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

Purpose The aim of this study was to explore the relationship between proton pump inhibitors use and the risk of dementia. Methods 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 I 2 statistic were used to evaluate the heterogeneity. Publication bias was assessed by Begg’s test and Egger’s test. Results 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. Conclusions 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.