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

Tai, Shu‐Yu; Chien, Chen‐Yu; Wu, Deng‐Chyang; Lin, Kun‐Der; Ho, Bo-Lin; Chang, Yo-Chen; Chang, Yang‐Pei

doi:10.1371/journal.pone.0171006

Cited by 85 publications

(104 citation statements)

References 40 publications

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“…Using time‐varying methods, both studies examined risk of dementia over the 18 months after ascertainment of PPI use. Lastly, PPI use was associated with greater dementia risk (HR = 1.22, 95% CI = 1.05–1.42) in a cohort study using administrative data from the Taiwan National Insurance Research Database …”

Section: Discussionmentioning

confidence: 97%

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population‐Based Study

Gray

Walker

Dublin

et al. 2017

J American Geriatrics Society

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OBJECTIVES: To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk. DESIGN: Prospective population-based cohort study. SETTING: Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington. PARTICIPANTS: Individuals aged 65 and older without dementia at study entry (N = 3,484). MEASUREMENTS: Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD). RESULTS: Over a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65-1.18), 1,095 TSDDs (HR 0.99, CI 0.75-1.30) and 1,825 TSDDs (HR 1.13, CI 0.82-1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either. CONCLUSION: Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk. J Am Geriatr Soc 66:247-253, 2018.

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Section: Discussionmentioning

confidence: 97%

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population‐Based Study

Gray

Walker

Dublin

et al. 2017

J American Geriatrics Society

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“…However, this study was at risk of misclassification bias due to self‐reporting of PPI use and missing data. A retrospective cohort study of 15,726 patients in Taiwan found that PPI use increased the risk of developing dementia compared to non‐use . These authors also reported that the risk of developing dementia increased with higher doses of PPIs.…”

Section: Resultsmentioning

confidence: 98%

Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review

Haastrup

Thompson

Søndergaard

et al. 2018

Basic Clin Pharma Tox

140

124

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Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have been raised. Therefore, side effects are important to be aware of and several suggested side effects of long-term use have been studied. In this MiniReview, we sum up the evidence of side effects related to long-term PPI treatment. Suspected side effects are mainly related to increased susceptibility to infections, secondary hypergastrinaemia, impeded absorption of micronutrients or idiosyncratic reactions. Most of the potential side effects have only been evaluated in observational studies demonstrating conflicting and weak associations with a substantial risk of confounding. However, a high probability of causality seems to be established for the side effects increased risk of gastrointestinal infections and rebound acid hypersecretion following discontinuation of treatment due to secondary hypergastrinaemia. The risk of side effects should not be a reason to withhold PPIs from patients with a true indication, and worry about poorly proven side effects should not lead to unnecessary discontinuation. The most important safety issue regarding PPI therapy is to critically evaluate the indication when initiating treatment and reconsidering the indication in long-term-treated patients.

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“…Regarding the dementia risk, initially, three cohort studies (Gomm et al, ; Haenisch et al, ; Tai et al, ) and one cross‐sectional study (Herghelegiu, Prada, & Nacu, ) found a positive association between dementia risk and PPI use. However, this association was not found in more recent studies, including a case control study (Imfeld, Bodmer, Jick, & Meier, ) and a cohort study (Gray et al, ).…”

Section: Resultsmentioning

confidence: 99%

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Barus

Béné

Deguil

et al. 2019

British J Pharmacology

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Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. These drugs can be divided into drugs targeting CNS disorders (e.g., anticholinergic drugs, antiepileptics, antipsychotics, benzodiazepines, and opioids) and drugs targeting non‐CNS disorders (e.g., antidiabetics, antihypertensives, proton pump inhibitors, and statins). Furthermore, we sought to highlight the pharmacological mechanisms underlying their possible detrimental or beneficial effects on cognition. Anticholinergic and antiepileptic drugs were excluded from this review because their effects on cognition are well known. Studies investigating benzodiazepines have revealed an increased risk of dementia. Conclusions on dementia risk or cognitive impairment regarding opioids and antipsychotic drugs are difficult to draw. These different classes appear to impair cognition not by a single clear mechanism of action specific to each class but by several relatively interdependent and interconnected mechanisms (e.g., impaired neurotransmission, neuroinflammation, neuronal death, oxidative stress, or interactions with dementia‐related pathways). The dementia risk initially associated with the use of proton pump inhibitors might have been overestimated. In contrast, statins, antihypertensive medications, and antidiabetics could potentially decrease the risk of dementia and cognitive impairment by acting in ways opposite to the mechanisms cited above. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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

Cited by 85 publications

References 40 publications

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population‐Based Study

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population‐Based Study

Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

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