Brain & NeuroRehabilitation Vol. 6, No. 1, March, 2013 http://dx.doi.org/10.12786/bn.2013.6.1.26 뇌졸중환자에서장기적인기능변화와관련된요인분석 고려대학교의과대학재활의학교실, 1 삼육서울병원재활의학과 임지훈ㆍ한아름ㆍ류병주 1 ㆍ편성범 Long-term Functional Outcome and Related Factors in Stroke Patients Ji Hoon Lim, M.D., Ah Reum Han, M.D., Byong Ju Ryu, M.D. 1 and Sung Bom Pyun, M.D. Department of Rehabilitation Medicine, Korea University College of Medicine, 1 Department of Rehabilitation Medicine, Sahmyook Medical Center Objective: To investigate long-term functional changes and its underlying factors in stroke patients. Method: Data were collected retrospectively from the stroke patients who had been completed at least 2 times of functional evaluation after discharge. 60 stroke patients were included and we investigated long-term change of motor, cognition and activities of daily living score at 6 months from the onset and the last score during the follow up period. The motor function included manual function test (MFT), Korean version of Berg balance scale (K-BBS), cognitive function by Korean version of mini-mental status examination (K-MMSE), activities of daily living by Korean version of modified Barthel index (K-MBI). To identify the factors influencing long-term function outcome after stroke, biographical data and risk factors were collected and bivariate correlation analysis was performed. Results: The mean duration of follow-up was 23.4 months and MFT, BBS, MMSE, and K-MBI scores showed no significant difference between 6 months from the onset and final evaluation. History of recurrent stroke (p = 0.007) and hypertension (p = 0.017) were significantly related with decline of cognition during follow up period. All the other independent variables were not statistically significant. Conclusion: None of the function showed significant changes during the 2 year of mean follow-up period. Recurrent stroke and hypertension were significant predictor for decline of cognitive function. Our results suggest that secondary prevention including blood pressure control is important to prevent decline of cognitive function after stroke. (Brain & NeuroRehabilitation 2013; 6: 26-32) Key Words: activities of daily living, cognition, postural balance, stroke, upper extremity 서론 뇌졸중은운동및인지기능, 일상생활동작수행능력에심각한저하를초래하는주된질환으로뇌졸중발생후기능회복에대해많은연구가이루어졌다. 