No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer’s Disease

Taipale, Heidi; Tolppanen, Anna‐Maija; Tiihonen, Miia; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa

doi:10.1038/ajg.2017.196

Cited by 72 publications

(86 citation statements)

References 15 publications

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“…26 Data from the Finnish nationwide health care registry also reported that among 70,718 newly diagnosed cases of Alzheimer disease, PPI use was not associated with increased risk. 27 Accumulation of amyloid-b peptides is involved in the pathogenesis of Alzheimer disease, and studies have found that lansoprazole led to higher levels of amyloid-b levels in the brains of mice. 28 The PPIs increase amyloid synthesis and decrease amyloid degradation in the brain.…”

Section: Acute and Chronic Kidney Diseasementioning

confidence: 99%

Proton Pump Inhibitors: Review of Emerging Concerns

Nehra

Alexander

Loftus

et al. 2018

Mayo Clinic Proceedings

193

129

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First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.

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Section: Acute and Chronic Kidney Diseasementioning

confidence: 99%

Proton Pump Inhibitors: Review of Emerging Concerns

Nehra

Alexander

Loftus

et al. 2018

Mayo Clinic Proceedings

193

129

View full text Add to dashboard Cite

show abstract

“…7 To date, the results of epidemiologic studies have also been inconclusive, with more recent studies pointing toward a null association between PPI use and dementia. 8,9 Current knowledge on the relationship between long-term PPI use and cognitive function, a predictor of the risk of dementia in later life, 10 is scant. 11 To investigate the association of long-term PPI use on changes in cognitive function over time, we used prospectively collected data from 2 large cohort studies conducted in Denmark where cognition was repeatedly assessed by trained interviewers, and information on PPI use was ascertained through a nationwide prescription register.…”

mentioning

confidence: 99%

Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

Wod

Hallas

Andersen

et al. 2018

Clinical Gastroenterology and Hepatology

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“…Even though the study adjusted for these variables between PPI users and non‐users, additional unrecognized baseline differences (eg, dose and duration of PPI, misdiagnosis of dementia vs delirium, OTC medications or herbal products, family history and genetics) could be present, which might explain the differences in rates of dementia rather than PPI exposure. A Finnish study by Taipale et al compared 70,718 cases of newly diagnosed AD, with up to 4 controls matched for age, sex, and region of residence. With a 3‐year lag window between exposure and outcome, PPI use was not associated with risk of AD (adjusted odds ratio [OR] 1.03; 95% CI, 1.00–1.05).…”

Section: Adverse Effects Of Proton Pump Inhibitorsmentioning

confidence: 99%

Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome

2018

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In recent years, proton pump inhibitors (PPIs) have been criticized for their various adverse interactions and side effects, creating a dilemma among practitioners regarding their use. Our goal is to review the proper use and possible side effects that might be caused by or associated with PPI use. Conclusions were drawn based on the evidence supporting or refuting short-term and long-term adverse events associated with PPI use. We also looked for the evidence regarding effects of PPIs on gut microbiota and their overall safety profile. Although there are significant discrepancies in the current literature regarding various adverse effects associated with PPI use, current data suggest that PPI use is not associated with an increased risk of bone fractures, community-acquired pneumonia, cardiovascular events, hypocalcemia, and gastric malignancies. A mild increased risk of vitamin B deficiency and chronic kidney disease, and a moderate increase in the risk of rebound hypersecretion, small intestinal bacterial overgrowth, and enteric infections, including Clostridium difficile, has been noted with PPI therapy. PPI's link with dementia and spontaneous bacterial peritonitis is not clear and requires further investigation. When used appropriately, PPIs are safe medications and are associated with minimal side effects. A clear indication and potential short-term and long-term side effects should be considered before starting PPI therapy.

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No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer’s Disease

Abstract: In conclusion, we found no clinically meaningful association between PPI use and risk of AD. The results for longer duration of cumulative use or use with higher doses did not indicate dose-response relationship.

Cited by 72 publications

References 15 publications

Proton Pump Inhibitors: Review of Emerging Concerns

Proton Pump Inhibitors: Review of Emerging Concerns

Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome

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