Dementia and Neurocognitive Disorders 2009; 8: 1-14 REVIEW 치매와실서증 윤지혜 *, 나덕렬 * 김향희, 성균관대학교의과대학삼성서울병원신경과 * 연세대학교대학원언어병리학협동과정 연세대학교의과대학재활의학교실 Received : February 4, 2009 Revision received : February 6, 2009 Accepted : April 20, 2009 Address for correspondence HyangHee Kim, Ph.D. Graduate Program in Speech and Language Pathology, Rehabilitation Hospital, Yonsei University College of Medicine, 250 Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-3900 Fax: +82-2-2227-7578 E-mail: h.kim@yonsei.ac.kr Agraphia in Dementia Ji Hye Yoon, M.S.*,, Duk L. Na, M.D., Ph.D.*, HyangHee Kim, Ph.D., Department of Neurology*, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Graduate Program in Speech & Language Pathology, Yonsei University, Seoul; Department of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea Agraphia can be characterized as spelling errors (as in e.g., lexical agraphia, phonological agraphia) and motoric-writing impairment. In dementia with Alzheimer s disease (AD), lexical agraphia is the prominent type of spelling errors regardless of the disease severity whereas phonological agraphia is often observed with disease progression. Motoric-writing disturbance is also common in later stage of the disease. Meanwhile, in semantic dementia, although lexical agraphia is also prominent, motoric-writing ability is usually preserved unlike AD. Other forms of dementia such as posterior cortical atrophy and vascular dementia area also reported but the specific nature of the spelling and motoric-writing deficits has not yet been explored. This article reviews the spelling and motoric-writing deficits in major types of dementia. From the review, we concluded that further research investigating on both central and peripheral components would aid us in understanding agraphic features of the various types of dementia. Key Words: Dementia, Agraphia, Spelling, Writing 서론실서증 (agraphia, ag.) 은문어 (written language) 장애의한아형으로서다양한원인질환에의해후천적으로발생한 철자및쓰기장애 를통칭한다. 이러한장애가 agraphia 로처음명명된이후로 [1, 2], dysgraphia 라는용어도함께혼용되어져왔다 [3]. Ogle는이를 amnemonic agraphia 와 apractic agraphia 로나누었으며, 전자를철자의구성이나외양에서는문제가없지만언어적으로잘못된철자를쓰는것으로, 후자를구성에서의문제로인해잘알아볼수없는 (illegible) 형태의글자를쓰는것으로설명하였다 [2]. 이후 1970년대에도래한정보처리모델 (information-processing model) 의영향으로실서증에대한연구의흐름이이전의신경해부학적인위치를밝히는것에서, 점차적으로철자와쓰기통로 (route) 상에서의장애로인한기능적인위치 (functional loci) 를찾는것으로바뀌었다. Ellis 는이러한모델에기초하여 Ogle의두가지하위유형을각각 중추실서증 (central agraphia) 과 말초실서증 (peripheral agraphia) 이라고새로이명명하였다 [4]. 이는오늘날까지널리받 아들여지고있는개념으로, 서론에서는이를좀더세분화하여살펴보고자한다. 개념적으로, 중추형이란철자체계 (spelling system) 와관련이있으며, 목표단어를산출하기위하여여러가지인지정보를사용함을의미한다. 말초형이란철자체계단계에서형성된표상 (representation) 을적절한프로그래밍을통하여손의움직임등을조절하면서실제적으로글자의형태를물리적으로산출하게되는쓰기수행과직접적인연관이있다. 이에, 본고에서는중추실서증과말초실서증을 철자 (spelling) 와 쓰기-운동 (motoricwriting) 단계의오류로각각구분하여사용하고자한다. Fig. 1 은 Roeltgen과 Heilman [5, 6] 의모델에기초하여받아쓰기단계에서철자단계와쓰기-운동단계를도식화한것이다. 먼저, 단어가쓰여지기위해서는, 중추철자단계에서크게두가지통로가필요하다. 이미장기기억 (long-term memory) 의일부로 내부철자사전 (internal spelling dictionary; internal lexicon dictionary; graphemic output lexicon) 에저장된단어 (familiar word) 의경우는, 자소와음소의불일치성 (irregularity) 이나애매성 (ambiguity) 에상관없이어휘통로 (lexical 1
2 윤지혜 나덕렬 김향희 route) 가활성화된다. 비단어 (nonword) 혹은처음들어보는단어 (unfamiliar word) 인경우에는단순히음소와대응된자소를쓰게하는음운통로 (phonological route; sublexical route; nonlexical route) 가필요하다. 또한, 어휘통로는의미 (semantic) 단계와의연관여부에따라다시어휘-의미통로 (lexicalsemantic route) 와어휘 -무의미통로 (lexical non-semantic route) 로나눌수가있는데, 전자는철자가여러가지로쓰여질수있는동음이자 (homophone) 단어를쓸때사용되는통로이며, 후자는의미체계의중재 (mediation) 없이쓰기가이루어지는통로이다 (Fig. 1). 따라서상기중추철자단계에서발생할수있는실서증은크게어휘실서증 (lexical ag.), 음운실서증 (phonological ag.), 심층실서증 (deep ag.), 의미실서증 (semantic ag.) 등 이있다. 그다음으로는자소-버퍼 (graphemic buffer) 단계즉, 중추단계를통해형성된단어가말초처리단계로가기직전에임시적으로저장되는단계가있다. 이러한단계를통해처리된일련의철자연쇄는다음의단계인이서 (allographic) 단계로가게된다. 여기서는적당한글자의형식등을결정한다. 그다음단계로는목표글자의형태를산출하기위한계획및프로그래밍 (planning and programming) 단계, 최종적으로글자를산출해내는운동집행 (motor execution) 단계등이있다. 위의여러단계중어떠한과정에손상이오는가에따라오류는다양하게나타날수가있다. Table 1은 Rapcsak 및 Beeson [7] 이제시한실서증의특징에기존연구의결과를보완하여수정한것이다. Auditory input Auditory association Heschl s gyrus 1 Semantic system 3 2 4 Auditory word engrams Wernicke s area 6 7 Orthographic system (graphemic output lexicon Nonperisylvian regions Phonological system (Phonemegrapheme conversion) Supramarginal gyrus, insula, posterior, temporal area 8 5 Graphemic buffer Lt. fronto-parietal Graphemic area (graphic motor program) Allographic store Lt. pariotooccipital Verbal output programming Broca s area Motor programming Lt. parietal lobe Graphic output programming (graphic innervatory pattern) Dorsolateral prefrontal cortex, SMA Visuospatial orientation Rt. parietal lobe Area 4 (mouth) Motor programming Area 4 (hand) Oral spelling Writing Subtypes Pathway Lexical-semantic route 1 2 3 4 5 1 2 6 5 Lexical-nonsemantic route 1 4 5 Phonological route 1 7 8 Fig. 1. Revised neuropsychological model of spelling and writing based on Roeltgen & Heilman (1985, 2003).
