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研究生:范英琦
研究生(外文):Ying-Chi Fan
論文名稱:老年癲癇病人的腦部類澱粉蛋白沈積
論文名稱(外文):Brain beta-amyloid burden in elderly with epilepsy
指導教授:周明智周明智引用關係辛裕隆辛裕隆引用關係
指導教授(外文):Ming-Chih ChouMing-Chih Chou
口試委員:闕河鳴
口試委員(外文):Herming Chiueh
口試日期:2020-06-22
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:51
中文關鍵詞:老年癲癇類澱粉蛋白
外文關鍵詞:epilepsybeta amyloid
DOI:10.6834/csmu202000134
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研究目的:
根據現有研究顯示,認知功能障礙(CI)與阿茲海默症(AD)和老年癲癇(EE)的相關性偏高,臨床上最常見的兩大老年癲癇病因分別為腦血管疾病(CVD)和神經退化性疾病(NDD),在兩個臨床上最常見的老年癲癇病因中,腦部核磁共振(Brain MRI ) 可以幫助我們精準的診斷腦血管疾病,而神經退化性疾病如最常見的阿茲海默症卻一直缺乏準確的影像診斷工具,直到近幾年腦部類澱粉正子攝影(FBB PET)的問世,才讓我們有客觀影像工具來診斷阿茲海默症,因此我們想藉由腦部類澱粉蛋白正子攝影來了解老年癲癇病人其腦部類澱粉蛋白的表現,近一步了解老年癲癇和退化性神經疾病的關聯性。
研究方法及資料:
本研究對於目前於中山醫學大學附設醫院追蹤與治療,且年齡超過45歲以上的癲癇病人,排除不符合收案條件的病人,依有無腦部結構病變者分為兩組,將此兩組病人進行腦部類澱粉影像學檢測,觀察其影像學上的特色。
研究結果:
老年癲癇患者腦部類澱粉沈積影像陽性率,遠大於正常老年人,且另發現三個腦部結構病變位置和腦波異常放電區及臨床癲癇表現明顯不符的病人,其腦部類澱粉蛋白沈積影像皆呈現陽性。
結論與建議:
(一) 對於老年癲癇的病人,腦部類澱粉沈積影像陽性率高於正常老年人,這暗示我們老年癲癇發作和神經退化性疾病或是老化的腦部病生理變化相關性可能遠高於我們以往的認知。
(二) 腦部結構病變處和臨床癲癇表現或是癲癇腦波產生區明顯不同的老年癲癇病人,對於查無其他明顯癲癇病因之病人,建議可安排腦部類澱粉正子攝影檢查,釐清該病人癲癇發作是否為神經退化性疾病臨床前期症狀或是神經退化性疾病所導致。
Study purposes
According to current research, elder patients with epilepsy have higher incidence of cognitive dysfunction and Alzheimer's disease. Vascular disease and neurodegenerative disease are the two most common causes of elder epilepsy in the clinic. Brain Magnetic Resonance Imaging (MRI) can help us accurately diagnose cerebrovascular diseases. However, there was no accurate imaging tool to diagnose Alzheimer's disease until the advent of brain amyloid photography (18F-florbetaben Amyloid PET, FBB) in recent years. We have perfect Imaging tools to diagnose Alzheimer's disease now. We also can verify the correlation between elderly epilepsy and neurodegenerative disease by this image tool. Therefore, we want to use brain amyloid positron photography to understand the brain amyloid burden of elderly epilepsy patients.
Methods:
Our study includes patients with epilepsy older than 45 years old who still follow up at Chung- Shan Medical University Hospital. According to the presence or absence of brain structural lesions, they are divided into two groups. The two groups of patients were complete brain amyloid PET.
Result:
The positive rate of brain amyloid deposition in elderly patients with epilepsy is much higher than elderly people without epilepsy. There were three patient’s clinical epilepsy semiology that was obvious, not correlated to brain structural lesion location in MRI. And those three patient Amyloid PET findings were positive.
Conclusion:
(1) For elderly patients with epilepsy, the positive rate of brain amyloid deposition is higher than that of normal elderly people. It may indicate the higher correlation between the elderly patient with epilepsy and neurodegenerative diseases

(2) If there were no other obvious epilepsy etiology. We recommend complete Amyloid PET when elderly epilepsy patients whose brain structural lesions location is significantly not correlated to clinical epilepsy semiology.
目錄
謝 誌 (致謝) ---------------------------------------------------------------II
中文摘要--------------------------------------------------------------------IV
英文摘要--------------------------------------------------------------------VI
第一章 緒論
第一節 研究背景與動機----------------------------------------------------------1
第二節 研究目的---------------------------------------------------------------3
第二章 文獻探討
第一節 老年癲癇病人------------------------------------------------------------4
第二節 腦部乙型澱粉樣蛋白相關疾病------------------------------------------------7
第三節 類澱粉蛋白正子攝影------------------------------------------------------12
第三章 研究設計
第一節 研究假設--------------------------------------------------------------16
第二節 研究對象--------------------------------------------------------------17
第三節 研究工具--------------------------------------------------------------18
第四節 研究流程--------------------------------------------------------------19
第四章 研究結果與分析
第一節 描述性統計分析---------------------------------------------------------20
第二節 三個別案例------------------------------------------------------------21
第五章 討論-------------------------------------------------------------------23
第六章 結論與建議
第一節 研究假設之結論---------------------------------------------------------26
第二節 研究限制--------------------------------------------------------------28
第三節 研究建議-------------------------------------------------------------29-
參考文獻---------------------------------------------------------------------30
表目錄

