臺灣博碩士論文加值系統

目的：本研究有兩大目標，首先為編製一套容易使用且具有信效度的評估工具，用以測量阿茲海默氏症 (Alzheimer’s disease, AD) 患者的認路障礙 (topographical disorientation, TD) 症狀。第二則為評估其迷路初發率 (getting lost incidence, GL incidence)、再發率 (GL recurrence) 及相關風險因子。
方法：邀請仍居住於社區之輕度至中度 AD 患者及其家屬參與研究，蒐集患者的人口學變項、日常生活型態與外出限制、迷路事件、神經心理功能 (Cognitive Ability Screening Instrument, CASI ＆ Mini-Mental Status Examination, MMSE)，並檢驗自編之日常生活認路能力問卷 (Questionnaire of Everyday Navigational Ability, QuENA) 的信效度。QuENA 的構念包括地標與街景失認 (landmark and scene agnosia)、自我中心失定向 (egocentric disorientation)、注意力缺損 (inattention) 與頭向失定向 (heading disorientation)。信度指標採內部一致性係數與重測信度，建構效度採用驗證性因素分析檢驗資料是否符合假設構念，效標效度則評估 QuENA 對迷路事件的預測力。在基線期 2.5 年後，有 185 AD 患者及其家屬完成追蹤期評估，其中有 90 位未曾發生過迷路事件 (Group A)；95 位已在發病後發生過一次以上的迷路事件 (Group B)。
結果：QuENA 在患者自評與家屬評估均具有良好的信度，但患者自評的建構效度與預測效度均較差。185 位完成追蹤期評估者中，有 148 (80%) 位以面談完成，另外 37 (20%) 位以電訪完成。在 2.5 年間，Group A 中有 33.3% 初次發生迷路事件 (GL incidence)，Group B 中則有 40.0% 迷路再次發生 (GL recurrence)。Multiple logistic regression 分析發現在 QuENA 中的注意力缺損與 CASI 中的定向感分數可預測迷路的初發。另一方面，在 Group B 中，年齡較輕與未將自己限制在安全範圍內的患者，其迷路再發風險較高。
結論：QuENA 是個容易施測且具有信效度的認路障礙評估工具，可用於評估 AD 患者的迷路風險。在迷路預測因子部份，神經心理功能中的「定向感」與 QuENA 中的「注意力缺損」可預測尚未迷路的 AD 患者的迷路風險，然而患者若已迷路過，其預測因子便有相當大的改變，對於年齡較輕且無安全範圍的患者而言，家屬需特別注意其迷路再發之風險。除此之外，迷路亦可能是 AD 亞型的行為表現之一，迷路者的退化模式與無迷路經驗者不同。

Objectives: To develop a feasible, reliable, and valid instrument to evaluate the topographical disorientation (TD) symptoms of the patients with Alzheimer's disease (PwAD) and to monitor the risk factors for getting lost (GL) events and to determine the incidence and recurrence rates of it.
Methods: A longitudinal study of community-dwelling PwAD was performed between April 2009 and March 2012 and encompassing baseline and a 2.5-year follow-up examination. The baseline information was used to establish the reliability and validity of the Questionnaire of Everyday Navigational Ability (QuENA). We focused on new GL events and the associated factors from their demographic data and daily functions by interview, cognitive functions by CASI and MMSE, and behaviors by the QuENA. The study population consisted of 185 PwAD and their co-habitant collaterals. At the baseline, 95 had ever experienced GL (Group B), while and the remaining 90 (Group A) had not.
Results: In the baseline evaluation, the construct validity of QuENA, confirmatory factor analysis showed that the caregiver version of the QuENA fits the proposed TD model well but the patient version does not. Regarding the internal consistency, the Cronbach’s α of the caregiver version was 0.91 and that for the patient version was 0.87. In the follow-up evaluation, 148 (80%) of the participants were interviewed by face to face, and 37 (20%) by telephone; no difference was detected between them in any variable of interest. After a 2.5-year period, 33.3% in the Group A developed GL (incidence) and 40% in the Group B developed GL (recurrence). Multiple logistic regression analysis revealed that inattention on the QuENA and orientation on the CASI had the independent effect on incidence, while being younger and the absence of safety range waved alarm for recurrence. Moreover, during the 2.5 years, PwAD with GL incidence deteriorated more in mental manipulation on CASI than those without.
Conclusions: Cognitive assessment and the QuENA can alarm for the risk of GL incidence. We suggest that once GL occurs, the collaterals of PwAD must take the responsibilities to prevent from the recurrence, in particular for younger patients. In addition, GL may be a behavioral manifestation for subtypes of AD.

