우과산화질소생성이증가되었고, βa를처리한경우 inos 발현이증가되었는데, 이는모두 GEB 추출물에의해억제되었다. GEB 항산화보호효과의메커니즘을알아내기위해세포내항산화효소의발현을 RT-PCR 로관찰한결과, heme oxygenase-1, GAPDH 및 1-glutamate cysteine ligase 의발현이증가되었다. 또한 GEB 추출물은스코폴라민으로유도된기억력손상에대하여보호효과를가졌다 12). Sprague-Dawley 랫트를이용한 Up & Down 법 (UDP) 에의한 LMK02 의단회경구투여독성시험에관한논문에서는장원환 (LMK02) 독성시험을위해 6주령 Sprague- Dawley 랫트 (specific pathogen free: SPF) 를사용하였다. 5,000 mg/10 ml/kg 을투여한후 14일동안사망률, 이상증상및체중변화를측정하고, 그후 Sprague-Dawley 랫트를희생하여부검소견을관찰하였다. 그결과실험기간동안사망동물이나이상증상및체중변화가관찰되지않았으며, 이상소견이관찰되지않았다 13). 저령차전자탕 ( 豬苓車前子湯 ) 이 βa와 LPS 로처리된 BV2 microglial cell에미치는영향에대한논문에서는 LPS와 βa 를처리한 BV2 microglial cell 에서저령차전자탕 ( 豬苓車前子湯 ) 추출물이 IL-β, IL-6, TNF-α, COX-2, NOS-II mrna, APP mrna, BACE mrna, 산화질소 (nitric oxide:no) 및단백질생성에미치는영향을조사하였다. 실험결과, 저령차전자탕 ( 豬苓車前子湯 ) 추출물은 IL-β, IL-6, TNF-α, COX-2 및 NOS-II mrna, BACE, APP mrna 의발현을억제하였으며, NO 와단백질생성의발현을억제하였다 14). 3. 알츠하이머형소수증례보고소수증례에대한보고는총 1편이며, Alzheimer 형치매환자 2례에대한임상적고찰논문이다 16). 이논문에서는침구치료와한약치료, 뜸, 사혈요법, 향기요법, 미소팩, 레이저치료등을이용하여치료하였다. 침구치료시체침과이침, 그리고구법을사용하였으며특정부위의경혈에사혈요법도이용하였다. 한약치료는사물안신탕, 안신청뇌탕, 귀원탕, 익기도담탕등의처방이활용되었다. 치료효과는 MMSE-K 진단도구를이용해측정되었다. 약 2개월의치료결과 MMSE-K 점수상유의할만한변화를얻지못했으나증상의측면에있어서는뚜렷한호전을보였다 (Table 4). 4. 알츠하이머형치매관련다수증례분석연구다수증례분석보고는총 1편이며 Dementia of Alzheimer Type 에관한한의학적임상연구이다. 이논문에서는 CT, MRI, SPECT 의검사소견이나임상적으로 DSM-IV의기준에부합하는환자 45명을대상으로사상체질을분석하여이에합당한사상체질별약물치료및침치료를진행하였다. 침치료는사상체질에바탕을둔태극침법을활용하였고, 약물치료로는체질감별진단을거친후태음인에게조위승청탕과우황청심원, 소음인에게향부자팔물탕과사향소합원, 소양인에게는형방지황탕을각각복용토록하였다. 치료를받은후에는각각의환자들에게기억력, 지남력, 기명력, 주의및계산, 언어및구성능력을기준으로치료효과를판단한결과치료효과에서 45명의환 Table 4. The Case Studies about AD in Journal of Oriental Neuropsychiatry Case Clinical case study of 2 AD patients Publsh 1997 N 2 A-Tx. & Acupoint Chung-kyung Acupuncture Method, Auricular acupuncture, and Cha-rak Acupuncture Method H-med Samuransin-tang, Anshinchungneo-tang, Gwiwon-tang, Ikgidodam-tang Tools MMSE-K Remarks Aroma therapy (rosemary, rosewood, peppermint) AD: Alzheimer Dementia.

