Proton pump inhibitors use and dementia risk: a meta-analysis of cohort studies



The aim of this study was to explore the relationship between proton pump inhibitors use and the risk of dementia.


A comprehensive literature search was conducted in English and Chinese databases from origination to December 2018. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. Cochran’s Q test and the I2 statistic were used to evaluate the heterogeneity. Publication bias was assessed by Begg’s test and Egger’s test.


Six studies were included, which contained a total of 166,146 participants. The overall result demonstrated a significant increase in dementia risk with proton pump inhibitors use (HR = 1.29, 95% CI = 1.12–1.49). In subgroup analyses, a significant association was detected between proton pump inhibitors use and the risk of dementia in Europe (HR = 1.46, 95% CI = 1.23–1.73) and among participants aged ≥ 65 years (HR = 1.39, 95% CI = 1.17–1.65). For the factor follow-up time ≥ 5 years, the pooled HR was 1.28 (95% CI = 1.12–1.46), demonstrating a 1.28-fold increase in the risk of dementia among proton pump inhibitors users. In the case of regional impact, participants from Europe showed an overall pooled HR estimate of 1.46 (95% CI = 1.23–1.73). There was no evidence of publication bias.


The overall result of this meta-analysis supports the hypothesis that proton pump inhibitors increase the risk of dementia. Furthermore, high-quality cohort studies are needed to confirm these findings.

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Author information




Yun Zhang and Mingming Liang conceived and designed the study, with substantial contributions from Chenyu Sun, Tingting Shi, Min Min, Evelyn J. Song, Ce Cheng, and Yehuan Sun. Yun Zhang and Mingming Liang collected, analyzed, and interpreted the data and drafted the manuscript. All authors revised it critically for important intellectual content and approved the final manuscript.

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Correspondence to Yehuan Sun.

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Zhang, Y., Liang, M., Sun, C. et al. Proton pump inhibitors use and dementia risk: a meta-analysis of cohort studies. Eur J Clin Pharmacol 76, 139–147 (2020).

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  • Proton pump inhibitors
  • Dementia
  • Meta-analysis
  • Risk