Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.
Drug Saf. 2018 Dec;41(12):1387-1396. doi: 10.1007/s40264-018-0704-9.
Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer's disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies.
The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD).
We conducted a case-control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration.
As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80-0.97) or VaD (aOR 1.18, 95% CI 1.04-1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87-1.02) or VaD (aOR 0.99, 95% CI 0.89-1.10).
In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.
观察性研究表明，质子泵抑制剂（PPIs）的长期使用与阿尔茨海默病（AD）的风险增加有关。这些研究中并未探讨暴露持续时间的作用，以及这是否适用于其他痴呆亚型。
本研究旨在研究长期使用 PPIs（或组胺 2 受体拮抗剂[H2RAs]，作为阴性对照）与发生 AD 或血管性痴呆（VaD）风险之间的关系。
我们在英国的临床实践研究数据库（CPRD）中进行了病例对照分析。我们确定了 1998 年至 2015 年间 41029 名年龄≥65 岁的新诊断为 AD 或 VaD 的患者，并按年龄、性别、日历时间、全科医生和记录病史的年数与无痴呆对照组 1:1 匹配。我们应用条件逻辑回归分析来计算发生 AD 或 VaD 的调整比值比（aOR）及其 95%置信区间（CI），按暴露持续时间对 PPI 或 H2RA 的使用进行分类。
与未使用相比，长期使用 PPI（≥100 张处方）与 AD（aOR 0.88，95%CI 0.80-0.97）或 VaD（aOR 1.18，95%CI 1.04-1.33）的发病风险增加无关。长期使用 H2RA（≥20 张处方）也与 AD（aOR 0.94，95%CI 0.87-1.02）或 VaD（aOR 0.99，95%CI 0.89-1.10）的发病风险增加无关。
在这项大型病例对照分析中，我们没有发现任何证据表明 PPI 或 H2RA 使用与 AD 或 VaD 风险增加相关。