6 292 The Current Status about Alzheimer s Dementia in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine Table 5. The Clinical Data-Analysis about AD in Journal of Oriental Neuropsychiatry Clinical Data-Analysis A Clinical study on the effects of oriental medical treatment on Dementia of Alzheimer type Publsh 1998 Case (N) 45 A-Tx. & Acupoint Acupuctural treatment based on Sasang constitutions (Taegeuk). Herb-med Herbal treatment based on Sasang constitutions. Tools Assessed by criteria for memory, orientation, registration, attention and calculation, language. Remarks Sasang constitutions AD: Alzheimer Dementia. Table 6. The Clinical Trials about AD in Journal of Oriental Neuropsychiatry Clinical Trials Type Publish Herbal medicine Tools Remarks A Study of Gongjin-dan in patients with mild Dementia of Alzheimer type CT 2004 Gongjin-dan K-DRS Evaluation f/u after 100 days The effects on Jowiseungchungtang of patients with CT 2003 Jowiseungchung-tang auditory ERP, Evaluation f/u after 9 months early DAT using auditory ERP and K-DRS K-DRS The effects on Kunneotang of Patients with Early Dementia of Alzheimer Type - 12 Months Clinical Study - CT 2005 Kunneo-tang MMSE-K, K-DRS, Evaluation f/u after 12 months ERP A Study of Jowiseungchungtang in patients with mild CT 2003 Jowiseungchung-tang K-DRS Evaluation f/u after 6 months Dementia of Alzheimer type AD: Alzheimer Dementia, CT: Clinical Trial. 자중상당호전 14명, 다소호전 13명, 별무변화 16명, 악화 2명으로호전된양상이 60% 를차지하였다 (Table 5) 17). 5. 알츠하이머형치매관련임상시험연구총 4편의임상시험이보고되었는데, 각한방처방이알츠하이머형치매환자에미치는영향을다룬내용이주를이루었다. 연구에사용된처방은공진단, 조위승청탕, 건뇌탕이었다 (Table 6). 공진단이알츠하이머형치매환자에게미치는영향에관한논문에서는치료공고를통하여모집된알츠하이머형치매환자 33명을대상으로 100 일간공진단을매일저녁수면전에하루 1환씩복용케하여 100일이지난후 K-DRS 척도의변화정도를측정한결과 100일간의공진단투여가치매환자의인지기능을향상시킴을알수있었다 18). 알츠하이머형치매환자에대한조위승청탕 ( 調胃升淸湯 ) 의효능-청각 ERP 및 K-DRS 의성적변화를통하여-에관한논문에서는초기 DAT 환자 15명과정상노인 10명을대상으로 K-DRS 와청각 ERP 를시행하고 DAT 환자집단에 게 9개월간조위승청탕을복용토록한후검사를다시실시하여양집단간의차이를관찰한결과, 조위승청탕이초기 DAT 환자들에게있어인지기능의저하를방지할수있는효과가있음을규명하였다 19). 초기알츠하이머형치매환자에대한건뇌탕의효능-12 개월임상연구-에관한논문에서는외래에내원한환자중초기 DAT 환자의진단기준및조건에부합하는환자 22명을대상으로 12개월간건뇌탕을투여하고 MMSE-K, K-DRS 및 ERP 를시행한결과, 건뇌탕이초기 DAT 환자들에게있어인지기능의저하를방지할수있는효과가있다고밝혔다 20). 조위승청탕이초기 Dementia of Alzheimer type 환자의인지기능변화에미치는효과에관한논문에서는 DAT 로진단받고외래로내원한초기치매환자 31명을대상으로 6개월간조위승청탕을일일 4회복용시킨결과, 조위승청탕의복용이치매환자의인지기능장애의진행을막아준다는것을알수있으며, 나아가치매예방효과에대한가능성을제시하였다 21).

