Proton pump inhibitors do not increase the risk of dementia: a systematic review and meta-analysis of prospective studies
Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and demen...
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| Published in | Diseases of the esophagus Vol. 33; no. 10 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
12.10.2020
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| Online Access | Get full text |
| ISSN | 1120-8694 1442-2050 1442-2050 |
| DOI | 10.1093/dote/doaa041 |
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| Abstract | Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer’s dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5–11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86–1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66–1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70–1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up. |
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| AbstractList | Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer's dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5-11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86-1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66-1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70-1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up.Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer's dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5-11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86-1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66-1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70-1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up. Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer’s dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5–11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86–1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66–1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70–1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up. |
| Author | Desai, Madhav Kohli, Divyanshoo Mohammad, Bilal Chandrasekhar, Viveksandeep Thoguluva Fathallah, Jihan Vaezi, Michael Dasari, Chandra Sharma, Prateek Nutalapati, Venkat Katz, Philip O Srinivasan, Sachin |
| Author_xml | – sequence: 1 givenname: Madhav orcidid: 0000-0001-8871-3627 surname: Desai fullname: Desai, Madhav organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 2 givenname: Venkat surname: Nutalapati fullname: Nutalapati, Venkat organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 3 givenname: Sachin orcidid: 0000-0002-2250-5347 surname: Srinivasan fullname: Srinivasan, Sachin organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 4 givenname: Jihan surname: Fathallah fullname: Fathallah, Jihan organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 5 givenname: Chandra surname: Dasari fullname: Dasari, Chandra organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 6 givenname: Viveksandeep Thoguluva surname: Chandrasekhar fullname: Chandrasekhar, Viveksandeep Thoguluva organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 7 givenname: Bilal surname: Mohammad fullname: Mohammad, Bilal organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 8 givenname: Divyanshoo orcidid: 0000-0002-7801-0044 surname: Kohli fullname: Kohli, Divyanshoo organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 9 givenname: Michael surname: Vaezi fullname: Vaezi, Michael organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 10 givenname: Philip O surname: Katz fullname: Katz, Philip O organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA – sequence: 11 givenname: Prateek orcidid: 0000-0002-4712-0152 surname: Sharma fullname: Sharma, Prateek organization: Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA, Department of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas, USA, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA, Department of Gastroenterology, Weill Cornell Medical College, New York, New York, USA |
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