No association between proton pump inhibitor use and risk of dementia: Evidence from a meta‐analysis

Abstract

Background and AimA growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk.MethodsAn extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case–control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle–Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non‐PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software.ResultsTwelve studies (eight cohort and four case–control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96–1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case–control: P = 0.14), sex (RR 1.25 [95% CI: 0.97–1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91–1.09], P = 0.93) revealed no significant association between PPI use and dementia risk.ConclusionWe found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Proton pump inhibitors and the risk of Alzheimer’s disease and non-Alzheimer’s dementias

“…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 PPIs users 29 . However, other studies did not found this increased risk of dementia (RR 1.23; 95% CI 0.90-1.67), (RR 1.05; 95% CI 0.96-1.15) and (HR 1.10; 95 CI 0.88-1.37), respectively [28][29][30] . This risk was also not observed when we specifically assessed the risk of AD RR 1.01 (95% CI 0.78-1.32) and HR 1.06 (95% CI 0.72-1.55) respectively 27,30 .…”

Binding of omeprazole to protein targets identified by monoclonal antibodies

“…Omeprazole and other PPIs have come under increased scrutiny because they are pervasively prescribed and used, frequently at doses that are higher than required to inhibit acid secretion and for longer periods than are clinically indicated [10][11][12][13]. Furthermore, a series of investigations has linked PPI use to a number of conditions that include cardiovascular disease [14], osteoporosis [15], C. Difficile colitis [16], community acquired pneumonia [17], and dementia [18][19][20], though different groups have arrived at opposite conclusions [21,22]. The causal effect on these conditions has been debated, though a recent randomized control study suggested that only enteral infections were increased by pantoprazole administration within a three year follow-up period [23].…”

Lack of association between proton pump inhibitor use and brain aging: a cross-sectional study

“…Currently, there is no consensus on the association between the use of PPIs and the risk of dementia [5][6][7]. Inconsistencies between observational studies, especially those based on claims data, have contributed to the doubtfulness of their utility in clinical decision-making [38,39].…”

“…Inconsistencies between observational studies, especially those based on claims data, have contributed to the doubtfulness of their utility in clinical decision-making [38,39]. Specifically, summary effect estimates of several recent meta-analyses suggested no effect of PPI use on dementia risk [5,6,40,41]. On the other hand, plausible pathophysiological pathways of brain deterioration that PPIs might be involved in such as increased amyloid-β plaques, increased tau protein formation, and vitamin B12 deficiency have been described and need to be taken into account when evaluating the available evidence [4].…”

“…Although plausible pathophysiological pathways of brain deterioration that PPIs might be involved in have been described [4], previous researches have revealed conflicting evidence for a link between PPI use and the risk of dementia and cognitive decline [5][6][7].…”