이전의연구에따르면뇌졸중환자의 55 75% 에서상지의편마비가발생하며 1 회복의대부분이뇌졸중발생후 6개월이내에일어나는것으로보고하였다. 2 그리고뇌졸중후 95% 에서 12.5주이내최대일상생활동작수행능력에도달하였고 80% 에서는발병후 6주이내에최대일상생활동작수행능력에들어선다고발표하였다. 1 뇌졸중에의한보행기능 접수일 : 2012 년 9 월 21 일, 1 차심사일 : 2012 년 12 월 5 일, 2 차심사일 : 2013 년 1 월 16 일, 3 차심사일 : 2013 년 1 월 22 일, 4 차심사일 : 2013 년 2 월 12 일, 게재승인일 : 2013 년 2 월 12 일교신저자 : 편성범, 서울시성북구인촌로 73( 안암동 5 가 ) 136-705, 고려대학교의과대학재활의학교실 Tel: 02-920-6483, Fax: 02-929-9951 E-mail: rmpyun@korea.ac.kr 의장애도흔하게발생하며, 3 생활의독립성, 삶의질, 사회적참여등에영향을미치는데보행기능은뇌졸중발생후 3 6개월까지향상을이루다가그이후로는정체기에접어든다고보고하였다. 4-7 그외에도뇌졸중발생후기능의변화를알아보려는시도는많이이루어져왔으나대부분이발생후 1년미만의경과관찰기간동안기능의회복정도를확인하기위한연구였으며 1년이상의만성기에서장기간기능의변화를알아보기위한연구는부족한실정이다. 본연구는뇌졸중환자를대상으로장기적인운동기능, 인지기능과일상생활동작수행능력의변화양상을알아보고만성기에서기능의변화, 특히 6개월이지난시점에서기능의감소에영향을미치는요인을알아보고자연구를진행하였다. 26
임지훈외 3 인 : 뇌졸중환자에서장기적인기능변화와관련된요인분석 연구대상및방법 1) 연구대상본연구는 2005년 12월부터 2010년 10월까지고려대학교안암병원재활의학과에서뇌졸중으로입원을하였거나외래를통해진료를받았던환자를대상으로후향적으로의무기록을통해정보를수집하였다. 본연구의대상은발병후 1년이상경과관찰이가능하였던환자로외래경과관찰기간동안 6개월시점과발병후 1년이상의시점에적어도 2번이상상지기능평가 (manual function test), 8 한국판버그균형검사 (Korean version of Berg balance scale), 9 한국판간이정신상태검사 (Korean version of mini-mental status examination, K-MMSE), 10 한국판수정바델지수 (Korean version of modified Barthel index, K- MBI) 11 검사를시행하였던환자를대상으로하였다. 장기적인운동기능, 인지기능, 일상생활동작수행능력에영향을미칠수있는진행성질환이있는환자는제외하였으며뇌졸중의기왕력을가진환자와조사기간중뇌졸중의재발이일어난환자는연구대상에포함하였다. 총 60명의환자가포함되었고그중남자는 33명, 여자는 27명이었으며, 발병당시의평균나이는 62.4세였다. 2) 연구방법의무기록을통해각환자의성별, 나이, 뇌병변의주반구, 뇌졸중의형태 ( 뇌경색또는뇌출혈 ) 및한국판미국국립보건원뇌졸중척도 (K-NIHSS) 등의기본정보와뇌졸중후기능변화에영향을끼칠수있는인자로뇌졸중의기왕력, 외래추적기간동안뇌졸중의재발, 고혈압, 심혈관질환 ( 부정맥, 심근경색 ) 의유무, 당뇨, 경직, 낙상, 우울증, 재활치료유지유무등을조사하였다. 조사기간동안에상하지경직으로인해항경직제를복용하거나개정된 Ashworth 척도 (Modified Ashworth Scale, MAS) 를통해근긴장도의증가가확인이된경우, 입원중이거나퇴원후경과관찰기간동안항우울제처방을하였던경우, 마지막으로경과관찰시 1주 1회이상의료기관을통하여재활치료를유지하고있는경우일때해당군으로포함하였다. 뇌졸중후장기경과관찰을통해운동과인지기능및일상생활동작수행능력의변화를알아보기위해각환자를대상으로뇌졸중발병후 6개월시점의평가점수와발병후 1년이지난시점에서각환자가마지막으로평가한점수의기록을보았다. 운동기능은상지운동기능과균형기능으로나누어본기관에서시행하는상지기능검사및버그균형검사를통해확인을하였다. 상지기능검사는상지의근위부와원위부기능을평가하는검사로어깨 굴곡과외전정도, 손을후두부와등에닿게했을때닿는위치, 공잡기및손으로물건짚기능력, 입방체의운반과페그보드수행능력에따라 0 32점까지점수를받게되며점수가높을수록좋은기능을의미한다. 버그균형검사는균형능력을평가하는검사로크게자세의유지능력, 자발적운동의조절능력, 외부요인에대한반사능력의 3영역으로나누어총 14개의평가항목으로이루어져있으며각항목당 0 4점으로점수를부여하여총 56점이만점인검사로점수가좋을수록좋은균형능력을가졌음을의미한다. 