研究背景與目的:
失智症是腦部疾病的其中之一，此疾病會導致認知功能逐漸地退化，並使個人的日常生活受到影響。失智症的危險因子包含，高血壓、高膽固醇、糖尿病、代謝症候群、肥胖和抽菸等。
過去研究顯示，血糖波動會造成腦部神經受損，尤其在大腦皮質和海馬迴，因為血糖波動變大會增加自由基的產生，導致神經元受損和澱粉樣蛋白前驅蛋白(amyloid precursor protein)的堆積造成神經的傷害。眾所周知，所有種類之口服降血糖藥均可改善第二型糖尿病人之血糖值，其中Acarbose(α-glucosidase inhibitor)可減少碳水化合物吸收進而改善飯後高血糖並減少血糖波動與其他口服降血糖藥有所不同。因此，本研究運用分析健保資料庫之資料來探討第二型糖尿病患使用Acarbose與失智症的相關性。
研究方法:
本研究為回溯性世代研究，資料來源為台灣的全民健康保險研究資料庫，於2000年至2005年間篩選6,950位60歲以上被診斷為糖尿病人之新發個案，定義診斷日期為研究的指標日期(index date)。本研究分為兩組，一組使用 Acarbose治療，另一組沒有使用Acarbose治療，兩組均持續追蹤1年、3年、5年。以存活分析中的Kaplan-Meier Curve、Log-Rank Test以及Cox比例危險模型來分析結果。
研究結果:
總共2,907符合收案條件並納入本研究，Acarbose組969人，非Acarbose組1,938人。Acarbose組平均4.96年的觀察中，發生失智症(含老年性癡呆症、阿茲海默症、血管型失智症)事件共有17件(1.8%)，非Acarbose組平均4.95年的觀察中，發生失智症事件共有49件(2.5%)。在Acarbose組發生阿茲海默症事件共有2件(0.2%)，非Acarbose組，發生阿茲海默症事件共有5件(0.3%)。在Acarbose組發生血管型失智症事件共有16件(1.7%)，非Acarbose組，發生血管型失智症事件共有47件(2.4%)。以Kaplan-Meier方法分析看出，兩組隨著時間的進行，其存活機率遞減的速度差異不大；而log rank檢定p值為0.190，統計學上無顯著差異。在COX regression的分析，未校正其他危險因子前，Acarbose組相較於非Acarbose組的失智症(含老年性癡呆症、阿茲海默症、血管型失智症)風險比(Hazard ratio)為0.69(95%CI[0.40-1.20])，統計學上無顯著差異。經校正後，風險比(Hazard ratio)為0.67(95%CI[0.38-1.17])，仍然在統計學上無顯著差異。
研究結論:
本研究結果得知，針對第二型糖尿病患者且年齡大於60歲，使用Acarbose組與非Acarbose組，兩組發生失智症風險是相當。本研究仍有許多限制因素，未來需有更多的研究證實，第二型糖尿病患者使用Acarbose可減少發生失智症的風險。

Background:
Dementia is one of brain diseases and causes cognitive function regression gradually. Meanwhile, dementia also affects a person’s daily life. The risk factor of dementia included hypertension, hyperlipidemia, diabetes mellitus, metabolic syndrome, obesity and smoking. etc. Previous studies have shown results that glucose excursions lead to brain neuronal damage, especially in cerebral cortex and hippocampus in terms of high glucose excursions level leads to increase free radical and accumulation of amyloid precursor protein in damaged neuronal. All of oral antidiabetic (OAD) agents could improve glucose level and Acarbose, α-glucosidase inhibitor, delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. Currently, there were a few studies to discuss Acarbose in treating dementia. Our study aims to understand that the relationship of Acarbose and the risk of dementia in T2DM patients.
Method:
A retrospective cohort study and utilize Nation Health Insurance(NHI) database from 2000 to 2005 representing 1 million sampling from whole population in Taiwan. The study subjects included newly diagnosed T2DM patients within use Acarbose or other OADs, older than 60 years from 2000 to 2005 and never use OAD or diagnosed dementia before 2000. The primary outcome was dementia after the start of follow up. The results were analyzed using Cox proportional hazard regression.
Results:
Among 2,907 patients with newly diagnosed T2DM patients identified during 2000 to 2005, 969(33%) were treated with Acarbose, 1,938(67%) were treated with non-Acarbose. During 5 years(Acarbose: median 4.96 years, Non-Acarbose median 4.95 years ) of follow up, 17 patients(1.8%) who had received Acarbose treatment developed dementia as compared to 49 patients(2.5%) who never used Acarbose therapy. The crude hazard ratio(HR) and adjusted HR were 0.69(95%CI[0.40-1.20]) and 0.67(95%CI[0.38-1.17]) , respectively.
Conclusion:
In patients with T2DM aged over 60 years without preexisting dementia, the stratified analysis indicated no increased risk of dementia in Acarbose patients. (all P =0.190). Additional randomized controlled trials are warranted to confirm our results.

目錄
致謝 I
摘要 II
Abstract IV
目錄 VI
表目錄 VII
圖目錄 VIII
第一章 緒論 1
第一節 前言 1
第二節 背景分析 2
第三節 研究目的 2
第二章 文獻探討 1
第一節 失智症之病因與分類 1
第二節 糖尿病之病因與分類 2
第三節 失智症與糖尿病相關性研討之探討 4
第三章 研究方法 6
第一節 研究設計 6
第二節 研究變相及操作定義 10
第三節 資料處理流程 12
第四節 統計方法 14
第四章 研究結果 16
第一節 基本資料分析 16
第二節 存活分析 21
第五章 討論 29
第一節 基本資料 29
第二節 失智症事件與其影響因子之關係探討 36
第三節 降血糖藥物的用藥醫囑性 38
第四節 研究設計討論 39
第六章 研究限制 41
第七章 結論與建議 42
參考文獻 43

表目錄
表1 Acarbose藥品健保代碼（衛生福利部食品藥物管理署） 7
表2 國際疾病分類代碼 8
表3 主要研究變相操作定義 11
表4 疾病共變因子 12
表5 基本資料和過去疾病分布 19
表5 基本資料和過去疾病分布(續) 20
表6 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(連續5年的追蹤) 23
表7 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(連續1,3,5年的追蹤) 25
表8 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(年齡與性別) 28

圖目錄
圖1 研究流程 17
圖2 Kaplan-Meier曲線分析 Acarbose組/非Acarbose組與失智症之關聯性 22
圖3 2016年美國臨床內分泌醫師協會糖尿病指引( American Association of Clinical Endocrinologists 2016) 32
圖4 2012年 國際糖尿病聯盟糖尿病指引(IDF Diabetes Treatment Algorithm 2012) 33
圖5 2015年中華民國糖尿病照護指引 34
圖6 Acarbose作用機轉 35

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