Lochhead Paul, Hagan Kaitlin, Joshi Amit D, Khalili Hamed, Nguyen Long H, Grodstein Francine, Chan Andrew T
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Gastroenterology. 2017 Oct;153(4):971-979.e4. doi: 10.1053/j.gastro.2017.06.061. Epub 2017 Jul 18.
BACKGROUND & AIMS: Studies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim.
We used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses' Health Study II who had completed a self-administered computerized neuropsychological test battery. Multivariable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition.
We observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9-14 years vs never users, -0.06; 95% confidence interval, -0.11 to 0.00; P = .03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory (mean score difference for H2RA users of 9-14 years vs never users, -0.20; 95% confidence interval, -0.32 to -0.08; P < .001).
In an analysis of data from the Nurses' Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.
研究报告了质子泵抑制剂(PPI)的使用与痴呆之间的关联。然而,关于长期使用PPI与认知功能的数据尚缺。因此,我们研究了PPI的使用与认知功能测试表现之间的关联。由于临床适应症有共性,我们将H2受体拮抗剂(H2RAs)的关联作为次要目的进行研究。
我们前瞻性收集了护士健康研究II中13864名参与者的用药及其他潜在风险因素的数据,这些参与者完成了一项自我管理的计算机化神经心理测试组。多变量线性回归模型用于研究用药与心理运动速度和注意力、学习和工作记忆以及整体认知的综合评分之间的关联。
我们观察到PPI使用时长与心理运动速度和注意力评分之间存在适度关联(使用PPI 9 - 14年者与从未使用者的平均评分差异为-0.06;95%置信区间为-0.11至0.00;P = 0.03)。在控制H2RA使用后,该评分差异的幅度减弱。在不经常使用PPI的个体中,H2RA使用时长与较差的认知评分相关,在学习和工作记忆方面关联最为明显(使用H2RA 9 - 14年者与从未使用者的平均评分差异为-0.20;95%置信区间为-0.32至-0.08;P < 0.001)。
在对护士健康研究II的数据进行分析时,我们未观察到PPI使用与认知功能之间有令人信服的关联。我们的数据不支持PPI使用会增加痴呆风险的观点。由于我们的主要假设与PPI使用有关,我们关于H2RAs的研究结果应谨慎解读。