인지기능은 K-MMSE를이용하였으며일상생활동작수행능력은수정바델지수를통해확인을하였다. 또한 6개월시점과마지막기능평가점수의차이를조사하여각기능평가총점의 10% 를기준으로점수가향상또는저하된환자의비율을알아보았다. 이에따라상지기능검사는 4점, 버그균형검사는 6점, K-MMSE 4점, 그리고수정바델지수는 11점이상이기능변화를구분하는기준에해당하였다. 3) 분석및통계뇌졸중발병후 6개월시점과마지막으로평가한시점동안의기능평가점수의비교는대응표본 T검정을이용하였으며 6개월을기준으로 6개월시점에비해마지막으로평가한기능의점수가 10% 이상저하된군을 만성기에기능이저하된군 으로정의하였고정의된군과의무기록을통해확인이된환자의기본정보와상관관계가있는지에대해서이변량상관분석을이용해분석하였다. 통계는 SPSS version 12.0을이용하였고 p값이 0.05 미만일때유의한것으로판단하였다. 결과 1) 일반적특성연구대상 60명중 32명은뇌경색, 28명은뇌출혈이었으며좌측뇌병변은 34명, 우측뇌병변은 21명그외지주막하출혈, 뇌실내출혈및양측의병변이모두있는환자는 5명이었다. 확인이가능하였던 39명중 NIHSS가 0 5 점은 23명 6 13점은 13명, 14점이상은 3명으로확인이되었다. 7명의환자는조사이전에뇌졸중기왕력을가지고있었으며, 7명의환자에서조사기간동안에뇌졸중의재발을보였다. 심장질환은고혈압이 37명으로가장많았고, 외래추적기간동안재활치료를유지한환자의비율이 41.7% 였다 (Table 1). 전체환자에서외래에서각기능평가별로마지막평가가이루어진시점은발병후평균 27
Brain& NeuroRehabilitation:2013; 6: 26~32 23.1 25.8 개월이었다. 2) 상지운동기능의변화 상지기능검사를통하여뇌졸중발생후 6 개월시점과 Table 1. Characteristics of Patients and Possible Predictive Factors of Long-term Outcome (N = 60) Variables n (%) Demographics Age 65 years 14 (23.3) Age <65 years 46 (76.7) Male 33 (55.0) Stroke severity, n (%) (n = 39) NIHSS rating 0 5 23 (59.0) NIHSS rating 6 13 13 (33.3) NHISS rating 14 3 (7.7) Dominant lesion of stroke Left hemisphere 34 (56.7) Right hemisphere 21 (35.0) Others 5 (8.3) Type of stroke Ischemic 32 (53.3) Hemorrhagic 28 (46.7) Recurrent stroke Previous stroke 7 (11.7) Recurrent stroke after this event 7 (11.7) Cardiac problem Hypertension 37 (60.7) Arrhythmia 4 (6.7) Myocardial infarction 2 (3.3) Spasticity Upper extremity 24 (40.0) Lower extremity 10 (16.7) Fall down 2 (3.3) Depression 12 (20.0) Maintain treatment 25 (41.7) 마지막평가시점에서상지운동기능을확인할수있었던환자수는 28명으로관찰기간은평균 23.1개월이었다. 상지기능검사점수의변화는뇌졸중발생후 6개월시점 16.9점, 마지막으로평가한시점의평균값은 19.0점으로통계적으로유의한변화는보이지않았다 (p = 0.068) (Fig. 1). 만성기에상지기능이감소된환자의비율은 10.7% 였으며, 위험인자중에서통계적으로유의하게상관관계를보인변수는없었다 (Table 2). 3) 균형기능의변화 버그균형검사를통하여뇌졸중발생후 6 개월시점과 Fig. 1. Changes of mean value of the upper extremity function, balance, cognitive function, and activities of daily living. The mean duration of final evaluation of MFT, K-BBS, K-MMSE, and K-MBI were 23.1, 23.4, 25.8 and 25.2 months, respectively. MFT: manual function test, K-BBS: Korean version of Berg balance