附表一 中風後癲癇的定義-------------------------------------------------------33
附表二 2018 NIA-AA阿茲海默症相關研究標準生物標記-----------------34
附表三 2018 NIA-AA阿茲海默症相關研究標準生物標記和臨床症狀-35
附表四 中山醫學大學目前使用的核磁共振規格---------------------------36
附表五 腦皮質區域Neuraceq藥劑影像攝取定義-------------------------37
附表六 腦部乙型類澱粉蛋白神經炎斑塊沈積影像評分定義-----------38

圖目錄
附圖一 整個生命週期中癲癇的發病率和患病率--------------------------39
附圖二 人的前類澱粉蛋白質(APP)蛋白水解途徑------------------------40
附圖三 阿茲海默症動態生物標誌物假想模型-----------------------------41
附圖四 類澱粉蛋白正子攝影圖像評估--------------------------------------42
附圖五 研究流程圖----------------------------------------------------------------43
附圖六 中山醫學大學附設醫院癲癇病人年齡分佈圖-------------------44
附圖七 中山醫學大學附設醫院年齡超過45歲以上癲癇病人年齡分佈圖-------------------------------------------------------------------------------------45
附圖八 癲癇病人發生癲癇的年紀---------------------------------------------46
附圖九 不同組別腦部類澱粉正子攝影施作人數和陽性率-------------47
附圖十 實驗流程圖,各階段人數分佈圖--------------------------------------48
附圖十一 案例一 腦部核磁共振與類澱粉正子攝影影像---------------49
附圖十二 案例二 腦部核磁共振與類澱粉正子攝影影像---------------50
附圖十三 案例三 腦部核磁共振與類澱粉正子攝影影像---------------51
1. Clifford R.JackJr.aDavid A.BennettbKajBlennowc. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer's & Dementia. Volume 14, Issue 4, April 2018, Pages 535-562
2. Author links open overlay panelRani A.SarkisaKim C.Willmenta. Late-onset unexplained epilepsy: What are we missing? Epilepsy & Behavior. Volume 99, October 2019, 106478
3. ArjuneSenFRCPa ,ProfNathalieJetteFRCPCb. Epilepsy in older people. Volume 395, Issue 10225, 29 February 6 March 2020, Pages 735-748
4. J.CloydaW.HauserbA.TownecR.Ramsayd. Epidemiological and medical aspects of epilepsy in the elderly. Epilepsy Research Volume 68, Supplement 1, January 2006, Pages 39-48.
5. Author links open overlay panelJ.CloydaW.Hauserb. Epidemiological and medical aspects of epilepsy in the elderly. Epilepsy Research Volume 68, Supplement 1, January 2006, Pages 39-48
6. Diane da Costa Miranda1 and Sonia Maria Dozzi Brucki2. . Neuromolecular medicine 12(1):71-7 · July 2009 Epileptic Seizures in AD Patients Dement Neuropsychol. 2014 Jan-Mar; 8(1): 66–71.
7. C Costa, M Romoli, C Liguori. Alzheimer's disease and lateonset epilepsy of unknown origin: two faces of beta amyloid pathology. Neurobiology of Aging .Volume 73, January 2019, Pages 61-67 January 2019, Pages 61-67
8. Guo-Fang Chen 1, Ting-Hai Xu 1. Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development.Acta Pharmacol. 2017 Sep;38(9):1205-1235.
9. Reisa A. Sperling, MD1,2; Michael C. Donohue, PhD. Association of Factors With Elevated Amyloid Burden in Clinically Normal Older Individuals. JAMA Neurol. 2020;77(6):735-745
10. Martin Prince 1, Renata Bryce, The Global Prevalence of Dementia: A Systematic Review and Metaanalysis. Alzheimers Dement 2013 Jan;9(1):63-75
11. Gabriele Cipriani . Alzheimer and His Disease: A Brief History. Neurol Sci. 2011 Apr;32(2):275-9.
12. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA, USA: 2013. p. 947
13. Trzepacz P.T., Hochstetler H. Relationship between the Montreal Cognitive Assessment and Mini-mental State Examination for assessment of mild cognitive impairment in older adults. BMC Geriatr. 2015;15:107.
14. McKhann GM, Knopman DS,. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May; 7(3):263-9.
15. Zhihong Shi1. Amyloid PET in Dementia Syndromes: A Chinese Multicenter Study. J Nucl Med May 8, 2020
16. Reisa A. Sperling,. Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May; 7(3): 280–292.
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