台灣老年族群使用質子幫浦阻斷劑與失智症風險之相關性探討

The Association between the Exposure of Proton Pump Inhibitor and Risk of Incident Dementia in Elderly Population

蔡孟軒(Meng-Hsuan Tsai)

指導教授 ： 溫燕霞

共同指導教授 ： 楊淑瑜(Shu-Yu Yang)

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2016年)

摘要

研究背景：隨著全球人口老化，失智症人口亦迅速成長，如何降低及預防失智症所造成之影響成為全球重要課題。近年來，質子幫浦阻斷劑 （proton pump inhibitor, PPI）廣泛地用於胃酸相關疾病之治療，並有研究顯示其可能與認知功能衰退或失智症有關，但目前相關文獻仍有限，因此本研究將探討老年族群服用PPI與失智症間之相關性，並且進一步探討是否具有劑量依賴性。
方法：本研究為回溯性世代研究，利用台灣全民健康保險研究資料庫2000年百萬承保抽樣歸人檔於1996年1月1日至2010年12月31日間之資料，納入在2000年時為65歲以上之老年族群，並依是否規律服用PPI而分成服用PPI組及未服用PPI組，再將兩組以年齡、性別及共病症1:1進行配對，追蹤至失智症發生、死亡、退保或2010年12月31日止。接著以Cox迴歸分析計算風險比（hazard ratios, HR）以及95%之信賴區間（confidence interval, CI）來評估服用PPI與失智症之相關性，且同時調整可能之影響因子。並且進一步探討PPI之累積劑量與失智症風險之相關性。
結果：本研究共納入了5,872人為研究族群，經配對後服用PPI組及未服用PPI組分別為2,936位，而研究期間共有204（3.47%）個案發生失智症。在調整可能之影響因子後，服用PPI組相較於未服藥組顯著地增加了68%之失智症風險（adjusted HR: 1.680, 95%CI: 1.263-2.235; p=0.0004）。劑量依賴性分析結果顯示，雖然在最高累積天數（>2年）及最高累積劑量（>730 cDDD）未能顯著地增加失智症之風險，但仍可觀察到PPI藥物與失智症發生風險間具有劑量依賴性（p for trend=0.0167 for cumulative duration; p for trend=0.0318 for cumulative dose）。
結論：本研究發現，老年族群服用PPI藥物可能提高失智症發生之風險，並且服用PPI藥物與失智症之風險間存在劑量依賴性。

關鍵字

老年族群 ； 質子幫浦阻斷劑 ； 失智症 ； 全民健康保險資料庫

並列摘要

Background: As the global population ages, people with dementia are increasing rapidly. Therefore, how to reduce and prevent the impact of dementia becomes an important public health issue. Proton pump inhibitors (PPI) are widely used for the treatment of gastric-related diseases nowadays and may have a role in cognition decline or even dementia. However, the literature remains scarce. This study aims to examine the effect of PPI on the risk of incident dementia among the elderly population, and further to investigate the dose-dependent response between the usage of PPI and incident dementia.
Methods: A retrospective population-based cohort study was conducted by analyzing the Taiwan Longtudinal Health Insurance Database 2000 (LHID2000) between 1996/1/1 and 2010/12/31. We included people who aged 65 years or older in 2000 as study cohort. The study population was then divided into PPI user and non-PPI user. These two groups were matched on age, sex and comorbidities by the ratio of 1:1, and were all followed until the occurrence of dementia, death, withdrawal from National Health Insurance program or the end of 2010. The Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CI) for the risk of incident dementia, and would adjust for the potential risk factors. Furthermore, we would examine the dose dependent response of PPI on the risk of incident dementia.
Results: A total of 5,872 patients were identified as study population. After matching on age, sex and comorbidities, there were 2,936 individuals in each PPI user group and non-PPI user group, and 204 (3.47%) individuals develop dementia during follow-up period. After adjusting for potential risk factors, PPI user group significantly increased 68% risk of incident dementia compared to non-PPI user group (adjusted HR: 1.680, 95%CI: 1.263-2.235; p=0.0004). The dose-dependent response analysis indicated that although the highest cumulative duration group (>2 years) and the highest cumulative dose group (>730 cDDD) failed to increase the risk of incident dementia significantly, but we still observed the dose-dependent response between the use of PPI medication and the risk of incident dementia (p for trend=0.0167 for cumulative duration; p for trend=0.0318 for cumulative dose).
Conclusions: The usage of PPI medication was associated with a higher risk to develop dementia among the elderly population, and there is a dose-dependent relationship between PPI medication and risk of incident dementia.

並列關鍵字

elderly ； proton pump inhibitors ； dementia ； National Health Insurance Database

參考文獻

1. 楊惠琄. 失智症的介紹及治療. 秀傳季刊. 2009;24(3):6-7.

2. Martin Prince, Anders Wimo, Maëlenn Guerchet, et al. World Alzheimer Report 2015 The Global Impact of Dementia. 2015. Available from: https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf.

3. Sun Y, Lee HJ, Yang SC, et al. A nationwide survey of mild cognitive impairment and dementia, including very mild dementia, in Taiwan. PloS one. 2014;9(6):e100303.

4. 104年第29週內政統計通報(104年6月底人口結構分析). 內政部統計處. 2015. Available from: http://www.moi.gov.tw/files/news_file/week10429.pdf. Accessed April, 2016.

5. 中華民國2012年至2060年人口推計報告. 行政院經濟建設委員會. 2012. Available from: http://iknow.stpi.narl.org.tw/Post/Files/policy/2012/policy_12_037_2.pdf. Accessed April, 2016.