scale, K-MMSE: Korean version of mini mental status examination, K-MBI: Korean version of modified Barthel index. *n showed each number of participants who had evaluated at the two point. Table 2. Results of Bivariate Correlation Analysis between Functional Deficit and Risk factors Variables MFT (n = 28) K-BBS (n = 20) K-MMSE (n = 30) K-MBI (n = 15) Age 60 years.248 (.204).126 (.597).035 (.853).378 (.165) Previous stoke.145 (.462).275 (.241).102 (.590).277 (.317) Recurrent stroke.145 (.462).145 (.541).484* (.007).378 (.165) Hypertension.137 (.487).218 (.355).432* (.017).472 (.075) Cardiac problem.101 (.611).c (.000).247 (.188).189 (.500) Diabetes mellitus.061 (.759).031 (.898).118 (.534).107 (.705) Lower spasticity.138 (.485).327 (.159).035 (.853).200 (.475) Fall down.193 (.325).150 (.527).c (.000).c (.000) Depression.061 (.759).275 (.241).079 (.679).000 (1.000) Maintain treatment.064 (.748).154 (.518).071 (.710).000 (1.000) Values are correlation coefficient (p value)..c: constant. 28
임지훈외 3 인 : 뇌졸중환자에서장기적인기능변화와관련된요인분석 마지막평가시점에서균형기능을확인할수있었던환자수는 20명으로관찰기간은평균 23.4개월이었다. 균형기능변화를확인한결과뇌졸중발생후 6개월시점 45.5 점, 마지막평가시점의평균값은 43.6점으로통계적으로유의한변화는없었다 (p = 0.397) (Fig. 1). 만성기에균형기능이저하된환자의비율은 15% 이었으며, 통계적으로유의하게상관관계를보인변수는없었다 (Table 2). 4) 인지기능의변화 K-MMSE 를통해뇌졸중발생후 6개월시점과마지막평가시점에서인지기능을확인할수있었던환자수는 30명으로관찰기간은평균 25.8개월이었다. 인지기능변화를확인한결과뇌졸중발생후 6개월시점 21.5점, 마지막평가시점의평균값은 23.0점으로통계적으로유의한변화는없었다 (p = 0.257) (Fig. 1). 10% 의환자에서 K-MMSE 점수의저하가나타났으며뇌졸중의재발 (p = 0.007) 과고혈압 (p = 0.017) 이인지기능저하와의미있는관련이있는것으로나타났다. 5) 일상생활동작수행능력의변화수정바델지수를통해뇌졸중발생후 6개월시점과마지막평가시점에서일상생활동작수행능력을확인할수있었던환자수는 15명으로관찰기간은평균 25.2개월이었다. 일상생활동작수행능력의변화를확인한결과뇌졸중발생후 6개월시점 16.9점, 마지막으로평가한시점의평균값은 19.0점으로통계적으로유의한변화는없었다 (p = 0.248) (Fig. 1). 만성기에수정바델지수가저하된환자는 20% 를차지하였으며위험인자와상관관계를분석을한결과통계적으로유의한변수로나타난요인은없었다 (Table 2). 고찰 본연구는뇌졸중발생후장기적인기능의변화를알아보고 6개월이지난만성기뇌졸중환자에서운동기능, 인지기능과일상생활동작수행능력의저하에영향을미치는요인을알아보고하였다. 본연구결과에따르면상지기능평가, 버그균형검사, K-MMSE, 수정바델지수에서모두발병 6개월시점이후추적관찰기간동안유의한변화를보이지않는것으로확인되었다. 그리고뇌졸중후인지기능의감소가나타난환자에서뇌졸중의재발과고혈압이장기적인인지기능저하와상관관계가있는것으로나타났다. 