치매와실서증 3 정보처리모델의등장이래로, 1980년대까지는실서증에관한대부분의연구들이뇌졸중과같이선택적이고안정적인뇌병소 를가진환자들을대상으로행해져왔고, 치매와같이광범위한손상을갖는환자군에서는그이후부터점진적으로연구가시작 Table 1. Revised classification of central and peripheral agraphia based on Rapcsak & Beeson (2000) Subtypes Mechanism Distinctive features Major spelling route used Characteristics Lesion location Central Lexical Damage to Particular difficulty Phonological Phonologically Nonperisylvian graphemic output spelling irregular and plausible errors (left posterior lexicon ambiguous words (ex. circuit serkit) temporo-parietal, angular gyrus, posterior inferior temporal gyrus) Phonological Damage to Impaired nonword Lexical- Lexicalization Left perisylvian phonological route spelling semantic (ex. flig flag) (supramarginal phonologically gyrus, insula, left implausible errors posterior (ex. flig flit) temporal area) Deep Damage to all three Errors that consist of Damaged Phonological agraphia, Large spelling route real words related in lexical- semantic substitution left-hemisphere meaning to the target semantic (ex. propellar flight perisylvian word, but with little egloo eskimo) phonological or visual resemblance to the target Semantic Damaged to Special difficulty with Lexical- Homophone confusion Left hemisphere lexical-semantic homophones nonsemantic, (ex.doe dough) sites (often route phonological extrasylvian) Intermediate Graphemic Defective Errors of grapheme N/A Letter substitution, Left frontobuffer short-term storage identity and order omission, addition, parietal sites of graphemic and transposition information Peripheral Allographic Defective Inability to generate or N/A Writing impairment may Left assignment of letter select the correct be specific to case parieto-occipital shapes to abstract letter shapes in and style graphemic handwriting representation Apraxic Destruction or Poor letter formation N/A Gross errors of letter Left parietal disconnection of not attribute to morphology, spatial lobe, DLPF, graphic motor allogrphic disorder, distortion, stroke SMA damage to systems sensorimotor, cbll, or insertion and deletion, responsible for extrapyramidal illigible translating these dysfunction programs into graphic inventory pattern Spatial Inability to use Duplication or omission N/A Inability to write in a Right parietal visual, kinesthetic of letters or strokes straight line and lobe feedback to control maintain the correct the execution of spacing between writing movement letters and words Nonapraxic Dysfunction of Defective regulation of N/A Micrographia Basal ganglia, disorders of motor system movement force, cerebellum motor involved in speed and amplitude execution controlling the in handwriting kinematic parameters of writing N/A, not available; DLPF, dorsolateral prefrontal cortex; SMA, supplementary motor cortex.
4 윤지혜 나덕렬 김향희 되었다. 실서증은다양한치매의하위유형에서발생할수있는언어장애에해당되지만, 다른신경심리장애에비해서는상대적으로연구가활발하지않은실정이다. 이에, 본고에서는치매환자에서의실서증연구의현위치를파악하기위하여 1980년대이후부터최근까지보고된문헌을고찰해보고자한다. 75.7% 를차지하여가장많았으며, DLB 논문은없었다. DLB 집단을제외한각질환별연구편당평균대상자수는 AD 21.8명, FTD 7.5명, PCA 1명, VD 1명, CBD 3명, HD 12명, PSP 6명으로써편당대상자수가가장많은질환군은 AD였고, 가장적은질환군은 PCA와 VD 였다. 연구방법 1. 자료검색방법치매환자의실서증특징에대한자료를수집하기위하여다음의절차를활용하였다. 첫째, 미국의국립의학도서관의검색엔진 (www.pubmed.gov) 을이용하였다. 데이터베이스검색은 agraphia AND dementia, dysgraphia AND dementia, writing AND dementia 의검색어를통해이루어졌다. 그결과, 총 300편의연구가검색되었다. 둘째, 종합검색사이트구글 (google) 의학술검색엔진 (www.googlescholar.com) 에서 agraphia, dysgraphia, writing, dementia 의검색어를입력하여총 148편의연구를검색하였다. 이러한절차로수집된 448편의연구중에서영문으로작성된, 단어수준의받아쓰기나베껴쓰기과제를사용한실험연구만을추출한결과, 총 37 편이해당되었다. 그러나이러한기준을적용하는경우, 연구대상의대부분이알츠하이머성치매에국한되어있었으므로, 대상군간의형평성을위하여실험연구가아닌연구, 예컨대임상적인보고와같은연구도포함하였다. 상기의기준에따라총 91 편이최종분석대상으로선정되었다. 2. 질환별분류 91편의연구를대상군을기준으로하여정리해보면, 알츠하이머성치매 (Alzheimer s disease, AD) 가 37편, 전두측두엽치매 (frontotemporal lobal degeneration, FTLD) 가 24편, 후방피질위축 (posterior cortical atrophy, PCA) 이 11 편, 루이체치매 (dementia with Lewy bodies, DLB) 가 2편, 혈관치매 (vascular dementia, VD) 가 4편, 피질기저핵변성 (corticobasal degeneration, CBD) 이 8편, 헌팅턴병 (Huntington s disease, HD) 이 2편, 진행핵상마비 (progressive supranuclear palsy, PSP) 가 3편이었다. 이중에서, 실험연구 37편을기준으로정리해보면, AD 28편, FTLD 2편, PCA 2편, DLB 0편, VD 1편, CBD 2 편, HD 1편, PSP 1편이었다. 이로써 AD가총실험연구편수의 3. 과제시행방법일반적으로, 철자및쓰기 -운동장애를확인하기위한과제시행방법에는검사자가구두로제시하는자극을듣고받아쓰거나, 시각적으로제시되는단어를보고베껴쓰는것등이있다. 이와더불어, 의미기억 (semantic memory) 및사물이름쓰기 (written naming) 능력을알아보기위하여그림을보고해당되는단어를쓰게하거나, 구문구조등도확인하기위하여그림이나특정한질문에대한반응을문장수준으로쓰는방법등도있다. 그러나사물이름쓰기나서술하기 (narrative writing) 의경우, 철자및쓰기운동단계이외의의미 (semantic), 구문 (syntax), 형태 (morphology) 등과같은언어적변인도포함되므로, 결과해석시그러한변인에의한영향을배제할수없다. 또한, 서술하기의경우에는열린문맥 (open context) 으로제시되므로비정상정도를정확히측정하는것에어려움이있다. 따라서철자와쓰기 -운동능력에국한하여환자의능력을평가할수있는방법에는받아쓰기나베껴쓰기가가장적절하여, 본연구에서는이외의다른과제를사용한연구는분석시제외하였다. 4. 실험과제실험시제시되는단어과제로는, 실제단어 (real words) 범주에서는자소와음소의 1:1 대응이가능하여글자와소리가일치하는 규칙단어 (regular word, 예 ; moment), 자소와음소의대응이 1:1 대응이되지않아글자와소리가불일치하는 불규칙단어 (irregular word, 예 ; circuit) 가있다. 가상단어 (pseudoword) 의범주에서는일반적으로자소와음소의대응이일치하지만단어에의미가없는 비단어 (nonword; novel word, 예 ; trag) 가있다. 이외에연구목적에따라, 한개의단어가반드시한가지경우의자소를가지므로자소와음소의대응이 예측가능한단어 (predictable word; unambiguous words), 또는영어의각운 (rime) 에해당하거나자소는다르지만음은같은동음이자 (homophone, 예 ; buy/bye) 와같이한개의단어가한가지경우이상의자소로쓰여질수있는 예측불가한단어 (unpredictable word; ambiguous word) 로구분하여제시하기도한다.