7 TY Kim, CJ Kum, JW Oh 293 IV. 고찰 치매는뇌의만성적진행성변성질환에의해흔히기억장애및기타지적기능의상실이일어나는임상증후군을말한다 22). 좀더넓은의미로는지적황폐화뿐아니라행동이상및인격변화를초래하며, 정서적기능상실과진행성인지적황폐화가사회적혹은직업적기능의장애를초래하게되는상태로, 크게알츠하이머형치매와혈관성치매의두가지로구분되고있다 23,24). 알츠하이머병 (Alzheimer's disease: AD) 은퇴행성치매의대부분을차지하는신경정신질환으로중추신경계피질이나대뇌기저핵혹은시상등을포함한피질하구조물에일시적, 영구적인손상이발생함으로써사회적기능이나직업활동및일상생활유지중에현저한곤란을초래할정도의주요신경인지기능장애증상과다양한행동및정신증상을동반하는질병군을말하며 25-27) 노인성치매와함께알츠하이머형치매 (Dementia of Alzheimer type: DAT) 로불린다 28). 최근건강보험심사평가원이 년까지의 알츠하이머병에서의치매 (F00) 에대해분석보고한자료에따르면, 진료인원은 2009년 106,474명에서 2013년 238,882명으로 5년간약 13만명이증가 (124.3%) 하였고, 연평균증가율은 22.4% 로나타났으며, 총진료비는 2009년약 2511억원에서 2013 년약 7046 억원으로 5년간약 5,000 억원이증가 (180.6%) 하였고, 연평균증가율은 29.5% 로나타났다 29). 알츠하이머형치매는한국질병사인분류 KCD-10 에의거하여알츠하이머병에서의치매, 조기발병알츠하이머병에서의치매, 만기발병알츠하이머병에서의치매, 비정형또는혼합형의알츠하이머병에서의치매, 상세불명의알츠하이머병에서의치매등의종류를포함하고있다 30). 알츠하이머형치매와관련된연구가다양한학회를중심으로이루어지고있는데, 우리나라에는대한치매학회 Korean Dementia Association, 고령자치매작업치료학회 Society of occupational therapy for the aged and dementia, 대한신경과학회 Korean Neurological Association 등이있다. 한의학계에서는치매관련학회는아직결성되지않았으나대한한의사협회산하의한방신경정신과학회, 한방내과학회등을통하여연구논문들이발표되고있다. 대한한방신경정신과학회는 1970년대에결성된이후꾸준한학술활동이있었고, 1990년도부터정기학술지 < 동의 신경정신과학회지 > 간행을시작하였으며, 2007년 < 동의신경정신과학회지 > 는대한학술진흥재단의공식등재지로수록되었으며, 현재까지 25권이발간되며수면장애, 치매, 우울증등의전문영역에대한논문을다수게재하고있다 31). 검색결과총 47편의알츠하이머형치매관련논문을검토하였고, 1990년부터 1996년까지동의신경정신과학회지에서알츠하이머형치매관련논문은보고되지않았으며, 1997 년부터매년 1 7 편정도가수록되었다. 총 47편의논문중 41편의실험연구논문이대부분을차지했으며, 실험연구논문은크게한방처방을이용한실험연구, 단미 ( 單味 ) 를이용한실험연구, 그리고약침을이용한실험연구로분류할수있었다. 그외 4편의임상연구는공진단, 조위승청탕, 건뇌탕등의처방을이용하여알츠하이머형치매환자에미치는영향을고찰하는형식으로이루어졌고, 1편의소수증례보고, 1편의다중증례분석연구또한찾아볼수있었다. 연구에서주로사용된평가도구중 MMSE-K 는간이정신상태검사 (MMSE: Mini-Mental State Examination) 32) 를한국노인들에게이용될수있도록한국어로번안하고수정하여개발된것으로, 시간및장소에대한지남력 ( 각 5점 ), 기억등록 (3점), 언어기능 (7점), 이해력및판단 ( 각 1점 ) 등의소척도로구성되어있으며, 교육유무에따라무학자의경우시간에대한지남력 1점, 주의집중및계산에 2점, 언어기능에 1점씩가산하되각항목에서만점을초과하지않도록교정되며최고점수는 30점이다 33). K-DRS 는국내치매환자를진단하기위해서 Mattis 의 Dementia rating scale 34) 을한국에서재표준화한것으로검사의타당도는각규준집단별로 이고검사- 재검사신뢰도는 0.96이다 35). K-DRS 를이용하여치매환자의진단에중요한인지기능들을 5개의소검사로측정하였다. 각소검사는주의 (attention) 는 8개, 관리기능 (initiation & preservation) 은 11개, 구성 (construction) 은 6개, 개념화 (conceptualization) 는 6개, 기억 (memory) 은 5개로써, 모두 36개의과제로구성되어있다 36). 알츠하이머형치매관련임상시험연구결과들을검토함에있어, 연구의질에관한평가또한추가적으로이루어져야할것으로사료된다. 현재연구된방법과같이일정기간후각 scale의개선정도를 evaluation 하는데그치지않고 JADAD scale 등을활용하여연구된결과의 quality 를평가

