Association of Proton Pump Inhibitors With Risk of Dementia A Pharmacoepidemiological Claims Data Analysis
Association of Proton Pump Inhibitors With Risk of Dementia A Pharmacoepidemiological Claims Data Analysis
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DOI：
10.1001/jamaneurol.2015.4791
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发表时间：
2016-04-01
期刊：
影响因子：
29
通讯作者：
Haenisch, Britta
中科院分区：
文献类型：
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作者：
Gomm, Willy;von Holt, Klaus;Haenisch, Britta
影响老年痴呆症风险的药物可能与痴呆症预防有关。质子泵抑制剂（PPI）被广泛用于治疗胃肠道疾病，但也被证明可能参与认知能力下降。目的探讨PPI的使用与老年人痴呆症发病风险之间的关联。设计、环境和参与者我们使用2004年至2011年的观察数据进行了一项前瞻性队列研究，这些数据来自德国最大的法定健康保险公司Allgemeine Ortskrankenkassen（AOK）。每季度提供住院和门诊诊断数据（按照德国修订的《疾病和有关健康问题国际统计分类》第十次修订版编码）和药物处方数据（按照解剖学、治疗学和化学分类系统分类）。数据分析于2015年8月至11月进行。暴露处方奥美拉唑，泮托拉唑，兰索拉唑，埃索美拉唑，或雷贝拉唑。主要结局和措施的主要结局是由德国修改的国际疾病和相关健康问题统计分类，第十次修订编码的痴呆事件的诊断。使用时间依赖性考克斯回归分析PPI使用与痴呆之间的关联。该模型调整了潜在的混杂因素，包括年龄，性别，合并症，和multipharmacy.Results共73 679名参与者75岁或以上，在基线痴呆症进行了分析。接受常规PPI药物治疗的患者（n = 2950;平均[SD]年龄，83.8 [5.4]岁; 77.9%女性）与未接受PPI药物治疗的患者相比，（n = 70729;平均[SD]年龄，83.0 [5.6]岁; 73.6%为女性）（危害比，1.44 [95%CI，1.36-1.52]; P <0.001）。这一发现得到了最近对原始数据的药物流行病学分析的支持，并且与使用PPI增加小鼠脑中α-淀粉样蛋白水平的小鼠模型一致。需要进行随机、前瞻性的临床试验来更详细地研究这种联系。
IMPORTANCE Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline. OBJECTIVE To examine the association between the use of PPIs and the risk of incident dementia in the elderly.DESIGN, SETTING, AND PARTICIPANTS We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015. EXPOSURES Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.MAIN OUTCOMES AND MEASURES The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.RESULTS A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).CONCLUSIONS AND RELEVANCE The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of a -amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.