치매와실서증 5 5. 오류유형분류 대부분의연구는중추실서증에관한결과분석시, Fig. 1에서제시된모형상에서각단계의손상과환자의오반응유형을관련지어분석하였다. 제시되는과제가실제단어에해당하는경우, 크게 2가지로나누어오반응을분석하였다. 먼저, 음운적으로적절한오류 (phonologically plausible errors, PPE; regularization) 는환자가쓴철자가정반응은아니지만목표단어 (target word) 의발음으로철자를구성하는것이고, 음운적으로도부적절한오류 (phonologically implausible errors, PIE) 는철자및발음모두에서목표단어와합치되지않는경우를말한다. 후자의경우연구자에따라이를대치 (substitution), 생략 (omission), 치환 (transposition), 첨가 (addition) 오류등으로언어학적측면에서세분화하여분류하기도하였다. 자극과제가동음이자인경우발생할수있는오류를 동음이자혼동 (homophone confusion) 이라고분류하였으며, 제시되는과제가비단어에해당하는경우에는, 발음이유사한실제단어로오반응하는것을 어휘화 (lexicalization) 라고분류하기도하였다 (Table 2). 치매유형에따른실서증연구 1. 알츠하이머성치매 (AD) 퇴행성치매의대표적인원인질환인 AD 환자의실서증은 1907년 Alzheimer에의해처음보고된이후로 [8] 현재까지가장많은연구가행해지고있다. 오늘날에는많은연구들에서실서증이 AD 환자의비교적초기단계에서발생하며 [9-11], AD군에서흔히관찰되는구두언어장애인이름대기장애 (anomia) 보다도더광범위하게나타난다고언급하고있다 [12-14]. 글자를쓰는행위는의미, 철자법등을포함하는언어능력뿐만아니라 Table 2. Subtypes and examples of spelling errors Subtypes Examples Phonological plausible error wade waid Phonological implausible error Substitution slush sluch Omission fruit frit Transposition yacht yatch Addition dusk ducsk Homophone confusion scene seen Lexicalization flig flag 운동적요소 (motor component), 주의력 (attention), 작업기억 (working memory), 시공간적능력 (visuospatial ability) 등의여러인지능력이투영된하나의산물이다 [14, 15]. 따라서이와연관된손상에의하여다양한양상으로오류가나타날수가있다. 물론 AD 군의경우는위와같이인지기능과관련있는많은영역에서의퇴보 (degradation) 로인하여실서증의양상이다소이질적으로나타날수가있다. 그러나실서증은 AD의인지기능손상과관련하여몇가지로구분되어질수있으므로, 실서증의하위유형을분류하는것은진단의기초를제공할뿐만아니라재활의측면에서도적절한중재 (intervention) 를제공할수있다. 따라서, 본장에서는 AD 환자군의실서증에관한비교적최근의연구동향을실험연구를고찰하는것과더불어, 철자및쓰기- 운동기제상에서의오류양상이어떠한기제에의해손상되는지살펴보고자한다. AD에관한대부분의연구는철자단계의장애, 즉중추실서증중어휘통로의손상에기인한어휘실서증에초점을맞추어오류양상을보고하고있다. 그이유는 AD군이갖는신경학적손상이의미기억손실과연관되어있기때문으로생각된다. 다시말해서, 의미 -어휘소의손상에기인한어휘통로의손상으로, 상대적으로보존되는음운통로에의하여철자처리를수행하게되며, 결론적으로음소와자소의대응이불일치한불규칙단어를수행하면서 PPE를보이게되는것이다. 따라서어휘실서증은 AD 환자의실서증에관한초기연구에해당하는 Rapcsak 등 [16] 과 Lambert 등 [17] 의연구에이르기까지 AD군의가장대표적인실서증양상으로보고된다. 경도-중도중증도를가진 AD군과정상군의수행을비교한선행연구 [11, 16] 에서는규칙, 불규칙, 비단어과제를시행한결과, 불규칙단어에서만환자군과정상군간에유의미한차이를보이는것을보고하면서, AD 는어휘철자체계의선택적손상을가지며상대적으로음운철자체계는보존됨을설명하였다. 그리고이러한오류는자소어휘소퇴행의증거라고주장하였다. 위와같은맥락에서 AD에관한대부분의선행연구들은 [11, 15, 16, 18-25], AD 환자가불규칙단어쓰기에서 PPE 오류를보이며이는어휘통로의손상에기인한다고주장하였다. 어휘실서증과더불어, AD 환자에있어서음운통로의손상에기인한음운실서증또한병의진행에따라발생할수있는유형이다. Platel 등 [26] 은 22 명의경도 -중도환자에게규칙, 불규칙, 비단어쓰기과제를시행하였으며이를 9-12개월간격으로종단추적하였다. 그결과, 환자들이불규칙단어에서 PPE와함께비단어에서도 PIE를보였으며, AD의철자오류를불규칙단어에서소수의 PPE를보이는초기단계, 비단어에서 PIE를보
6 윤지혜 나덕렬 김향희 이는중간단계, 단어종류에상관없이오류를보이는후기의 3 단계로나눌수있다. 비교적최근에는 23명의경도-중도 AD 환자군에서어휘실서증, 음운실서증및두가지형태를모두가진혼합실서증 (mixed agraphia) 이관찰되었다고보고하면서 [27, 28], AD의오류양상은상당히이질적이라는결론을내린연구도있다. 상기와같이, 음운실서증에관한논문을고찰하다보면비단어에서의 PIE가 AD 환자에서관찰되었다는연구 [16, 18, 21, 23-31] 가있지만, 치매의중증도와연관지어살펴보면음운실서증은병의초기단계에서는크게두드러지는주요오류유형은아닐것이라는의견이지배적임을알수있다. 의미실서증은주로음은같고글자는다른동음이자 (homophone) 를듣고받아쓰기를통하여확인되는실서증의한형태이다. Neils 등 [30] 과 Glosser 등 [32] 은 AD 군과정상군의비교를통하여환자군이동음이자에서의오류를보이는것과관련하여, 이러한오류가자소산출어휘소 (graphemic output lexicon) 으로연결되는의미체계단계의손상에기인한다고설명하였다 [30, 32, 33]. 중추단계에서말초단계로넘어가는단계에서발생할수있는장애의유형에는자소-버퍼장애가있다. 먼저, AD 환자의경우는서론에서이미언급하였듯이손상의범위가광범위하므로일반적인인지손상, 주의력장애등이동반될수있다. 이중, 특히철자및쓰기 -운동단계에직접적으로영향을주는것은자소- 버퍼장애로서, 이것이집행기능에속하는작업기억의손상과연관되어있다고보고된다 [5]. 이단계에손상이있으면쓰기-운동단계를통해글자가산출되는동안, 임시로저장되었던단어의자소표상이사라져자소치환, 생략, 대치등의오류가발생할수있다. 이러한관점에서 AD 환자들이단어의길이가증가할수록오류의빈도가증가하는것을보고한연구 [11, 19, 27] 도있다. 철자및쓰기 -운동단계의마지막에해당하는말초단계에서의장애를보고한연구로는다음과같다. 먼저, 이서장애에관한연구로는알파벳철자의대문자와소문자를전환하는 (crosscase transcription) ( 예. a A, D d) 과제수행시, 대문자와소문자쓰기간의수행의차이및오류가보고되었다 [4, 34, 35]. 이외에비교적초기연구에해당하는 Horner 등 [36] 은 20 명의경도-중도환자중 6명의환자가말초단계의오류를보인다고보고하면서, 이들이부적절한글자형성및글자의공간적배치오류등을보인다고하였으며, 이와유사한오류유형은많은연구 [24, 38, 39] 에서밝혀졌다. 유사한맥락에서중추철자오류와함께말초쓰기 -운동장애가 AD 환자에게서빈번히나타나는특징이라고보고한연구 [16, 37, 40] 도있으며, Platel 등 [26] 은이것이중추단계의손상이후에관찰된다는실서증이라 고하였다. 물론, AD의초기단계에쓰기-운동오류가관찰되었지만 [41], 일반적으로는 AD 진행단계에있어서말초실서증은비교적후기단계에관찰된다는견해가일반적이며 [37, 42], 상기보고와같이 AD 초기단계에서의말초실서증은소수의증례연구에서만보고되고있다. 중추실서증에비하여말초실서증에관한연구는그발생빈도나오류분석에있어서체계적이지못한실정이므로, 추후이와연관된후속연구가필요할것으로사료된다. Table 3은 AD 환자군을대상으로한실험연구의환자정보및쓰기수행결과를정리한것이다. 2. 전두측두엽치매 (FTLD) 병의초기에주로측두엽과두정엽이손상되는 AD에비해주로전두엽과측두엽손상부터시작되는전두측두엽치매 (FTLD) 는, 그임상양상에따라전두측두치매 (frontotemporal dementia, FTD), 의미치매 (semantic dementia, SD), 그리고진행성비유창실어증 (progressive nonfluent aphasia, PNFA) 으로분류된다 [49]. 측두엽전반부의병변으로시작되는 SD 환자는, AD 환자와유사하게철자단계의오류를보인다고하였으며, 특히예측불가한철자가포함된단어쓰기에서 PPE가관찰된다고하였다 [49-64]. 그러나 AD와는다르게쓰기-운동단계에서의오류는거의관찰되지않는것이일반적인데 [57, 64-67], 이러한이유는 SD 환자들이실행이나시공간 / 구성적인능력이보존되기때문이다. 현재까지 SD 환자의실서증에관한연구에는 3편의임상보고 [58, 61, 68] 와 1편의집단연구 [69] 가있다. 특히 Graham 등 [69] 은 SD군에서병의초기단계를제외하고는위에서언급된것과마찬가지로철자와음소가불일치하는단어에서 PPE를보인다고하였다. 또한비단어수행시에는크게어려움을보이지않았으며, SD 환자의철자오류는의미체계의손상에서기인하는것이라고설명하였다. PNFA는발병초기에좌반구의실비우스주위피질에비대칭적인위축을보이며, 다른인지기능의두드러진변화없이발병후수년동안구두언어장애만이주로관찰된다. 따라서대부분의연구가이에초점을맞추어행해졌으며문어장애에대한실험연구는거의없는실정이다. Croot [70] 은 1982년부터 1997년까지의 PNFA를대상으로한영어로쓰여진연구들을고찰하면서, 연구환자의약 80% 에해당하는환자가철자및쓰기장애를보였다고보고하였다. 이러한결과는많은 PNFA 환자의많은수가구어장애와함께문어장애를동반하고있고, 또한