第一章 緒論........................................................................................1
第一節、研究背景...................................................................................1
第二節、阿茲海默氏症............................................................................... 3
壹、臨床特徵.................................................................................... 3
貳、病理變化.....................................................................................3
參、AD 的異質性...................................................................................3
第三節、迷路與地域失定向.............................................................................5
壹、認知功能健康者的迷路行為.....................................................................5
貳、地域失定向的歷史演變............................................................................5
參、發生在熟悉環境的 TD 症狀...................................................................8
肆、地域失定向與迷路行為的關係...............................................................10
第四節、阿茲海默氏症患者的地域失定向症狀...............................................12
壹、個案研究..................................................................................................12
貳、團體研究..................................................................................................13
第五節、阿茲海默氏症患者的迷路行為...........................................................15
壹、AD 患者的迷路盛行率...........................................................................15
貳、AD 患者迷路行為的特質與定義...........................................................15
參、迷路相關風險因子...................................................................................16
第二章 研究目的與研究內容..............................................................................18
第一節、子研究一：地域失定向評估工具編製..............................................19
壹、研究目的與研究假設..............................................................................19
貳、研究方法..................................................................................................20
一、研究參與者...........................................................................................20
二、日常生活認路能力問卷之設計理念與評估重點...............................21
三、迷路行為評估.......................................................................................24
四、統計分析...............................................................................................25
參、結果分析..................................................................................................26
一、研究參與者..........................................................................................26
二、迷路行為..............................................................................................28
三、QuENA 信效度建立...........................................................................29
肆、討論..........................................................................................................39
一、QuENA 的信效度...............................................................................39
二、AD 患者的迷路行為..........................................................................41
第二節、子研究二：AD 患者之迷路風險因子...............................................43
壹、研究目的與研究假設...............................................................................43
貳、研究方法..................................................................................................44
一、研究參與者..........................................................................................44
二、研究測量..............................................................................................44
三、統計分析...............................................................................................47
參、結果分析...................................................................................................49
一、迷路初發與再發的相關風險因子.......................................................49
二、基線期與追蹤期之間的變化...............................................................66
肆、討論...........................................................................................................82
一、迷路初發與再發的預測因子...............................................................82
二、神經心理功能退化模式與迷路行為...................................................84
三、QuENA 評估的變化...........................................................................86
第三章 結論與建議.......................................................................................88
第一節、家屬扮演的角色...................................................................................88
第二節、研究優勢與限制...................................................................................89
第三節、結論...........................................................................................90
參考文獻................................................................................................91
附錄
附錄 I 參與者同意書....................................................................................99
附錄 II NINCDS-ADRDA 診斷準則...........................................................101
附錄 III DSM-IV-TR 之阿茲海默氏症診斷標準.......................................103
附錄 IV日常生活認路能力問卷....................................................................104 

劉景寬, 戴志達, 林瑞泰, ＆ 賴秋蓮. (2000). 台灣失智症的流行病學. 應用心理研究(7), 157-169.
內政部戶政司（2009）。歷年人口數、年增加率、育齡婦女數、總生育率、出生、性別比例、未婚男女性人口數、老年人口百分比、扶養比及國際戶籍遷徙統計表。檢自：http://www.ris.gov.tw/ch4/static/yhsb09700.xls
Aguirre, G. K., ＆ D'Esposito, M. (1999). Topographical disorientation: a synthesis and taxonomy. Brain, 122(9), 1613-1628.
Algase, D. L., Son, G. R., Beel-Bates, C., ＆ Song, J. (2007). Initial psychometric evaluation of the wayfinding effectiveness scale. Western Journal of Nursing Research, 29(8), 1015-1032.
Algase, D. L. (2006). What's new about wandering behaviour? An assessment of recent studies. Int J Older People Nurs, 1(4), 226-234.
Algase, D. L., Moore, D. H., Vandeweerd, C, ＆ Gavin-Dreschnack, D. J. (2007). Mapping the maze of terms and definitions in dementia-related wandering. Aging Ment Health, 11(6), 686-698.
Antonakos, C. L. (2004). Compensatory wayfinding behavior in topographic disorientation from brain injury. J Environ Psychol, 24(4), 495-502.
Bagozzi, R. P., ＆ Yi, Y. (1988). On the evaluation of structural equation models. Journal of the academy of marketing science, 16(1), 74-94.
Ballard, C. G., Mohan, R. N. C., Bannister, C., Handy, S., ＆ Patel, A. (1991). Wandering in dementia sufferers. International journal of geriatric psychiatry, 6(8), 611-614.
