Research Article: Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan

Date Published: February 15, 2017

Publisher: Public Library of Science

Author(s): Shu-Yu Tai, Chen-Yu Chien, Deng-Chyang Wu, Kun-Der Lin, Bo-Lin Ho, Yu-Han Chang, Yang-Pei Chang, Gianluigi Forloni.


Concerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia.

This study aimed to examine this association in an Asian population.

Patients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan’s National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use.

We analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non—PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR [aHR] 1.22; 95% confidence interval: 1.05–1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 [1.91–3.89]), hyperlipidemia (aHR 1.81 [1.38–2.38]), ischemic heart disease (aHR 1.55 [1.12–2.14]), and hypertension (aHR 1.54 [1.21–1.95]).

An increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted.

Partial Text

Dementia is a chronic, progressive, multifactorial neurodegenerative disorder characterized by a decline in cognitive function. With the increase in the aging population, the World Health Organization estimates the proportion of dementia cases in people aged 60 years and older will reach 22% worldwide by 2050[1], with Asia estimated to account for 59% of the cases worldwide[2]. The consequent high demand for medical therapy and care needed to treat cumulative cognitive decline will have considerable socioeconomic impact. The estimated worldwide costs of treating dementia were estimated to be US$604 billion in 2010[3]. Thus, the prevention of dementia in populations at increased risk (e.g., the elderly) may help reduce the burden caused by dementia on people and healthcare systems. Therefore, it is no surprise that commonly used drugs that could potentially increase or decrease the risk of dementia in the elderly as a consequence of their long-term use have been examined in epidemiological studies.

A total of 7863 PPI initiators from January 1, 2000, to December 31, 2003, were identified (Fig 1). After propensity score matching, 7863 PPI users were matched to the 7863 non—PPI users for the final analysis. The characteristics of both groups are listed in Table 1. All covariates were comparable after matching (Table 1). Among the study participants, 707 all-cause dementia cases occurred with an average follow-up of 9.0 years. The crude incidence rate was 5.51 per 1000 person-years among PPI users and 4.54 among non—PPI users. PPI users had a slightly higher risk of developing dementia than non-PPI users after adjusting for the covariates listed in Table 1. (HR, 1.22 [95%CI, 1.05–1.42]; Table 2) Furthermore, we found a significant association between cumulative PPI use and all-cause dementia (P for trend = .013; Table 2). The findings were similar among patients of inclusion age older than 60 y/o. (Table A in S1 File) The survival curve of the PPI use and incident dementia is depicted in Fig 2. Fig 2 depicts all-cause dementia by (A) use and (B) defined daily dose (DDD) of proton pump inhibitors (PPIs).

This study based on claims data made available by Taiwan’s National Insurance Research Database (NHIRD) revealed a significant increased risk of dementia associated with the use of PPIs in an Asian population, confirming the findings of two German studies using AgeCoDe and AOK datasets[16, 21].

This population-based cohort study found Asian PPI users to be at increased risk for dementia and that cumulative PPI use was significantly associated with dementia. This finding should be further examined through randomized, prospective clinical trials.




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