이전연구에따르면뇌졸중후기능적회복의대부분은 Fig. 2. The proportion of the funtionally improved or declined patients according to the funtional domain at the point of final evaluation as compared to the score at the point of 6 months after onset of stroke. MFT: manual function test, K-BBS: Korean version of Berg balance scale, K-MMSE: Korean version of mini mental status examination, K-MBI: Korean version of modified Barthel index, improved: The final score of the scale increased compared to that of 6 months more than 10% of each scale s maximum point, unchanged: The final score of the scale was unchanged compared to that of 6 months, declined: The final score of the scale decreased compared to that of 6 months more than 10% of each scale s maximum point. 발병후 6개월이내에나타나는것으로보고되고있다. 2 상지기능을살펴보면 Broeks 등 12 은 55명의뇌졸중환자를대상으로발병직후와 16주후, 4년후의상지기능을추적관찰한결과대부분의상지기능회복이발병후처음 16주이내에일어났다. 그렇지만 10명의환자에서 Fugl-Meyer score가 16주후에도향상이있었고, 13명의환자에서는상지기능의회복이 16주이후에만일어났다고보고하였다. 본연구에서는 6개월시점과마지막평가시점의상지기능검사결과를비교한결과 3명 (10.7%) 에서기능의저하가있었으며 11명 (39.3%) 은 6개월시점의점수보다더향상된것으로나타났다 (Fig. 2). 뇌졸중후보행장애역시가장흔하게발생하는기능적제한중에하나이다. 3 뇌졸중후보행능력은에너지소비증가, 13 균형을제어하는능력감소, 14 건측하지의근골격계손상 14 등에의해영향을받게되며이동능력의감소를초래하게된다. 15 이전연구에따르면보행기능은뇌졸중발생후 3 6개월까지향상을이루다가그이후에는정체기에접어든다고보고되고있다. 4,5,7,16,17 Olsen 등 18 은 72 명의뇌졸중환자중 95% 에서도발병후 14주이내에개인의최상능력에도달하였다고보고하였다. Andrews등 19 의연구에서도발병후 2주와 8주, 6개월, 1년에보행능력을비교한결과 6개월이후에는유의한향상을보이지 29
Brain& NeuroRehabilitation:2013; 6: 26~32 않았고, Skilbeck 등 5 이 3개월, 6개월, 12개월에보행기능을평가한결과도같은결과를보였다. Michael 등 20 은보행기능이버그균형점수와매우밀접한연관관계가있다고발표하였다. 본연구에서는보행기능의한측면으로버그균형검사를조사하였는데발병후 6개월이후에는유의한변화는없어이전의연구와같은결과를나타냈다. 뇌졸중후인지기능장애는 11.6% 에서 56.3% 까지매우다양하게발생하는것으로보고하였다. 21-25 Patel 등 26 은뇌졸중후 MMSE 점수가 24점미만으로나타나는인지장애의비율이뇌졸중발생후 3개월시점에 39%, 1년후 35%, 2년후 30%, 3년후 32% 인것으로보고하였고인지장애는흡연, 편측무시, 우측뇌병변과관련이있었다고발표하였다. 그리고 Liman 등 27 은 MMSE 점수가 24 점미만으로나타나는인지장애의비율이 3개월, 1년, 3 년시점에각각 15%, 13%, 12% 로나타났으며뇌졸중의심한정도와나이, 당뇨가인지장애와관련이있었다고발표하였다. 그리고이연구에서뇌졸중후 3개월에인지장애가있는것으로평가되었던환자중 31% 에서 3년후 24점이상으로회복되었다고발표하였다. 그리고 Ser 등 28 은이전에치매가없었던뇌졸중환자를대상으로 2년간경과관찰을한결과 78.2% 에서인지변화가없었으며 14% 에서는인지기능의저하가그리고 7.8% 에서는인지기능의향상이관찰되었는데환자의나이, 뇌졸중이전의인지기능저하, 입원시이완기혈압, 입원중저혈압의기왕력, 다약제투여가인지기능저하와관련이있다고하였다. 본연구에서는 K-MMSE 점수가평균 25.8개월동안 6개월시점, 마지막으로평가한시점간에차이가없는것으로나타났다. 본연구에서주목할만한것은고혈압과뇌졸중의재발이인지기능감소와관련이있는것으로확인되었다는점이다. 이전의연구에서도고혈압환자와정상혈압환자를대상으로인지평가를비교한결과고혈압이있는환자에서반응시간, 장단기시청각기억력, 실행력등에서저하된것으로보고하였으며 29 40 69세의중년을대상으로한연구에서 12년의경과관찰기간동안고혈압을가진환자에서실행기능과시각운동적인능력이떨어지는결과를보였다. 