치매와실서증 7 Table 3. Summary of demographic characteristics of subjects, stimuli, and error types in 23 studies on agraphia in Alzheimer s disease No. of AD Mean Mean of educa- MMSE* Ref. Spelling Motoric-writing no. Year Authors subjects age (SD) tion level score (SD)/ Stimuli errors errors (M:F) (yr) (SD) (yr) severity 43 1989 Glosser 12 (6:6) 65.83 (12.85) 13.00 (3.16) 16.55 (4.79)*/ 16 regular, 16 irregular Phonologically Nonlinguistic & Kaplan mild to words accurate regulation errors moderate error, phonologically inaccurate spelling errors 16 1989 Rapcsak 11 76.0 13.9 12.9* Regular, irregular, PPE, PIE et al. nonwords 26 1993 Platel 22-7 10-26* 10 regular, 10 irregular, PPE, Graphomotor et al. 10 nonwords PIE (Substitution, errors (reliance omission, insertion) on capital letter, separated & shaky letter) 30 1995 Neils 23 70.00 (7.17) 13.83 (3.00) 22.6 (2.45)*/ Copying 62 words; writing PPE, letter et al. mild to dictation 70 real words, errors (PIE) 20 regular, 20 irregular, 20 nonwords 20 1995 Penniello 11 56-74 8 10-26*/ 10 regular, 10 irregular, PPE, Allographic errors et al. mild to 10 nonwords non-phonological moderate spelling errors 19 1995 Neils 20 (11:9) 70.15 (7.36) 13.70 (3.21) 22.70 (2.72)* 25 pair of homophone PPE (homophone Construction et al. words, 20 nonwords, confusion), PIE dysgraphia copying 62 (41 words, (difficulty forming 21 nonwords) words letters, slow rate and laborious writing 22 1996 Lambert 12 (9:3) 61-82 6 11 to 25*/ 10 regular, 10 irregular, PPE, Graphemic et al. mild to 10 nonwords PIE (substitution, buffer, moderate transposition, allographic errors deletion, additions), graphomotor error (letter malformation) 11 1996 Croisile 33 (14:19) 68.9 (6.7) 12.2 (3.4) Mild 20.6 (2.2)*, Writing to dictation and Phonologically et al. moderate spelled orally (18 accurate errors, 12.6 (2.9)* regular, 18 ambiguous, phonologicalyl 18 irregular, 18 nonwords, inaccurate errors, 12 function words) substitutions 31 1996 Aarsland 16 (11:5) 72.4 10.4 (2.8) 21.1* 20 regular, 30, irregular, Lexical accuracy, et al. (4 mild, 36 nonwords nonlexical accuracy 12 moderate) 37 1997 Hughes 31 (4:27) Minimal Minimal Minimal 24-28*, 72 single syllable word Phonologically Allographic errors et al. (11 minimal, 77.4 (8.5) 9.8 (1.8) mild 16-23* (24 predictable, acceptable errors, 20 mild) mild mild 24 unpredictable, PIE 78.9 (7.9) 9.9 (1.9) 24 irregular), 26 letter copying, cross-case transcription 38 1998 Neils- 1 (male) 78 14 22*/ 36 words Letter omission, Poorly formed strunjas moderate addition, substitution, letter, stroke et al. transposition omission, superimposed letters. perseveration (Continued to the next page)
8 윤지혜 나덕렬 김향희 Table 3. (Continued from the previous page) No. of AD Mean Mean of educa- MMSE* Ref. Spelling Motoric-writing no. Year Authors subjects age (SD) tion level score (SD)/ Stimuli errors errors (M:F) (yr) (SD) (yr) severity 32 1999 Glosser 23 (15:8) 72.2 13.3 97.4 / 24 regular, Regularization, et al. mild to 24 ambiguous, orthographic related, moderately 24 irregular, unrelated errors, severe 54 nonwords lexicalization, phonemic related, neologism 44 1999 Slavin 16 (4:12) 78.5-12.88*/ Writing cursive letter perseveration et al. mild to l (four times) with of stroke severe varying levels of visual feedback 27 2000 Pestell 24 Mild: Mild Mild 12 regular, 12 irregular, PPE, PIE et al. 78.9 (6.2), 10.4 (2.1), 21.2 (3.0)*, 8 nonwords moderate: moderate moderate 75.8 (6.8) 10.3 (2.1) 14.2 (2.0)* 33 2002 Karvie & 14 (8:6) 68.93 (7.91) 13.64 (3.39) 22.14 (2.25)*/ 20 regular/irregular Neils-Str- mild words, 24 pairs of unjas homophone words 28 2003 Luzzatti 23 (11:12) 68.4 (6.6) 9.8 (5.2) 19.73 (3.48)*/ 80 regular, 55 irregular, PPE, PIE, semantic et al. mild to 25 non words and morphological moderate substitution 45 2003 Ardila 1 (female) 50 16 91 8 words, 10 nonwords, PPE, omission, et al. copying 44 words addition 46 2003 Cortese 61 77.5 (60-93) 14.3 Very mild 20 real word, 20 regular et al. (CDR 0.5), mild words, 20 irregular words AD (CDR 1) 47 2004 Groves- Mild 45 9 Mild AD (19 )*, 35 real and 5 nonwords Wright 14 (7:7) moderate et al. Moderate AD (13-18)* 14 (9:5) 15 2005 Carthery Mild Mild: 1.33 (4.53), Mild 40 nonwords and Regularization, Graphomotor et al. 15 (9:6), 73.93 (9.97), 11.92 (5.72) 21.73 (2.63)* 40 irregular words (substitution, errors moderate moderate: moderate omission, addition, (perseveration) 13 (7:6) 74.38 (7.90) 16.69 (2.39)* transposition) 48 2006 Werner 31 MCI: MCI: MCI :26.6 (2.4)* Copying words Slow rate, et al. MCI (18:13) 76.8 (6.5) 13.0 (2.7) AD: 23.7 (2.8)* and paragraph lower pressure 22 mild AD: AD: AD (11:11) 79.9 (6.5) 11.7 (2.5) 25 2007 Silveri 22 mild, Mild: 11.14 (4.73), Mild 46 words and PPE, PIE, Motor pattern et al. 14 severe 70.9 (8.57), 10.43 (4.72) 21.50 (3.19)*, 12 nonwords lexicalization (omission, severe: severe repetition 67.43 (9.47) 12.86 (2.73)* of