Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer’s Disease (AD) and non-AD related dementias. These findings were supported by preclinical studies, specifically stressing the proamyloidogenic and indirect anticholinergic effects of PPIs. However, further large-scale pharmacoepidemiological studies showed inconsistent results on the association between PPIs and dementia. Pharmacodynamically, these findings might be related to the LXR/RXR-mediated amyloid clearance effect and anti-inflammatory action of PPIs. Further aspects that influence PPI effects on AD are related to patient- specific pharmacokinetic and pharmacogenomic characteristics. In conclusion, a personalized (individualized) medicinal approach is necessary to model and predict the potential harmful or beneficial effects of PPIs in AD and non-AD-related dementias in the future.

早期的药物流行病学研究表明，质子泵抑制剂 (PPI) 可能会增加阿尔茨海默病 (AD) 和非 AD 相关痴呆的风险。这些发现得到了临床前研究的支持，特别强调了 PPI 的原淀粉样蛋白生成和间接抗胆碱能作用。然而，进一步的大规模药物流行病学研究显示 PPI 与痴呆之间的关联结果不一致。在药效学上，这些发现可能与 LXR/RXR 介导的淀粉样蛋白清除作用和 PPI 的抗炎作用有关。影响 PPI 对 AD 影响的其他方面与患者特异性药代动力学和药物基因组学特征有关。综上所述，