Department of Neurology, Medical University of Vienna, Vienna, Austria.
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177, Stockholm, Sweden.
Sci Rep. 2020 Aug 7;10(1):13371. doi: 10.1038/s41598-020-70373-8.
The use of proton pump inhibitors (PPIs) has been proposed as a potential risk factor for neurodegenerative diseases, but little is known regarding its role in amyotrophic lateral sclerosis (ALS). We therefore aimed to assess the association of PPI use with the subsequent risk of ALS, and performed a register-based nationwide nested case-control study, including 2,484 ALS cases diagnosed during July 2006-December 2013 in Sweden and 10 population controls per case that were individually matched to the case by sex, age, and area of residence. Dispenses and cumulative defined daily doses (cDDDs) of PPIs were extracted from the Swedish Prescribed Drug Register. The association of PPI use with the risk of ALS was assessed using conditional logistic regression, after applying different lag windows to avoid reverse causation. ALS patients were more likely to be dispensed with PPIs before diagnosis than controls. However, previous PPI use was not associated with an increased risk of ALS (OR = 1.08, 95% CI 0.97-1.19), and there was no dose-response relationship between cDDDs of PPIs and ALS risk (p = 0.0874), after excluding dispenses during the year before ALS diagnosis. The results were similar after excluding dispenses during the 2 or 3 years before ALS diagnosis.
质子泵抑制剂（PPIs）的使用被认为是神经退行性疾病的潜在危险因素，但关于其在肌萎缩侧索硬化症（ALS）中的作用知之甚少。因此，我们旨在评估 PPI 使用与随后发生 ALS 的风险之间的关联，并进行了一项基于登记的全国性巢式病例对照研究，该研究纳入了 2006 年 7 月至 2013 年 12 月期间在瑞典诊断的 2484 例 ALS 病例和每例病例 10 名按性别、年龄和居住地匹配的人群对照。PPIs 的配药和累积定义日剂量（cDDD）从瑞典处方药物登记处提取。使用条件逻辑回归评估 PPI 使用与 ALS 风险之间的关联，应用不同的滞后窗口以避免反向因果关系。与对照组相比，ALS 患者在诊断前更有可能接受 PPI 治疗。然而，先前的 PPI 使用与 ALS 风险增加无关（OR=1.08，95%CI 0.97-1.19），并且 PPI 的 cDDD 与 ALS 风险之间没有剂量反应关系（p=0.0874），在排除 ALS 诊断前一年的配药后。在排除 ALS 诊断前 2 年或 3 年的配药后，结果仍然相似。