stroke), allographic errors 17 2007 Lambert 59 (18:41) 73.15 (6.7) 9.1 (1.4) 21.8 (3.3)* 24 regular, 24 irregular, PPE, PIE Graphomotor, et al. 24 nonword allographic errors *Mini-Mental State Exam (Forstein & Forstein & McHugh, 1975) for classifying severity of dementia; Mattis Dementia Rating Sclae (MDRS) (Mattis, 1988) for classifying severity of dementia; Clinical Dementia Rating (CDR, Hughes et al., 1982) for classifying severity of dementia; Neuropsi-Brief Neuropsychological Test Battery for Spanish Speakers (Ostrosky, Ardila, & Rosselli, 1999) for classifying severity of dementia; PPE, phonologically plausible errors; PIE, phonologically implausible errors. PNFA가전보문형식의문장산출이나형태론적인오류를보였으며, 이러한문어장애는이들이가진구어장애가그대로투영된하나의산물이라고결론지었다. PNFA의오류유형에관해 서는자세하게보고된것은없지만, PPE 및자소생략, 자소치환의오류가간단하게보고된연구 [55, 71] 는있다. 두연구 [55, 71] 에서는모두환자가쓰기-운동적측면에서, 글자의형성이나
치매와실서증 9 외양에서는문제를보이지않지만, 쓰기수행시다소지연된반응시간이관찰되었다고보고하였다. 전두엽과측두엽의전방부위축이특징적으로관찰되는 FTD 환자군에서는, 철자오류가보고 [55] 된것을제외하고는실서증에초점을맞춘연구가거의없는실정이다. 그러나 Menichelli 등 [72] 의 FTD 증례연구에서는환자가 PPE, PIE와더불어소문자에비하여대문자쓰기에서어려움을보이는이서실서증양상을두드러지게보였다고보고하면서소문자와대문자는형태에관한정보는신경학적으로각각독립적으로저장되어있다고주장하였다. 3. 후방피질위축 (PCA) PCA는 AD, 피질하교증 (subcortical glosis), 크로즈펠트야콥병 (Creutzfeldt-Jakob disease) 등의여러병리학적원인에의하여, 후두-측두엽및후두 -두정엽부위에위축이발생하는것이특징이다. 따라서병의초기에다른인지기능은비교적유지되는반면, 시각실인증, 실독증및안구운동실행증 (oculomotor apraxia), 시각실조증 (optic ataxia), 동시실인증 (simultanagnosia) 이포함된발린트증후군 (Balint s syndrome) 의증상이병의초기부터두드러지게된다 [73, 74]. 실서증은 PCA가보일수있는주요증상중의하나이지만 [73], 대부분의연구 [73-77] 는그임상증상만을간단히보고하였으며, 적절한정보를제공하는연구는소수에불과하였다 [78-83]. 이들의실서증양상은알아볼수없는글자형태, 용지에서의글자의위치, 글자와글자사이의공간문제, 줄의방향, 획의생략및첨가등의말초단계의문제등이두드러지는것이특징이다 [79-82]. 위의연구자들은이러한쓰기 -운동장애를 공간실서증 (spatial agraphia) 혹은 구심실서증 (afferent dysgrpahia) 이라고지칭하면서, 이러한오류양상이 PCA의심각한시각적 (visual) 손상에기인한것으로설명하였다. 물론몇몇연구들은 PCA 환자에서철자장애를보고하기도하였으나 [73, 76, 78, 80, 81, 83], 쓰기-운동단계의오류와비교해서는관찰의정도가미비한실정이다. 4. 루이체치매 (DLB) 파킨슨증상 (Parkinsonism) 에선행해서치매의증상이나타나거나파킨슨증상이나타난초기에치매증상을동반하는것으로알려진 DLB의신경심리학소견에관한연구는비교적최근에시작된것으로, 현재까지 Hansen 등 [84] 과 Connor 등 [85] 의연구가있다. 두연구모두 DLB 환자군과 AD 환자군을비교 하면서, DLB 환자들이같은중증도의 AD 환자들에비하여받아쓰기과제에서의수행력이더낮음을보고하였다. 그러나자극의종류나오류양상에대해전혀기술되어있지않으므로 DLB 환자군이보인실서증이어떠한특징을가지고있는지는알수없다. 다만, 논의에서 DLB 환자가심도의시공간적장애를보였다고언급하였으므로 [84], 쓰기과제수행시, 상기장애로인한쓰기-운동단계의오류유형을보였을것이라고유추해볼수있다. 5. 혈관치매 (VD) 뇌혈관질환에의한뇌손상으로초래되는 VD의실서증에관한연구의경우, VD와 AD 에게웨스턴실어증검사를시행하고수행력을비교한연구 [86, 87] 가전부이다. Powell 등 [86] 의경우는두집단모두치매의중증도가같은경우유사한수행력을보였다고보고하였으나, Kertesz와 Clydesdale [87] 의경우는동일한치매중증도의경우 VD가 AD 보다더낮은수행력을보이며, 특히쓰기하위검사는두환자군을구분하는데유용한하위검사라고기술하였다. 또한낱글자 (letter) 받아쓰기와문장베껴쓰기에서 VD가더욱어려움을보이며 [87], 이를이서실서증혹은자소운동양식 (grapho motor pattern) 단계에서의오류일것이라고주장하였다. 이외에 VD 가철자오류와줄맞추어쓰기에서어려움을가지며, 중추및말초실서증모두를보일수있다고보고하였다 [88]. Lesser [89] 는 VD 에있어서구두철자 (oral spelling) 에서는오류가없으나문어철자수행시수행력차이를보고하면서이것이철자쓰기처리단계중말초단계의장애와연관이있다고설명하였다. 정리하자면, 현재까지 VD 환자군에서철자와쓰기-운동오류모두가보고되었으므로, 추후체계적인실험연구를통하여상기오류의기제를탐색하는작업이필요할것으로사료된다. 6. 피질기저핵변성 (CBD) 대뇌피질, 기저핵, 그리고흑질의신경세포변성으로인하여비대칭적인파킨슨증상과실행증 (apraxia), 근간대증 (myoclonus), 핵상주시마비 (supranuclear gaze palsy) 등의임상특징을보이는 CBD 환자의경우말초실서증의하위유형인실행실서증을보인다는임상연구가흔히보고되어지고있다 [90-93]. Moreaud 등 [94] 과 Heilman 등 [95] 은증례보고를통하여이러한쓰기장애가 CBD의임상양상중의하나인실행증 (dyspraxia) 에서기인한다고설명하였다. 그러나실행실서증이외의오류도보고되었는데, Graham 등 [93] 의경우, 실행증이있음에도
10 윤지혜 나덕렬 김향희 불구하고글자를쓰는것에는크게어려움이없으나, 대문자- 소문자전환시오류를보이는환자를보고하면서이것이이서단계의장애라고설명하였다. 이와함께질환의초기단계에서는어휘실서증양상이두드러지다가병이진행되면서음운적으로부적절한오류 (PIE) 를보이는환자를보고하면서이러한진행양상이 AD 실서증의진행양상과유사하거나 [93], 분류할수없는 (unspecified) 철자오류를보이는 [96] 등 CBD에서의중추실서증도보고되었다. Fukui와 Lee [97] 의연구에서는 3명의 CBD 환자가실행실서증, 공간실서증, 이서단계의오류및철자단계의오류등을보였으며이렇게다양한양상은 CBD 환자의두정-후두-측두엽및기저핵과피질하-전두회로 (subcortical-frontal circuit) 로연결되는부위의퇴행과정과연관이있다고설명하였다. 7. 헌팅턴병 (HD) Table 4. Classification of error types on each dementia type Dementia type Spelling errors Motoric-writing errors AD SD PNFA FTD PCA DLB VD CBD HD PSP X, Errors reported in previous studies those ascribed to impairment of the designated writing system;, Errors reported, but mot specified in terms of their cause; X, Not reported. AD, Alzheimer s disease; SD, semantic dementia; PNFA, progressive nonfluent aphasia; FTD, frontotemporal dementia; PCA, posterior cortical atrophy; DLB, dementia with Lewy bodies; VD, vascular dementia; CBD, corticobasal degeneration; HD, Huntington s disease; PSP, progressive supranuclear palsy. X X 전두엽과두정엽의위축으로무도성운동및운동마비, 치매등의임상적특징을보이는 HD 의경우환자들의운동증상과관련이있는실서증연구가두드러진다. 12명의 HD 환자를대상으로알파벳소문자 l 을 4회쓰도록한후속도및정확도등을측정한결과수행시무도증 (chorea) 으로인한대자증 (macrographia) 양상이관찰되었다 [98]. 이와유사한맥락에서, Podoll 등 [99] 은 45 명의 HD 환자들이쓰기수행시무도적운동양상 (choreiform movement) 으로인하여글자위치의부정확성, 단어내의글자기울기의비일관성등을보였다고보고하였다. 또한, 병의중증도가중기, 후기에해당되는 HD 환자의경우자소의생략, 첨가, 대치, 보속등의철자오류가관찰되었으며, 이것이자소버퍼및구성단계의장애에기인한철자오류라고결론을지었다 [99]. 8. 진행핵상마비 (PSP) 피질하신경핵의병리적변화로인한 PSP의경우, 상핵성안근마비, 운동불능, 중심성강직, 목덜미근긴장이상, 가성연수마비, 치매등의임상적특징을보인다. 따라서환자의실서증양상은철자오류보다는쓰기-운동수행자체에초점이맞추어졌다. 특히쓰기과제수행시떨림 (cramp) 등으로인하여글자체를알아보기힘들며 [100], 소자증 (micrographia) 양상등이보고되었다 [101]. Podoll 등 [102] 은 6명의 PSP 환자의단어및문장받아쓰기를통해, 수행시관찰된알아보기힘든글자오류가미세한손가락움직임장애에기인한다고결론을내렸다. 또한, 이들은단어내의낱철자혹은문장내의단어를생략하는철자오류도보였는데, 이는종단주시마비 (vertical gaze palsy) 로인한시각적모니터링의손상에기인한결과일것이라고설명하였다. Table 4는선행연구에서보고된치매하위유형에따른철자및쓰기 -운동오류를분류한것이다. 결론치매환자군의실서증은특정병소를보이는뇌졸중환자에서관찰되는오류양상과유사하나, 그분배의측면에서는서로다르다. 즉, 뇌졸중환자와같이단순히하나의오반응유형을보일뿐만아니라, 각환자내에서도여러가지실서증양상이관찰되므로이를해석하는데어려움이있다. 이러한이유는서론에서이미언급하였듯이치매라는질환이뇌의어느한부분에서의손상이아닌, 그범위가보다광범위하므로철자및쓰기 -운동모델처리과정상에서더다양하고많은영역이침범을받을수가있기때문인것으로사료된다. 따라서, 치매군은관찰및실험연구에있어서다소이질적이며통제의어려움이따르는질환군에해당된다. 그러나치매는시간의진행에따라능력이점차퇴행하는특징을가지므로종단연구를통하여병의진행에따른철자및쓰기장애를추적관찰함으로써, 중증도에따른변화양상을확인하는것으로개개인이가진치매질환의이질성을어느정도극복할수있다. 본고에서는지금까지의치매의철자및쓰기장애에관한선
