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      Proton pump inhibitor use does not increase dementia and Alzheimer’s disease risk: An updated meta-analysis of published studies involving 642305 patients

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      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Recent studies have indicated an increased risk of dementia and Alzheimer’s disease (AD) among people who consume proton pump inhibitors (PPIs), but the results of those studies are inconsistent. This meta-analysis aimed to explore the correction risk of dementia and AD among PPI users. The literature search for relevant studies was conducted in PubMed, Web of Science, EMBase and ScienceDirect. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were used to assess the relationship between the PPIs and risk of dementia and AD. Ten independent studies that involved 642305 participants were included in this meta-analysis. PPI users were unassociated with dementia (HR = 1.04, 95% CI 0.92–1.15; I 2 = 95.6%, p < 0.001) and AD (HR = 0.96, 95% CI 0.83–1.09; I 2 = 80.7%, p <0 .001). No evidence of publication bias was detected by Begg’s and Egger’s test. Sensitivity analyses showed no important differences in the estimates of effects. The current evidence indicates that PPI use does not increase dementia and AD risk. The remarkable heterogeneity among the studies warrants a further review of our findings.

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          Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

          Yoshikazu Kinoshita, Norihisa Ishimura, Shunji Ishihara (2018)
          Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.
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            Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia

            Felicia C Goldstein, Kyle Steenland, Liping Zhao … (2017)
            Background/Objective Controversy exists over whether proton pump inhibitors (PPIs) increase risk for dementia. This study examined the risk associated with PPIs on conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer’s disease (AD). Design Observational, longitudinal study. Setting Tertiary academic Alzheimer Disease research centers funded by the National Institute on Aging. Participants Research volunteers ≥ 50 years old with 2 to 6 annual visits. Eight hundred and eighty four were taking PPIs at every visit, 1,925 took PPIs intermittently, whereas 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Analytic Plan Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition into MCI or dementia, or annual conversion of baseline MCI into dementia, controlling for demographics, vascular comorbidities, mood, and anticholinergics and histamine-2 receptor antagonists. Results Continuous (Always vs. Never) PPI use was associated with a decreased risk of decline in cognitive function (HR 0.78, 95% CI 0.66–0.93, p=.005) and decreased risk of conversion to MCI or dementia due to AD (HR 0.82, 95% CI 0.69–0.98, p=.026). Intermittent use was also associated with decreased risk of decline in cognitive function (HR 0.84, 95% CI 0.76–0.93), p=.001) and risk of conversion to MCI or dementia due to AD (HR 0.82, 95% CI 0.74–0.91), p=.001). This reduced risk was found for persons with either normal cognition or MCI. Conclusion PPIs were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and the lack of dispensing data. Prospective studies are needed to confirm these results in order to guide empirically based clinical treatment recommendations.
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              Patterns and predictors of proton pump inhibitor overuse among academic and non-academic hospitalists.

              Shaker Eid, Adel Boueiz, Suchitra Paranji … (2010)
              In the hospital setting, several studies have reported proton pump inhibitor (PPI) overuse, a majority of which is continued after discharge. In addition to being expensive, PPIs are associated with an increased risk of infections, osteoporosis and serious drug interactions. We examined the trends and predictors of PPI guidelines non-compliance among academic and non-academic hospitalists in USA.
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                Author and article information

                Contributors
                Ya Qi Song: Role: ConceptualizationRole: Writing – original draft
                Yong Li: Role: Data curationRole: Project administrationRole: Writing – review & editing
                Su Li Zhang: Role: ConceptualizationRole: Data curationRole: Project administration
                Jie Gao: Role: Data curationRole: Writing – original draft
                Shun Yi Feng:
                ORCID: http://orcid.org/0000-0002-6114-7837
                Role: ConceptualizationRole: SoftwareRole: Writing – review & editing
                Gianluigi Forloni: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 2 July 2019
                Publication date Collection: 2019
                Volume: 14
                Issue: 7
                Electronic Location Identifier: e0219213
                Affiliations
                [001]Emergency Department, Cangzhou Central Hospital, Yunhe Qu, Cangzhou, China
                Istituto Di Ricerche Farmacologiche Mario Negri, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6114-7837
                Article
                Publisher ID: PONE-D-19-01000
                DOI: 10.1371/journal.pone.0219213
                PMC ID: 6605652
                PubMed ID: 31265473
                SO-VID: 63b9df37-264d-4952-ab82-70849b440707
                Copyright © © 2019 Song et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 11 January 2019
                Date accepted : 10 June 2019
                Page count
                Figures: 4, Tables: 3, Pages: 9
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Mental Health and Psychiatry
                Subject: Dementia
                Subject: Alzheimer's Disease
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Dementia
                Subject: Alzheimer's Disease
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Neurodegenerative Diseases
                Subject: Alzheimer's Disease
                Subject: Medicine and Health Sciences
                Subject: Mental Health and Psychiatry
                Subject: Dementia
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Dementia
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Cohort Studies
                Subject: Science Policy
                Subject: Research Integrity
                Subject: Publication Ethics
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Case-Control Studies
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Structures and Organelles
                Subject: Cell Membranes
                Subject: Membrane Proteins
                Subject: Proton Pumps
                Subject: Biology and Life Sciences
                Subject: Neuroscience
                Subject: Cognitive Science
                Subject: Cognitive Neuroscience
                Subject: Cognitive Neurology
                Subject: Cognitive Impairment
                Subject: Biology and Life Sciences
                Subject: Neuroscience
                Subject: Cognitive Neuroscience
                Subject: Cognitive Neurology
                Subject: Cognitive Impairment
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Cognitive Neurology
                Subject: Cognitive Impairment
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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