8 294 The Current Status about Alzheimer s Dementia in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine 하여제시하는것이요구되는바이다. JADAD scale 은옥스퍼드질점수시스템으로도알려져있으며, 무작위배정비교임상시험의방법론적질을독립적으로평가하는방법이다 37). 뇌파와동일한방법으로측정되는 ERP는자발적으로일어나는전기활동인뇌파와는달리, 자극혹은사상 (event) 의제시와관련되어일정시간동안나타나는뇌의전기적인활동으로, 제시된자극이나사상에대한반응으로나타나는전기적활동을의미한다. 인지과정의결과만을측정하는행동적평가와는달리 ERP 는인지과정이진행되고있는동안에뇌의전기적활동을측정하기때문에행동적평가보다는더직접적으로인지작용을연구할수있다는장점이있으며이러한이유때문에 ERP 는기억, 언어, 학습및정서등인지심리학의여러분야에서사용되고있다 38-40). 대부분의임상연구는 P300 ERP 를발생시키기위하여청각자극을사용하고있다. 청각자극은상대적으로쉽게만들수있고과다한눈동자의움직임이포함되는뇌파가아닌가공물에의존하지않고지속적으로피험자의주의집중을모을수있기때문에 P300 현상에관한대부분의기초자료를수집하는데이용되어왔다 41). 치매의치료에대한과거의문헌자료를종합하면감정적원인으로인해담 ( 痰 ) 이생겨나타난심 ( 心 ) 및간담 ( 肝膽 ) 의장부생리의이상과소아선천부족 ( 先天不足 ) 이나노년허쇠 ( 老年虛衰 ) 로인한뇌수 ( 腦髓 ) 의공허 ( 空虛 ) 가치매의유발요인으로보았으며, 여기가위기 ( 胃氣 ) 원기 ( 元氣 ) 의강약 ( 强弱 ) 이병의진퇴 ( 進退 ) 를결정하는것으로보았고, 그에따른치법으로는거담 ( 去痰 ), 보심비 ( 補心脾 ), 개울축수 ( 開鬱逐水 ), 건위통기 ( 建胃通氣 ) 등을소개하고있다 41). 이러한치료원리에근거하여최근의치료에서는각각약물요법으로서총명탕, 천왕보심단, 형방사백산, 독활지황탕, 가미보양환오탕, 고진음자, 사향소합원, 인삼양영탕, 소풍순기원, 익정지황탕, 건뇌탕, 녹용대보탕, 조기해어탕, 칠복음가미방, 향부자팔물탕, 저령차전자탕을활용하고, 침구요법으로서백회, 신정, 인당, 인중, 합곡, 태충등의혈위를선용하는체침과이침등을활용하고있다. 약침요법은침구요법과약물요법을결합한신침요법의일종이다. 중국에서는 1950년경에마취제를경혈에주입하여통증성질환을치료하는 공혈봉폐요법 ( 孔穴封閉療法 ) 이일부병증에유효하다는보고가이루어진후연구가활성화되었으며, 현재는 수침요법 ( 水鍼療法 ), 공혈주사요법 ( 穴位注射療法 ) 이라고불리고있다 42). 약침치료는고전적한방치료에서는찾아볼수없는특수한치료법이며현재까지의임상연구및치험례의수가부족하므로앞으로연구가활발하게이루어져야할것이라고생각된다. 알츠하이머형치매를치료하는데있어서도실험연구에서자하거약침이채택된예가있을뿐임상적으로약침요법이알츠하이머형치매를치료하는데있어미치는영향등에대해거의연구결과가없어앞으로의추가연구가요구된다. 알츠하이머형치매치료를위해추가적으로사용된치료법은향기요법 ( 香氣療法 ) 및 He-Ne Laser 치료법등의방법이있었다. 상기치료법들은치매의기질적인원인을해소하기보다는증상개선에도움이되는보조요법으로시행된것으로보이며, 이들이임상에활용됨으로써고전적한방치료의범주를확장시켰다는점에서주목할만하다. 전체적으로한방신경정신과학회지에게재된알츠하이머형치매관련보고는대부분실험연구에치중되어있었으며한의학임상에서사용되어지는다양한치료방법들의효과에대해서는연구된바가적었다. 따라서근거중심의학의관점에서보았을때근거의수준은대개약한편이었으며, 현재까지의자료를토대로하여체계적리뷰나메타분석과같은 2차문헌이나오기는어려울것이라고판단된다. 이를보강하기위해서는지금까지시행되지않은문헌연구나, 다중증례분석연구, 증례보고연구, 리뷰연구등의자료가더많이필요할것으로사료되는바이다. V. 결론 1990 년부터 2014 년까지발간된동의신경정신과학회지 25권에수록된논문중알츠하이머형치매관련논문을검색하여다음과같은결론을얻었다. 1. 동의신경정신과학회지의총 47편의알츠하이머형치매관련논문을찾았으며, 41편의실험연구, 1편의소수증례보고, 1편의다중증례분석연구, 4편의임상시험연구가있었다 년부터 1996 년까지한방신경정신과학회지에서알츠하이머형치매관련보고는나타나지않았으며, 그후매년 1 7 건정도보고되고있는추세이며, 발표된대부분의논문은실험연구논문이었다. 3. 알츠하이머형치매의침구치료에는백회, 신정, 인당,