치매와실서증 11 행연구의대상군이경도-중등도단계의 AD 환자군에국한되어져있으며, 대부분이중추실서증의하위유형을분류하는것에많은시간을할애한것을확인할수있었다. 따라서추후연구에서는 AD 이외의다양한치매환자군을대상으로한실험연구의필요성이대두된다. 이를통하여실서증의중추적측면과말초적요소를재조명하고, 오류분석에있어서자세한준거를정립할수있다면, 여러가지특성이혼재하는치매하위유형간의감별진단에 쓰기 라는새로운측정방법을추가할수있는근거의견고한초석이될수있을것으로생각된다. 참고문헌 1. Leischner A. The agraphias. In: Vinken PJ, Bruyn GW. Handbook of clinical neurology. Vol. 4. Amsterdam: North-Holland Publishing Co. 1969; 141-80. 2. Ogle JW. Aphasia and agraphia. Report of the Medical Research Council of St. George s Hospital. London, 1867; 2: 28-122. 3. McCarthy RA, Warrington EK. Cognitive neuropsychology: a clinical introduction. San Diego (CA): Academic Press, 1990. 4. Ellis AW. Spelling and writing (and reading and speaking). In: Ellis AW. Normality and pathology in cognitive functions. London: Academic Press. 1982; 113-46. 5. Roeltgen DP, Heilman KM. Review of agraphia and proposal for an anatomically based neuropsychological model of writing. Appl Psycholinguist 1985; 6: 205-20. 6. Roeltgen DP. In: Heilman KM, Valenstein E. Clinical neuropsychology. 4th ed. New York: University Press. 2003; 126-45. 7. Rapcsak SZ, Beeson PM. Agraphia. In: Nadeau, SE, Gonzalez Rothi LJ, Crosson B. Aphasia and language: theory to practice. New York: The Guilford Press. 2000; 184-220. 8. Alzheimer A. Uber Eine eigenartige Erkrankung der Hirnrinde [About an intriguing disease of the cerebral cortex]. In Rottenberg D, Hochberg F. Neurological classics in modern translation. New York: Hafner Press. 1977; 41-3 (Original work published 1907). 9. Cummings J, Benson D, Hill M, Read S. Aphasia in dementia of the Alzheimer type. Neurology 1985; 35: 394-7. 10. Faber-Langendoen K, Morris JC, Knesevich JW, LaBarge E, Miller JP, Berg L. Aphasia in senile dementia of the Alzheimer type. Ann Neurol 1988; 23: 365-70. 11. Croisile B, Brabant MJ, Carmoi T, Lepage Y, Aimard G, Trillet M. Comparison between oral and written spelling in Alzheimer s disease. Brain Lang 1996; 54: 361-87. 12. Appell J, Kertesz A, Fisman M. A study of language functioning in Alzheimer s patients. Brain Lang 1982; 17: 73-91. 13. Murdoch BE, Chenery HJ, Wilks V, Boyle RS. Language disorders in dementia of the Alzheimer type. Brain Lang 1987; 31: 122-37. 14. Croisile B. Agraphia in Alzheimer s disease. Dement Geriatr Cogn Disord 1999; 10: 226-30. 15. Carthery MT, Mattos Pimenta Parente MA, Nitrini R, Bahia VS, Caramelli P. Spelling tasks and Alzheimer s disease staging. Eur J Neurol 2005; 12: 907-11. 16. Rapcsak SZ, Arthur SA, Bliklen DA, Rubens AB. Lexical agraphia in Alzheimer s disease. Arch Neurol 1989; 46: 65-8. 17. Lambert J, Giffard B, Nore F, de la Sayette V, Pasquier F, Eustache F. Central and peripheral agraphia in Alzheimer s disease: from the case of Auguste D. to a cognitive neuropsychology approach. Cortex 2007; 43: 935-51. 18. Croisile B, Carmoi T, Adeleine P, Trillet M. Spelling in Alzheimer s disease. Behavioural Neurology 1995; 8: 135-43. 19. Neils J, Roeltgen DP, Greer A. Spelling and attention in early Alzheimer s disease: evidence for impairment of the graphemic buffer. Brain Lang 1995; 49: 241-62. 20. Penniello MJ, Lambert J, Eustache F, Petit-Taboue MC, Barre L, Viader F, et al. A PET study of the functional neuroanatomy of writing impairment in Alzheimer s disease. The role of the left supramarginal and left angular gyri. Brain 1995; 118: 697-706. 21. Hillis A, Benzing L, Caramazza A. Dissolution of spelling in a patient with Alzheimer s disease: evidence for phoneme-to-grapheme correspondence rules. Brain Lang 1996; 55: 62-5. 22. Lambert J, Eustache F, Viader F, Dary M, Rioux P, Lechevalier B. Agraphia in Alzheimer s disease: an independent lexical impairment. Brain Lang 1996; 53: 222-33. 23. Graham NL. Dysgraphia in dementia. Neurocase 2000; 6: 365-76. 24. Forbes KE, Shanks MF, Venneri A. The evolution of dysgraphia in Alzheimer s disease. Brain Res Bull 2004; 63: 19-24. 25. Silveri MC, Corda F, Di Nardo M. Central and peripheral aspects of writing disorders in Alzheimer s disease. J Clin Exp Neuropsychol 2007; 29: 179-86. 26. Platel H, Lambert J, Eustache F, Cadet B, Dary M, Viader F, et al. Characteristics and evolution of writing impairment in Alzheimer s disease. Neuropsychologia 1993; 31: 1147-58.
