Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
Curr Med Chem. 2018;25(18):2166-2174. doi: 10.2174/0929867325666180129101049.
Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80 years or older. In this population, Alzheimer's disease (AD) is a common neurological disorder and type of dementia, occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated to have dementia worldwide, and it is a major cause of death in the elderly. Recent clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence of dementia, including AD. Potential molecular mechanisms related to the pathophysiology of AD (e.g., modulation of amyloid protein processing) have also been reported in both in vitro and in vivo studies. Although the clinical implications of these results are inconclusive, a literature review of the current knowledge is important for future basic and clinical research. This review summarizes the possible mechanisms connecting the use of PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to highlight the influence in humans.
质子泵抑制剂（PPIs），如奥美拉唑、兰索拉唑和雷贝拉唑，用于治疗胃食管反流病和消化性溃疡病。PPIs 的使用有所增加，特别是在老年人中，一项药物流行病学研究表明，PPIs 的使用在 80 岁或以上的人群中达到峰值。在这一人群中，阿尔茨海默病（AD）是一种常见的神经退行性疾病和痴呆类型，发病率约为 10%。目前，全球估计有超过 4500 万人患有痴呆症，是老年人死亡的主要原因。最近的临床研究表明，长期使用 PPIs 可能是痴呆症（包括 AD）发病率增加的一个危险因素。在体外和体内研究中也报道了与 AD 病理生理学相关的潜在分子机制（例如，调节淀粉样蛋白处理）。尽管这些结果的临床意义尚不确定，但对当前知识的文献综述对于未来的基础和临床研究很重要。本综述总结了 PPI 使用与 AD 发生率之间可能存在的联系的机制。此外，我们还总结了临床研究的结果，以强调其对人类的影响。