9 TY Kim, CJ Kum, JW Oh 295 인중, 합곡, 태충, 후계, 임읍등의혈자리 ( 정경침법 ) 가사용되었으며, 이침또한활용되었다. 그외사혈요법 ( 자락침법혹은자락요법 ) 등을이용한예도있었다. 4. 알츠하이머형치매의치료에이용된한방처방에는공진단, 조위승청탕, 건뇌탕, 향부자팔물탕, 사향소합원, 형방지황탕등이있었으며, 이는실험연구에서이용된다수의처방들과같거나비슷한방의를가진경우가많았다. 5. 알츠하이머형치매의임상치료에는약침이사용된예가보고되지않았으며, 관련실험연구에서는자하거약침을이용하여연구가진행된예가있었다. 6. 알츠하이머형치매의진단과치료효과검증에사용되는정량적도구로는 K-DRS 와 MMSE-K 가주로사용되었다. REFERENCES 1. Jung JH, Ha JW, Kim BK, The Current Status about Sleep Disorder in the Journal of Oriental Neuropsychiatry for Evidence Based Medicine, Journal of Oriental Neuro psychiatry. 2012;23(4); Park JY. A study on Introducing of Evidence-Based Medicine(EBM) Information Services:Based on the Clinical residents' Information Seeking Behavior and the Perception of EBM. Department of Library & Information Science 4. Jim JH, Lee JK, Shin HK Analysis of studies on Bojungikgitang (BuZhong yiqi-tang) to establish the fundament for Evidence Based medicine (EBM):Korea Journal of Oriental Medi cine. 2011;17(2): Kim JH, Lee JK, Ha HK, Seo CS, Lee MY, Lee HY, lee DY, Jung DY, Lee NH, Lee JA, Huang DS, Shin HK. Analysis of studies on Guibi-tang (Guipitang) for Fundamental Establishment of Evidence Based Medicine(EBM). Journal of Oriental Neuropsychiatry. 2009;20(3); Baek SM, Lee SH, Kim JE, Liu Y, Park HJ, Kim BY, Choi SM. Traditional Korean Medicine Practitioners' Awareness and Attitudes toward Evidence Based Medicine. Korean Journal of Acupuncture. 2011;28(3); Lim JH, Jung IC, Lim JS, Lee SY. Effect of Chongmyung - Tang Prescription Combination on the Production of Amyloid β protein and β-site amyloid precursor protein - cleaving enzyme Activity in vitro. Journal of Oriental Neuropsychiatry. 2010;21(2); Yoon JC, Lee SR, Jung IC. The Effects of HyungBang- SaBaek-San (Jing FangXieBaiSan) on the Alzheimer's Di sease Model Induced by βa. Medicine of Oriental Neuropsychiatry, 2010;21(2); Jeon MY, Lee SR. The Effects of Dokhwaljihwang-tang (Duhuodihuangtang ) on the Alzheimer's Disease Model Induced by βa. Journal of Oriental Neuropsychiatry. 2010;21(1); Jang YJ, Jung IC, Lee SR. The Neuroprotective Effects of InSamYang Young-tang(Renshenyangrongtang) on Aβ -induced Damages in Mice, Journal of Oriental Neuropsychiatry. 