Some observational studies and reviews report an association between proton pump inhibitors like omeprazole and an increased risk of dementia, whereas comprehensive meta-analyses find no statistically significant association or causal link.
agonist [ 75 ]. LXRs are transcription factors that modify expression of genes related to cholesterol metabolism. Hence, lansoprazole increases ATP-binding cassette transporter (Abca1) and apolipoprotein- (Apo-) E levels in primary astrocytes, both genes regulated by LXR [ 75 ]. Moreover, ApoE lipid complexes mediated by ABCA1 inhibit A β plaque aggregation, thereby supporting the theory that lansoprazole can act as a therapeutic agent in AD [ 17 ]. 5. Clinical Association between PPIs and Risk of Dementia, AD, and Cognitive Impairment
Based on a systematic review from 2017, four European observational studies have investigated association between PPI use and dementia. Three studies have found a positive association between dementia and omeprazole, esomeprazole, lansoprazole, and pantropazole, with an approximately 1.4-fold increased risk of any dementia in cohorts using PPIs (95% CI, 1.36–1.52; P < 0.001) [ 76 ]. Similarly, in a recent prospective cohort study in Asian population ( n = 15726, 7863 PPI users), an association with dementia has been found (aHR, 1.22; 95% confidence interval, 1.05–1.42) [ 15 ]. In contrast, the fourth European report included in the systematic review found a negative association (OR dementia with PPI use = 0.94 (95% CI, 0.90–0.97) P = 0.0008) [ 76 ]. Herghelegiu and colleagues [ 77 ] conducted a single-center case-control study that compared 148 PPI users (aged at least 65 years old) with a control group of nonusers during an 8-month period. They confirmed statistically significant association between PPI use and dementia. However, bias was influenced by the small study sample. Further, they did not take into account fundamental cofounders such as age, sex, history of stroke, and smoking status, which are considered risk factors for dementia. Conversely, Booker and coworkers [ 16 ] found statistically significant reduction between dementia and PPI use with a case-control study using a database of general practice medical records in
<h4>Background</h4>Proton pump inhibitors (PPIs) are an established kind of drugs used to the treatment of most acid-related diseases. Some prospective studies have noticed that PPI use was associated with increased dementia risk. However, the results of those studies were inconsistent and controversial. This meta-analysis aims to determine the association of PPI use and risk of dementia among older people.<h4>Methods</h4>Relevant articles were systematically identified by searching the PubMed, EMBASE, and Cochrane Library databases from inception to February 2018. Cohort studies that reported the risk of dementia or Alzheimer's disease (AD) among PPI users compared with non-PPI users were included. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). The publication bias was detected by a funnel plot and Egger test. The meta-analysis will abstract risk estimates including relative risks (RRs), hazard ratios (HRs), and odds ratios (ORs) with a 95% confidence interval (CI) for the associations between PPI use and dementia or Alzheimer's risk. Study-specific results were pooled using a random-effects model.<h4>Results</h4>Six cohort studies were selected finally. The pooled RRs of dementia and AD were 1.23 (95% CI: 0.90-1.67) and 1.01 (95% CI: 0.78-1.32), respectively, compared with those of non-PPI use. The Egger test and funnel plot showed no existence of publication bias. Overall, there was no statistically significant association between PPI use and risk of dementia or AD (P >.05).<h4>Conclusions</h4>This meta-analysis suggests that there was no statistical association between PPIs use and increased risk of dementia or AD.
Proton pump inhibitors (PPIs) are the most prescribed gastric acid suppressant drugs; the category includes omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. In 2015, a study suggested that PPI use was associated with an increased risk of dementia. An early meta-analysis confirmed this concern, but the findings were inconsistent in subsequent meta-analyses. Also problematic is that these meta-analyses used questionable approaches, and their findings were characterized by very high heterogeneity. Notably, the high heterogeneity appeared to be driven by large studies with widely different outcomes. Nonetheless, one finding stands out in the body of research examined: older subjects who initiated and continued PPIs (implying chronic use) were at a significantly increased risk of dementia and mild cognitive impairment. Although there are causal and non-causal pathways that associate PPI use with dementia, for reasons that are explained in this article, a cause-effect relationship cannot at present be presumed; so, PPI use is best considered to be a marker of future dementia risk. However, because chronic use of PPIs has been associated with many adverse medical outcomes (eg, disturbances of the gut microbiome, orthopedic complications), and because some PPIs are associated with pharmacokinetic drug interactions (mainly inhibition of CYP2C19), it would be wise to limit the use of PPIs to the shortest duration necessary and to deprescribe PPIs when there does not appear to be need for their continuation.
Introduction: Concerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia. Objective: This study aimed to examine this association in an Asian population. Methods: Patients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan’s National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined d
Aim: To characterize the usage profile and the factors associated with the prolonged use of proton pump inhibitor drugs in a community pharmacy. Methodology: This is a cross-sectional, prospective and observational study involving interviews with 410 patients who acquired PPI for their own use from community pharmacies. To characterize the factors associated with the prolonged use of PPI, a multivariate logistic regression model was used. Results: Pantoprazole (42.7%) and omeprazole (31%) were the most acquired PPIs, prescribed mainly by gastroenterologists (49.5%). They are used in the mornin
Organization's List of Essential Medicines, omeprazole being the specific listed example. These medications are used in the treatment of many conditions, such
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. The body eventually synthesizes new proton pumps to replace the irreversibly inhibited ones—a process driven by normal cellular turnover, which gradually restores acid production.
Proton-pump
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. The body eventually synthesizes new proton pumps to replace the irreversibly inhibited ones—a process driven by normal cellular turnover, which gradually restores acid production.
Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action, and heavy use of antacids. Potassium-competitive acid blockers (PCABs) have entered the market since the 2010s.
PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the World Health Organization's List of Essential Medicines, omeprazole being the specific listed example.
A 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. An 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. Twelve 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. We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.
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