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研究生:顏永杰
研究生(外文):Yung-Chieh Yen
論文名稱:阿滋海默病與ApoE4基因之相關性
論文名稱(外文):Alzheimer''s disease and Apo E epsilon4 allele
指導教授:張明永張明永引用關係龍佛衛龍佛衛引用關係
指導教授(外文):Mian-Yoon ChongFor-Way Lung
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:行為科學研究所
學門:社會及行為科學學門
學類:心理學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
論文頁數:70
中文關鍵詞:癡呆症阿滋海默病Apo E 基因型多形性狀
外文關鍵詞:dementiaAlzheimer''s diseaseApo E genotypepolymorphism
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臺灣近年來國民平均壽命逐年增長,人口的年齡結構老化,癡呆症的人口迅速增加,其衍生的相關醫療照護問題應及早研擬對策。癡呆症的診斷類別中,阿滋海默病佔最多數,造成個人、家庭及社會沉重的負擔;在眾多阿滋海默病的病因研究中,Apo E基因多形性狀的影響屢被提及,本研究的目的即在探討Apo Eε4基因與阿滋海默病在臨床表現的相關性,期能提供臨床工作者參考。
本研究採病例對照研究設計,研究組個案(50名)來自某醫學中心門診,符合NINCDS-ADRDA之「確定為阿滋海默病」(Definite Dementia of Alzheimer’s Type) 或「可能為阿滋海默病」(Probable Dementia of Alzheimer’s Type) 之標準、DSM-IV之診斷準則中阿滋海默病之標準;對照組個案(50名)則依性別、年齡收案;每一個案均接受臨床會談、基本資料蒐集、中文簡易智能狀態量表評分,並抽血進行Apo E基因型分析。
研究結果發現兩組個案均為男性22人、女性28人,平均年齡、受教育年資等無顯著差異。研究組的平均發病年齡為72.62歲,平均發病時間為3.85年。兩組個案MMSE平均得分,分別為12.08及24.56,達顯著差異(p<0.0001)。研究組50名個案中,12人有ApoEε4基因,其中1人為同質合子,其餘均為異質合子;對照組50人中,有兩人有ApoEε4基因,均為異質合子。ApoEε4基因在兩組出現的頻率分別為0.26及0.02,達顯著差異(p<0.0001)。有ApoEε4基因的人比沒有ApoEε4基因的人罹患阿滋海默病之勝算比為7.6 (95%CI:1.34~55.3;p<0.001);ApoEε4基因之出現,與罹患阿滋海默病有明顯相關性,特別是晚發型阿滋海默病、男性及低教育程度者。將Apo Eε4基因之有無作為阿滋海默病診斷依據時,其敏感度為24%,特定度為96%,陽性預測值為86%,陰性預測值為56%。
ApoEε4基因在阿滋海默病的臨床診斷、治療藥物研發及遺傳諮詢等,可作為參考,也建議進行更大規模的研究,並將ApoEε2基因、家族癡呆症病史對阿滋海默病的影響納入考慮。
The life expectancy in Taiwan grows rapidly these years. The aged society has to face the problems of increasing prevalence and burdens of dementia, especially Alzheimer’s disease. Several researchers pointed out the close relation between Apolipoprotein E polymorphism and Alzheimer’s disease. The object of this paper is to address the clinical implication of Apo Eε4.
This research is case-control designed. We recruit 50 patients of Alzheimer’s disease from the out-patient department of a medical center in Taiwan. These patients meet the criteria of “definite dementia of Alzheimer’s type” and “probable dementia of Alzheimer’s types” of NINCDS-ADRDA and the criteria of “dementia of Alzheimer’s type” of DSM-IV. Another 50 persons were recruited as control group with sex- and age-matched. Each individual received the clinical interview. Basic data, MMSE scores, and blood samples for Apo E genotyping were collected then.
There are 28 females and 22 males in the case and control groups. Yet no significant difference of average age and educational levels are found between the two groups. The mean age of onset of Alzheimer’s disease is 72.62 y/o. The average interval between onset and research is 3.85 years. The mean MMSE scores differ significantly in these two groups (respectively 12.08, 24.56, p<0.0001). The Apo Eε4 allele frequencies is much more common in the case group (0.26) than control group (0.02, p<0.0001). Among the 50 cases, 12 were Apo Eε4-positive compared with 2 of the 50 controls. There was only one homozygote for Apo Eε4 in the case group but none among the controls. The odds ratio estimate was 7.6 (p < 0.001), suggesting that the presence of Apo Eε4 is significantly correlated with Alzheimer’s disease, especially in the late-onset Alzheimer’s disease, males, and those who received less education.
The clinical diagnosis, pharmaceutical studies, and genetic counseling of Alzheimer’s disease might benefit from the Apo E polymorphism. Further researches of Alzheimer’s disease with larger size of samples is suggested.
第壹章 緒論 1
第一節 全球人口高齡化之現象 1
第二節 臺灣地區未來人口老化之趨勢 1
第三節 社會轉型中的老年人口問題 2
第四節 癡呆症之盛行率及趨勢 2
第五節 癡呆症對個人及社會之影響 3
第六節 臺灣阿滋海默病相關研究之現況 4
第七節 研究目的 6
第八節 研究假設 6
第貳章 文獻回顧與理論概念 7
第一節 阿滋海默病之歷史及臨床表現 7
第二節 阿滋海默病之病理學發現 8
第三節 阿滋海默病之治療策略 8
第四節 阿滋海默病之病因學發現 9
第五節 阿滋海默病之遺傳學研究 10
第六節 Apolipoprotein E之作用機轉與多形性狀 13
第七節 Apolipoprotein E與阿滋海默病之關聯 15
第參章 研究方法與材料 17
第一節 研究對象 17
第二節 研究方法 18
第三節 統計分析 20
第肆章 研究成果 22
第一節 研究對象基本資料 22
第二節 中文簡易智能狀態量表得分情形 22
第三節 Apo E基因型分布 23
第四節 Apo E基因型與性別之關連 23
第五節 Apo E基因型與教育程度之關連 24
第六節 Apo E基因型與發病年齡之關連 25
第七節 有家族史之阿滋海默病患者 25
第八節 Apo E基因之阿滋海默病診斷準確度 26
第伍章 討論 27
第一節 臨床診斷工具 27
第二節 中文簡易智能狀態量表得分情形 27
第三節 Apo Eε4基因型之分布 28
第四節 性別與Apo Eε4基因之關連 28
第五節 教育程度與Apo Eε4基因之關連 29
第六節 阿滋海默病發病年齡與Apo Eε4基因之關連 30
第七節 Apo Eε4基因的臨床應用 30
第八節 本研究之限制 31
第陸章 結論與建議 32
第一節 結論 32
第二節 建議 32
參考文獻 34
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