2010;21(1); Chu CN, Kim JW, Chung SY, Park JH. Investigation of Neuroprotective Effect Using Herb Medicine against Dementia related Brain Damage in Or ganotypic Hippocampal Slice Culture, Journal of Oriental Neuropsychiatry. 2010;21(1); Jung YS, Kang JH, Park SH, Kwon YM, Kim GW, Koo BS. Protective Effect of Gastrodia Elata on Neuronal Cell Damage in Alzheimer's Disease. Journal of Oriental Neuropsychiatry. 2010;21(2); Kang HW, Kwon YM, Lee SW, Kim JH, Lee HG, Jang HH, Park BR, Lyu YS. Up-and-DownProcedure(UDP)Deter minations of Acute Oral Toxicity of LMK02-Jangwonhwan in SD Rats. Jour nal of Oriental Neuropsychiatry. 2010; 21(3); Ryu CH, Jung IC, Lee SR. The Effects of Jeoreongchajeonja-tang (Zhu lingjuqianzi-tang) on the βa and LPS Induced BV2 microglial cell, Journal of Oriental Neuropsychiatry. 2012;23(1); Park DM, Lee SR, Lim JS, Kim SH, Jung IC. A Thirteen Week Repeated Oral Dose Toxicity Test and A Four Week Recovery Test of ACM(Added Chongmyung-tang) in Sprague-Dawley Rats, Journal of Oriental Neuropsychiatry. 2012;23(3); Kim BG, Jung IC, Lee SR, Kim WJ. Clinical Study of Two Patients With Dementia of Alzheimer's Type. 1997;8(2); Kim BG, Hyun KC, Kim JW, Whang WW. A Clinical Study on the Effects of Oriental Medical Treatment on Dementia of Alzheimer type, Journal of Oriental Neuropsychiatry. 1998;9(1); Jung HC, Jang HJ, Sung WY, Lee SH, Son JH, Han SH. A study for Gongin-dan in patients with mild dementia of Alzheimer type, Journal of Oriental Neuropsychiatry. 2004;15(2); Kim BG, Kim JW, Kim HT, Jung KC, Whang WW. The effects of Jowiseungchungtang of patients with early DAT using auditory ERP and K-DRS. Journal of Oriental Neuro psychiatry. 2003;14(2); Eom HJ, Kim JW, Park EH, Kim HT, Whang WW. The Effects on Kunneotang of Patients with Early Dementia of Alzheimer Type - 12 Months Clinical Study-. Journal of Oriental Neuropsychiatry. 2005;16(1); Cho SH, Kim JW, Kim HT, Chung KC, Whang WW. A Study of Jowiseungchungtang in patients with mild Dementia of Alzheimer type. Journal of Oriental Neuropsychiatry. 2003;14(1); Na DR. Clinical Appraoch of Dementia. Journal of Korean Medical Association. 2002;45(4);361-7.

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