12 윤지혜 나덕렬 김향희 27. Pestell S, Shanks MF, Warrington J, Venneri A. Quality of spelling breakdown in Alzheimer s disease is independent of disease progression. J Clin Exp Neuropsychol 2000; 22: 599-612. 28. Luzzatti C, Laiacona M, Agazzi D. Multiple patterns of writing disorders in dementia of the Alzheimer type and their evolution. Neuropsychologia 2003; 41: 759-72. 29. Neils J, Roeltgen D. Does lexical dysgraphia occur in early Alzheimer s disease? J Med Speech Lang Pathol 1994; 2: 281-9. 30. Neils J, Roeltgen DP, Constantinidou F. Decline in homophone spelling associated with loss of semantic influence on spelling in Alzheimer s disease. Brain Lang 1995; 49: 27-49. 31. Aarsland D, Hoien T, Larsen JP, Oftedal M. Lexical and nonlexical spelling deficits in dementia of the Alzheimer type. Brain Lang 1996; 52: 551-63. 32. Glosser G, Kohn SE, Sands L, Grugan PK, Friedman RB. Impaired spelling in Alzheimer s disease: a linguistic deficit? Neuropsychologia 1999; 37: 807-15. 33. Kavrie S, Neils-Strunjas J. Dysgraphia in Alzheimer s disease with mild cognitive impairment. J Med Speech Lang Pathol 2002; 10: 73-85. 34. Margolin D. The neuropsychology of writing and spelling: semantic, phonological, motor, and perceptual processes. Q J Exp Psychol A 1984; 36: 459-89. 35. Margolin D, Goodman-Schulman R. Oral and written spelling impairments. In: Margolin D. Cognitive neruopsychology in clinical practice. New York: Oxford University Press. 1992; 263-97. 36. Horner J, Heyman A, Dawson D, Rogers H. The relationship of agraphia to the severity of dementia in Alzheimer s disease. Arch Neurol 1988; 45: 760-3. 37. Hughes JC, Graham N, Patterson K, Hodges JR. Dysgraphia in mild dementia of Alzheimer s type. Neuropsychologia 1997; 35: 533-45. 38. Neils-Strunjas J, Shuren J, Roeltgen D, Brown C. Perseverative writing errors in a patient with Alzheimer s disease. Brain Lang 1998; 63: 303-20. 39. Venneri A, Pestell S, Caffarra P. Independent representations for cursive and print style: Evidence from dysgraphia in Alzheimer s disease. Cogn Neuropsychol 2002; 19: 387-400. 40. Graham N, Patterson K, Hodges J. Progressive dysgraphia: co-occurrence of central and peripheral impairments. Cogn Neuropsychol 1997; 14: 975-1005. 41. Piras MR, Cherchi R, Satta W, Masuri MR, Sini S, Pes M, et al. Alzheimer disease in Sardinian population: a neuropsychological and genetic study. Arch Gerontol Geriatr 1998; 6: 407-16. 42. Neils-Strunjas J, Groves-Wright K, Mashima P, Harnish S. Dysgraphia in Alzheimer s disease: a review clinical and research purposes. J Speech Lang Hear Res 2006; 49: 1313-30. 43. Glosser G, Kaplan E. Linguistic and nonlinguistic impairments in writing: a comparison of patients with focal and multifocal CNS disorders. Brain Lang 1989; 37: 357-80. 44. Slavin MJ, Phillips JG, Bradshaw JL, Hall KA, Presnell I. Consistency of handwriting movements in dementia of the Alzheimer s type: a comparison with Huntington s and Parkinson s diseases. J Int Neuropsychol Soc 1999; 5: 20-5. 45. Ardila A, Matute E, Inozemtseva I. Progressive agraphia, acalculia, and anomia: a single case report. Appl Neuropsychol 2003; 10: 205-14. 46. Cortese M, Balota D, Sergent-Marshall S, Buckner R. Spelling via semantics and phonology: exploring the effects of age, Alzheimer s disease, and primary semantic impairment. Neuropsychologia 2003; 41: 952-67. 47. Groves-Wright K, Neils-Strunjas J, Burnett R, O Neill MJ. A comparison of verbal and written language in Alzheimer s disease. J Commun Disord 2004; 37: 109-30. 48. Werner P, Rosenblum S, Bar-On G, Heinik J, Korczyn A. Handwriting process variables discriminating mild Alzheimer s disease and mild cognitive impairment. J Gerontol 2006; 4: 228-36. 49. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546-54. 50. Baxter DM, Warrington EK. Transcoding sound to spelling: single or multiple sound unit correspondence? Cortex 1987; 23: 11-28. 51. Snowden JS, Goulding PJ, Neary D. Semantic dementia: a form of circumscribed cerebral atrophy. Behav Neurol 1989; 2: 167-82. 52. Snowden JS, Neary D, Mann DMA, Goulding PJ, Testa HJ. Progressive language disorder due to lobar atrophy. Ann Neurol 1992; 31: 174-83. 53. Snowden JS, Griffiths HL, Neary D. Semantic dementia: autobiographical contribution to preservation of meaning. Cogn Neuropsychol 1994; 11: 265-88. 54. Snowden JS, Griffiths HL, Neary D. Semantic-episodic memory interactions in semantic dementia: implications for retrograde memory function. Cogn Neuropsychol 1996; 13: 1101-37. 55. Snowden JS, Neary D, Mann DMA. Fronto-temporal lobar degeneration: fronto-temporal dementia, progressive aphasia, semantic dementia. London: Churchill Livingstone, 1996. 56. Diesfeldt HF. Impaired and preserved semantic memory functions in dementia. In: Backman L. Memory functioning in dementia. Amsterdam:
치매와실서증 13 Elsevier Science. 1992: 227-63. 57. Diesfeldt HF. Progressive decline of semantic memory with preservation of number processing and calculation. Behav Neurol 1993; 6: 239-42. 58. Patterson K, Hodges JR. Deterioration of word meaning: implications for reading. Neuropsychologia 1992; 30: 1025-40. 59. Parkin AJ. Progressive aphasia without dementia: a clinical and cognitive neuropsychological analysis. Brain Lang 1993; 44: 201-20. 60. Hodges JR, Graham N, Patterson K. Charting the progression in semantic dementia: Implications for the organization of semantic memory. Memory 1995; 3: 463-95. 61. Hodges JR, Garrard P, Patterson K. Semantic dementia. In: Kertesz A, Munoz DG. Pick s disease and Pick complex. New York: Wiley-Liss. 1998; 83-104. 62. De Bleser R, Weis J, Schwarz M. Primary progressive aphasia: a 14-year follow-up study. Brain Lang 1996; 55: 76-8. 63. Kertesz A, Davidson W, McCabe P. Primary progressive semantic aphasia: a case study. J Int Neuropsychol Soc 1998; 4: 388-98. 64. Schwarz M, De Bleser R, Poeck K, Weis J. A case of primary progressive aphasia: a 14-year follow-up study with neuropathological findings. Brain 1998; 121: 115-26. 