Taipale Heidi, Tolppanen Anna-Maija, Tiihonen Miia, Tanskanen Antti, Tiihonen Jari, Hartikainen Sirpa
Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Am J Gastroenterol. 2017 Dec;112(12):1802-1808. doi: 10.1038/ajg.2017.196. Epub 2017 Jul 11.
The objective of the study was to investigate whether proton pump inhibitor (PPI) use is associated with an increased risk of clinically verified Alzheimer's disease (AD).
A Finnish nationwide nested case-control study MEDALZ includes all community-dwelling individuals with newly diagnosed AD during 2005-2011 (N=70,718), and up to four age-, sex-, and region of residence-matched comparison individuals for each case (N=282,858). Data were extracted from Finnish nationwide health-care registers. PPI use was derived from purchases recorded in the Prescription register data since 1995 and modeled to drug use periods with PRE2DUP method. AD was the outcome measure.
PPI use was not associated with risk of AD with 3-year lag window applied between exposure and outcome (adjusted odds ratio (OR) 1.03, 95% confidence interval (CI) 1.00-1.05). Similarly, longer duration of use was not associated with risk of AD (1-3 years of use, adjusted OR 1.01 (95% CI 0.97-1.06); ≥3 years of use adjusted OR 0.99 (95% CI 0.94-1.04)). Higher dose use was not associated with an increased risk (≥1.5 defined daily doses per day, adjusted OR 1.03 (95% CI 0.92-1.14)).
In conclusion, we found no clinically meaningful association between PPI use and risk of AD. The results for longer duration of cumulative use or use with higher doses did not indicate dose-response relationship.
本研究的目的是调查使用质子泵抑制剂（PPI）是否与临床确诊的阿尔茨海默病（AD）风险增加相关。
一项芬兰全国性巢式病例对照研究MEDALZ纳入了2005年至2011年期间所有新诊断为AD的社区居住个体（N = 70,718），并为每个病例匹配多达4名年龄、性别和居住地区匹配的对照个体（N = 282,858）。数据从芬兰全国医疗保健登记处提取。PPI的使用情况源自1995年以来处方登记数据中记录的购买情况，并采用PRE2DUP方法对用药时间段进行建模。AD为结局指标。
在暴露与结局之间应用3年滞后窗时，PPI的使用与AD风险无关（调整优势比（OR）为1.03，95%置信区间（CI）为1.00 - 1.05）。同样，较长的使用持续时间与AD风险无关（使用1 - 3年，调整OR为1.01（95%CI为0.97 - 1.06）；使用≥3年，调整OR为0.99（95%CI为0.94 - 1.04））。高剂量使用与风险增加无关（每天≥1.5规定日剂量，调整OR为1.03（95%CI为0.92 - 1.14））。
总之，我们发现PPI的使用与AD风险之间不存在具有临床意义的关联。累积使用时间较长或高剂量使用的结果未表明存在剂量反应关系。