30 이밖에도고혈압이인지기능저하에영향을끼친다고많은연구에서보고하였으며이는혈압의자동조절 (autoregulation) 이 60 150 mmhg 범위의평균전신혈압 (mean systemic pressure) 의범위내에서유지가되다가고혈압과저혈압의상태에서는이러한자동조절기능의이상을초래하게되고이로인해뇌로전달되는혈류에장애를일으키게되면서인지장애를일으키는것으로알려져있다. 31 그러므로뇌졸중의재발을예방하고혈압을조절하는것이장기적인인지 기능저하를막는데매우중요할것으로생각된다. 일상생활능력은 Jorgensen 등 1 에따르면뇌졸중후 95% 에서 12.5주이내최대기능에도달하였으며 80% 에서는발병후 6주이내에최대일상생활동작수행능력에들어선다고보고하였다. 1,32-35 Hankey 등 36 은 129명의뇌졸중환자를대상으로 5년간의수정바델지수를확인한결과 36% 에서경과관찰기간동안기능의저하가발생하였고나이와기저장해, 편마비, 뇌졸중재발이예후에영향을끼친다고발표하였다. 36 그리고 Dhamoon 등 37 은 5년간의뇌졸중환자를대상으로수정바델지수를추적관찰한결과해마다유의하게일상생활동작수행능력이저하되는것을확인하였다. 본연구에서는평균 25.2개월동안수정바델지수점수변화가 6개월시점이후의만성기에유의한차이를보이지않는것으로확인되어 Dhamoon 등의결과와다른결과를나타냈다. 6개월시점과마지막평가시점의비교가가능하였던 15명의환자중기능의저하가일어난환자는 3명 (20.0%), 일상생활기능의향상이일어난환자는 5명 (33.3%) 인것으로나타나 Hankey 등이제시하였던 36% 보다낮은인지기능저하비율을보였다 (Fig. 2). 이번연구는장기간외래에서경과를관찰한뇌졸중환자를대상으로운동및인지기능, 일상생활동작수행능력등다양한측면의기능이어떤변화를보이는지에대해서함께알아보았다는데에의의가있다. 그렇지만본연구에서후향적으로의무기록에근거하여환자의정보를조사함으로써자료가누락되어제외된환자로인해연구대상의수가적었다는점과각환자마다기능평가의시점이일치하지않았다는점은큰제약으로생각된다. 그리고외래추적관찰이가능하였던환자를대상으로하였기때문에상대적으로일상생활동작수행이어느정도가능한환자가대상에포함되어이로인한표본선택편의 (selection bias) 가결과에영향을끼쳤을것으로생각된다. 그리고이번연구에서는다양한기능의변화를보기위해상대적으로간단한검사방법을이용하였는데이또한간단한평가지표로실질적인기능의정도를평가하는데많은제약이있을것으로생각된다. 따라서추후에는좀더다양한평가방법을통하여구체적인기능을평가하는연구가이루어져야한다고생각된다. 향후뇌졸중후장기간의기능의변화와예후에영향을끼칠수있는요인을알아보기위해서는다기관에서많은환자를대상에포함하는전향적인연구가이루어져야할것으로생각된다. 30
임지훈외 3 인 : 뇌졸중환자에서장기적인기능변화와관련된요인분석 결론 만성뇌졸중환자에서상지운동기능, 균형기능, 인지기능과일상생활동작수행능력은장기간경과관찰을하는동안전반적으로유의한변화가없었다. 그렇지만뇌졸중의재발과고혈압이인지기능의감소에있어서영향을끼치는예후변수로나타나뇌졸중의재발을예방하고혈압을조절하는것이장기적인인지기능의저하를막는데매우중요할것으로생각된다. 참고문헌 1) Jorgensen HS, Nakayama H, Raaschou HO, Vivelarsen J, Stoier M, Olsen TS. Outcome and time-course of recovery in stroke. Part. II. time-course of recovery - the Copenhagen stroke study. Arch Phys Med Rehab. 1995;76:406-412 2) Duncan PW, Goldstein LB, Matchar D, Divine GW, Feussner J. Measurement of motor recovery after stroke - outcome assessment and sample-size requirements. Stroke. 1992;23: 1084-1089 3) Bohannon RW, Andrews AW, Smith MB. Rehabilitation goals of patients with hemiplegia. Int J Rehabil Res. 1988; 11:181-183 4) Wade DT, Wood VA, Hewer RL. Recovery after stroke-the first 3 months. J Neurol Neurosur Ps. 1985;48:7-13 5) Skilbeck CE, Wade DT, Hewer RL, Wood VA. Recovery after stroke. 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