Barrash, J. (1998). A historical review of topographical disorientation and its neuroanatomical correlates. J Clin Exp Neuropsyc, 20(6), 807-827.
Benton, A. L. (1969). Disorders of spatial orientation. Handbook of clinical neurology, 3, 212-228.
Binetti, G., Magni, E., Padovani, A., ＆ Cappa, S. F. (1993). Neuropsychological heterogeneity in mild Alzheimer's disease. Dementia, 4(6), 321-326.
Bottini, G., Cappa, S., Geminiani, G., ＆ Sterzi, R. (1990). Topographic disorientation--a case report. Neuropsychologia, 28(3), 309-312.
Bowen, M. E., McKenzie, B., Steis, M., ＆ Rowe, M. A. (2011). Prevalence of and antecedents to dementia-related missing incidents in the community. Dement Geriatr Cogn Disord, 31(6), 406-412.
Braak, E., Griffing, K., Arai, K., Bohl, J., Bratzke, H., ＆ Braak, H. (1999). Neuropathology of Alzheimer's disease: what is new since A. Alzheimer? Eur Arch Psychiatry Clin Neurosci, 249(9), 14-22.
Braak, H., ＆ Braak, E. (1995). Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging, 16(3), 271-282.
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., et al. (2005). Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. Journal of Neuroscience, 25(34), 7709.
Burgess, N., Trinkler, I., King, J., Kennedy, A., ＆ Cipolotti, L. (2006). Impaired allocentric spatial memory underlying topographical disorientation. Rev Neurosci, 17(1-2), 239-251.
Cammalleri, R., Gangitano, M., D'Amelio, M., Raieli, V., Raimondo, D., ＆ Camarda, R. (1996). Transient topographical amnesia and cingulate cortex damage: a case report. Neuropsychologia, 34(4), 321-326.
Chiu, YC, Algase, D, Whall, A, Liang, J, Liu, HC, Lin, KN, ＆ Wang, PN. (2004). Getting lost: directed attention and executive functions in early Alzheimer's disease patients. Dement Geriatr Cogn Disord, 17(3), 174-180.
Chui, H. C., Teng, E. L., Henderson, V. W., ＆ Moy, A. C. (1985). Clinical subtypes of dementia of the Alzheimer type. Neurology, 35(11), 1544-1544.
Cushman, L. A., Stein, K., ＆ Duffy, C. J. (2008). Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality. Neurology, 71(12), 888-895.
de Leon, M. J., Potegal, M., ＆ Gurland, B. (1984). Wandering and parietal signs in senile dementia of Alzheimer's type. Neuropsychobiology.
DeRenzi, E. (1982). Disorders of spatial exploration and processing: Wiley.
Dudchenko, P. A. (2010). Why People Get Lost. New York: Oxford University Press Inc.
Ecklund-Johnson, E., ＆ Torres, I. (2005). Unawareness of deficits in Alzheimer's disease and other dementias: operational definitions and empirical findings. Neuropsychology Review, 15(3), 147-166.
Giannakopoulos, P., Gold, G., Duc, M., Michel, J. P., Hof, P. R., ＆ Bouras, C. (2000). Neural substrates of spatial and temporal disorientation in Alzheimer's disease. Acta neuropathologica, 100(2), 189-195.
Grossi, D., Fasanaro, A. M., Cecere, R., Salzano, S., ＆ Trojano, L. (2007). Progressive topographical disorientation: a case of focal Alzheimer's disease. Neurol Sci, 28(2), 107-110.
Grusser, O., ＆ Landis, T. (1991). Getting lost in the world: Topographical disorientation and topographical agnosia. Vision and Visual Dysfunction, 12, 411-430.
Henderson, V. W., Mack, W., ＆ Williams, B. W. (1989). Spatial disorientation in Alzheimer's disease. Archives of Neurology, 46(4), 391.
Hendrie, H. C. (1998). Epidemiology of dementia and Alzheimer's disease. The American Journal of Geriatric Psychiatry.
Hirono, N., Mori, E., Ishii, K., Ikejiri, Y., Imamura, T., Shimomura, T., et al. (1998). Hypofunction in the posterior cingulate gyrus correlates with disorientation for time and place in Alzheimer’s disease. J Neurol Neurosurg Psychiatry, 64(4), 552-554.
Hort, J., Laczó, J., Vyhnálek, M., Bojar, M., Bureš, J., ＆ Vlček, K. (2007). Spatial navigation deficit in amnestic mild cognitive impairment. Proc Natl Acad Sci USA, 104(10), 4042-4047.
Hu, L., ＆ Bentler, P. M. (1999). Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives. Structural Equation Modeling: A Multidisciplinary Journal, 6(1), 1-55.
