Alaeddin Nersi, Koch Alexandra, Etteldorf Rika, Stingl Julia C, Breteler Monique M B, de Vries Folgerdiena M
Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Institute of Clinical Pharmacology, Faculty of Medicine, RWTH Aachen, Aachen, Germany.
Sci Rep. 2024 Dec 16;14(1):30486. doi: 10.1038/s41598-024-81011-y.
Reports linking proton pump inhibitors (PPIs) with cognition and dementia show conflicting results, with limited evidence on underlying biological mechanisms. However, existing studies did not investigate brain microstructure, which could provide valuable insights into early structural changes indicative of cognitive decline. Analyses were based on cross-sectional baseline data from the Rhineland Study (n = 7,465; mean age 55.3 ± 13.7 years, range 30-95 years, 56.5% women). Using multivariate linear regression, we investigated associations between PPI use and cognition and brain macro- and microstructural measures (fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter integrity). Analyses were stratified by short-term (< 3 years) and long-term (≥ 3 years) PPI use, with additional age stratification (< 65 years; ≥65 years) for cognitive outcomes. PPI users, especially younger individuals, showed poorer global cognition and working memory. Notably, younger long-term users had worse total memory. PPI use was not associated with brain volume or FA, but both short-term and long-term users showed higher MD in cognitive-related brain regions. Our findings indicate that prolonged PPI use, particularly in younger long-term users, is associated with poorer cognitive performance. Moreover, PPI users showed higher MD, indicating potential white matter integrity disruptions. Further research is needed to ascertain causality and underlying mechanisms behind PPI-related cognitive decline.
将质子泵抑制剂（PPI）与认知及痴呆联系起来的报告结果相互矛盾，关于潜在生物学机制的证据有限。然而，现有研究未对脑微观结构进行调查，而脑微观结构可为认知衰退早期结构变化提供有价值的见解。分析基于莱茵兰研究的横断面基线数据（n = 7465；平均年龄55.3±13.7岁，范围30 - 95岁，女性占56.5%）。我们使用多元线性回归研究了PPI使用与认知以及脑宏观和微观结构指标（用分数各向异性（FA）和平均扩散率（MD）作为白质完整性指标）之间的关联。分析按短期（<3年）和长期（≥3年）PPI使用情况分层，对认知结果按年龄进行额外分层（<65岁；≥65岁）。PPI使用者，尤其是较年轻个体，表现出较差的整体认知和工作记忆。值得注意的是，年轻的长期使用者总记忆更差。PPI使用与脑容量或FA无关，但短期和长期使用者在与认知相关的脑区均表现出较高的MD。我们的研究结果表明，长期使用PPI尤其是年轻的长期使用者与较差的认知表现相关。此外，PPI使用者表现出较高的MD，表明潜在的白质完整性破坏。需要进一步研究以确定PPI相关认知衰退背后的因果关系和潜在机制。