65. Warrington EK. Selective impairment of semantic memory. Q J Exp Psychol 1975; 27: 635-57. 66. Schwartz MF, Chawluk JB. Deterioration of language in progressive aphasia: a case study. In: Schwartz MF. Modular deficits in Alzheimertype dementia. London: MIT Press. 1990: 245-96. 67. Scholten IM, Kneebone AC, Denson LA, Fields CD, Blumbergs P. Primary progressive aphasia: serial linguistic, neuropsychological and radiological findings with neuropathological results. Aphasiology 1995; 9: 495-516. 68. Sasanuma S, Patterson K. Non-semantic reading in Kanji and English: universal and language-specific features. In: de Gelder B, Morais J. Speech and reading: a comparative approach. Hove, East Sussex: Erlbaum Taylor & Francis. 1995: 207-25. 69. Graham NL, Patterson K, Hodges JR. The impact of semantic memory impairment on spelling: evidence from semantic dementia. Neuropsychologia 2000; 38: 143-63. 70. Croot KP. Phonological disruption in progressive aphasia and Alzheimer s disease. PhD Thesis, University of Cambridge, 1997. 71. Kartsounis LD, Crellin RF, Crewes H, Toone BK. Primary progressive non-fluent aphasia: a case study. Cortex 1991; 27: 121-9. 72. Menichelli A, Rapp B, Semenza C. Allographic agraphia: a case study. Cortex 2008; 44: 861-8. 73. Benson DF, Davis RJ, Snyder BD. Posterior cortical atrophy. Arch Neurol 1988; 45: 789-93. 74. Berthier ML, Leiguarda R, Starkstein SE, Sevlever G, Taratuto AL. Alzheimer s disease in a patient with posterior cortical atrophy. J Neurol Neurosurg Psychiatry 1991; 54: 1110-1. 75. Kiyosawa M, Bosley TM, Chawluk J, Jamieson D, Schatz NJ, Savino PJ, et al. Alzheimer s disease with prominent visual symptoms: clinical and metabolic evaluation. Ophthalmology 1989; 96: 1077-86. 76. Graff-Radford NR, Bolling JP, Earnest F, Shuster EA, Caselli RJ, Brazis PW. Simultanagnosia as the initial sign of degenerative dementia. Mayo Clinic Proceedings 1993; 68: 955-64. 77. Victoroff J, Ross GW, Benson F, Verity MA, Vinters HV. Posterior cortical atrophy: neuropathologic correlations. Arch Neurol 1994; 51: 269-74. 78. Freedman L, Selchen DH, Black SE, Kaplan R, Garnett ES, Nahmias C. Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. J Neurol Neurosurg Psychiatry 1991; 54: 443-8. 79. Levine DN, Lee JM, Fisher CM. The visual variant of Alzheimer s disease: a clinicopathologic case study. Neurology 1993; 43: 305-13. 80. Ross SJM, Graham N, Stuart-Green L, Prins M, Xuereb J, Patterson K, et al. Progressive biparietal atrophy: an atypical presentation of Alzheimer s disease. J Neurol Neurosurg Psychiatry 1996; 61: 388-95. 81. Ardila A, Rosselli M, Arvizu L, Kuljis RO. Alexia and agraphia in posterior cortical atrophy. Neuropsychiatry Neuropsychol Behav Neurol 1997; 10: 52-9. 82. Rogelet P, Delafosse A, Destee A. Posterior cortical atrophy: an unusual feature of Alzheimer s disease. Neurocase 1996; 2: 495-501. 83. O Dowd BS, de Zubicaray GI. Progressive dysgraphia in a case of posterior cortical atrophy. Neurocase 2003; 9: 251-60. 84. Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, et al. The Lewy body variant of Alzheimer s disease: a clinical and pathologic entity. Neurology 1990; 40: 1-8. 85. Connor DJ, Salmon DP, Sandy TJ, Galasko D, Hansen LA, Thal LJ. Cognitive profiles of autopsy-confirmed Lewy body variant vs. pure Alzheimer s disease. Arch Neurol 1998; 55: 994-1000. 86. Powell AL, Cummings JL, Hill MA, Benson DF. Speech and language alterations in multi-infarct dementia. Neurology 1988; 38: 717-9. 87. Kertesz A, Clydesdale S. Neuropsychological deficits in vascular dementia vs. Alzheimer s disease. Arch Neurol 1994; 51: 1226-31. 88. Carey ME, Giovannetti T, Libon DJ. A comparison of written discourse
14 윤지혜 나덕렬 김향희 in Alzheimer s disease and subcortical ischemic vascular dementia. Arch Clin Neuropsychol 1999; 14: 45-6. 89. Lesser R. Superior oral to written spelling: evidence for separate buffers? Cogn Neuropsychol 1990; 7: 347-66. 90. Riley DE, Lang AE, Lewis MB, Resch L, Ashby P, Hornykiewicz O, et al. Cortical-basal ganglionic degeneration. Neurology 1990; 40: 1203-12. 91. Mimura M, White RF, Albert ML. Corticobasal degeneration: neuropsychological and clinical correlates. J Neuropsychiatry Clin Neurosci 1997; 9: 94-8. 92. Blasi V, Labruna L, Soricelli A, Carlomagno S. Limb-kinetic apraxia: a neuropsychological description. Neurocase 1999; 5: 201-11. 93. Graham NL, Zeman A, Young AW, Patterson K, Hodges JR. Dyspraxia in a patient with corticobasal degeneration: the role of visual and tactile inputs to action. J Neurol Neurosurg Psychiatry 1999; 67: 334-44. 94. Moreaud O, Naegele B, Pellat J. The nature of apraxia in corticobasal degeneration: a case of melokinetic apraxia. Neuropsychiatry Neuropsychol Behav Neurol 1996; 9: 288-92. 95. Heiman KM, Coenen A, Kluger B. Progressive asymmetric apraxic agraphia. Cog Behav Neurol 2008; 21: 14-7. 96. Beatty WW, Scott JG, Wilson DA, Prince JR, Williamson DJ. Memory deficits in a demented patient with probable corticobasal degeneration. J Geriatr Psychiatry Neurol 1995; 8: 132-6. 97. Fukui T, Lee E. Progressive agraphia can be a harbinger of degenerative dementia. Brain Lang 2008; 104: 201-10. 98. Pillips JG, Bradshaw JL, Chiu E, Bradshaw JA. Characteristics of handwriting of patients with Huntington s disease. Mov Disord 1994; 9: 521-30. 99. Podoll K, Caspary P, Lange HW, Noth J. Language functions in Huntington s disease. Brain 1988; 111: 1475-503. 100. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy. Arch Neurol 1964; 10: 333-59. 101. Dix MR, Harrison MJG, Lewis PD. Progressive supranuclear palsy (the Steele-Richardson-Olszewski syndrome): a report of 9 cases with particular reference to the mechanism of the oculomotor disorder. J Neurol Sci 1971; 13: 237-56. 102. Podoll K, Schwarz M, Noth J. Language functions in progressive supranuclear palsy. Brain 1991; 114: 1457-72.