Huang, C., Wahlund, L. O., Svensson, L., Winblad, B., ＆ Julin, P. (2002). Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurol, 2(1), 9-15.
Hwang, J. P., Yang, CH., Tsai, S.J., ＆ Liu, K.M. (1997). Behavioural disturbances in psychiatric inpatients with dementia of the Alzheimer's type in Taiwan. International journal of geriatric psychiatry, 12(9), 902-906.
Iaria, G., Bogod, N., Fox, C.J., ＆ Barton, J.J.S. (2009). Developmental topographical disorientation: Case one. Neuropsychologia, 47(1), 30-40.
Jellinger, K.A. (2012). Neuropathological subtypes of Alzheimer’s disease. Acta neuropathologica, 123(1), 1-2.
Jheng, S. S., ＆ Pai, M. C. (2009). Cognitive map in patients with mild Alzheimer's disease: A computer-generated arena study. Behavioural Brain Research, 200(1), 42-47.
Joreskog, K. G. (1993). Testing structural equation models. Testing structural equation models, 294, 316.
Kalbe, E., Salmon, E., Perani, D., Holthoff, V., Sorbi, S., Elsner, A., et al. (2005). Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment. Dement Geriatr Cogn Disord, 19(5-6), 349-356.
Kwok, T. C. Y., Yuen, K. S. L., Ho, F. K. Y., ＆ Chan, W. M. (2010). Getting lost in the community: a phone survey on the community‐dwelling demented people in Hong Kong. Int J Geriatr Psychiatry, 25(4), 427-432.
Lawton, C. A. (1994). Gender differences in way-finding strategies: Relationship to spatial ability and spatial anxiety. Sex Roles, 30(11), 765-779.
Lawton, C. A., Charleston, S. I., ＆ Zieles, A. S. (1996). Individual-and gender-related differences in indoor wayfinding. Environment and Behavior, 28(2), 204-219.
Lee, Y. T., ＆ Pai, M. C. (2012). Recognition of personally familiar scenes in patients with very mild Alzheimer's disease: Effects of spatial frequency and luminance. J Alzheimers Dis, 29(2), 441-448.
Leicht, H., Berwig, M., ＆ Gertz, H. J. (2010). Anosognosia in Alzheimer's disease: The role of impairment levels in assessment of insight across domains. Journal of the International Neuropsychological Society, 16(03), 463-473.
Levine, D. N., Warach, J., ＆ Farah, M. (1985). Two visual systems in mental imagery: Dissociation of what and where in imagery disorders due to bilateral posterior cerebral lesions. Neurology, 35(7), 1010-1018.
Lezak, M. D. (2004). Neuropsychological assessment: Oxford University Press, USA.
Liu, C. K. (2006). The epidemiology of dementia in Taiwan. Acta Neurologica Taiwanica, 15(1), 51.
Maddock, R. J., Garrett, A. S., ＆ Buonocore, M. H. (2001). Remembering familiar people: the posterior cingulate cortex and autobiographical memory retrieval. Neuroscience, 104(3), 667-676.
McShane, R., Gedling, K., Keene, J., Fairburn, C., Jacoby, R., ＆ Hope, T. (1998). Getting lost in dementia: a longitudinal study of a behavioral symptom. Int Psychogeriatr, 10(03), 253-260.
Migliorelli, R., Teson, A., Sabe, L., Petracca, G., Petracchi, M., Leiguarda, R., ＆ Starkstein, S. E. (1995). Anosognosia in Alzheimer's disease: a study of associated factors. Journal of Neuropsychiatry and Clinical Neurosciences, 7(3), 338.
Murray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., ＆ Dickson, D. W. (2011). Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. The Lancet Neurology, 10(9), 785–796.
Pai, M. C., ＆ Jacobs, W. J. (2004). Topographical disorientation in community-residing patients with Alzheimer's disease. Int J Geriatr Psychiatry, 19(3), 250-255.
Pai, M. C., ＆ Jacobs, W. J. (2008). Navigational disorders patients with Alzheimer's disease. In A. P. Chan (Ed.), Alzheimer's Disease Research Trends (pp. 275-288). Hauppauge Nova Biomedical Books.
Pai, M. C., Lee, C. C., Yang, Y. C., Lee, Y. T., Chen, K. C., Lin, S. H., et al. (2012). Development of a questionnaire on everyday navigational ability to assess topographical disorientation in Alzheimer’s disease. Am J Alzheimers Dis Other Demen, 27(1), 65-72.
Pai, M. C., ＆ Yang, Y. C. (in press). Impaired translation of spatial representation in young onset Alzheimer's disease patients. Curr Alzheimer Res.
Passini, R., Rainville, C., Marchand, N., ＆ Joanette, Y. (1995). Wayfinding in dementia of the Alzheimer's type: Planning abilities. J Clin Exp Neuropsychol, 17(6), 820-832.
Petersen, R. C. (1998). Clinical subtypes of Alzheimer’s disease. Dementia and geriatric cognitive disorders, 9(3), 16-24.
Rainville, C., Joubert, S., Felician, O., Chabanne, V., Ceccaldi, M., ＆ Peruch, P. (2005). Wayfinding in familiar and unfamiliar environments in a case of progressive topographical agnosia. Neurocase, 11(5), 297-309.
Rainville, C., Passini, R., ＆ Marchand, N. (2001). A multiple case study of wayfinding in dementia of the Alzheimer type: decision making. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn, 8(1), 54-71.
Rankin, K. P., Mucke, L., Miller, B. L., ＆ Gorno-Tempini, M. L. (2007). Spatial cognition and the human navigation network in AD and MCI. Neurology, 69(10), 986-997.
Rosenbaum, R. S., Gao, F., Richards, B., Black, S. E., ＆ Moscovitch, M. (2005). “Where to? Remote memory for spatial relations and landmark identity in former taxi drivers with Alzheimer's disease and encephalitis. J Cogn Neurosci, 17(3), 446-462.
Rosenbaum, R. S., Priselac, S., Kohler, S., Black, S. E., Gao, F., Nadel, L., ＆ Moscovitch, M. (2000). Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions. Nat Neurosci, 3, 1044-1048.
Rowe, M. A. (2003). People with dementia who become lost: preventing injuries and death. AJN The American Journal of Nursing, 103(7), 32.
Rowe, M. A, Vandeveer, SS, Greenblum, CA, List, CN, Fernandez, RM, Mixson, NE, ＆ Ahn, HC. (2011). Persons with dementia missing in the community: Is it wandering or something unique? BMC Geriatrics, 11(1), 28-36.
Schnider, A., Ptak, R., von Däniken, C., ＆ Remonda, L. (2000). Recovery from spontaneous confabulations parallels recovery of temporal confusion in memory. Neurology, 55(1), 74-83.
Schnider, A. (2000). Spontaneous confabulations, disorientation, and the processing of now. Neuropsychologia, 38(2), 175-185.
Shiino, A., Watanabe, T., Maeda, K., Kotani, E., Akiguchi, I., ＆ Matsuda, M. (2006). Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and a unique pattern for early onset disease. NeuroImage, 33(1), 17-26.
Skelton, R. W., Bukach, C. M., Laurance, H. E., Thomas, K. G. F., ＆ Jacobs, J. W. (2000). Humans with traumatic brain injuries show place-learning deficits in computer-generated virtual space. Journal of clinical and experimental neuropsychology, 22(2), 157-175.
Starkstein, S. E., Jorge, R., Mizrahi, R., Adrian, J., ＆ Robinson, R. G. (2007). Insight and danger in Alzheimer's disease. European journal of neurology, 14(4), 455-460.
Sugiura, M., Shah, N. J., Zilles, K., ＆ Fink, G. R. (2005). Cortical representations of personally familiar objects and places: functional organization of the human posterior cingulate cortex. J Cogn Neurosci, 17(2), 183-198.
Teng, E. L., Lin, K. N., Chou, P., Fuh, J. L., Wang, S. J., ＆ Liu, H. C. (1994). The Cognitive Abilities Screening Instrument and preliminary findings of its Chinese version, CASI-2.0. Chinese J of Clin Psy, 2, 69-73.
Tu, M. C., ＆ Pai, M. C. (2006). Getting lost for the first time in patients with Alzheimer's disease. Int Psychogeriatr, 18(03), 67-70.
Uc, E. Y., Rizzo, M., Anderson, S. W.,＆ Shi, Q. (2004). Driver route-following and safety errors in early Alzheimer disease. Neurology, 63(5), 832-837.
Walker, A. E., Livingston, G., Cooper, C. A., Katona, C. L. E., ＆ Kitchen, G. L. (2006). Caregivers’ experience of risk in dementia: The LASER-AD Study. Aging Ment Health, 10(5), 532-538.
Weniger, G., Ruhleder, M., Lange, C., Wolf, S., ＆ Irle, E. (2010). Egocentric and allocentric memory as assessed by virtual reality in individuals with amnestic mild cognitive impairment. Neuropsychologia, 49(3), 518-527.
Wenk, G. L. (2003). Neuropathologic changes in Alzheimer's disease. Journal of Clinical Psychiatry, 64, 7-10.