From the Guidelines
Proton pump inhibitor use is not conclusively associated with dementia or cognitive impairment, and patients should continue to use them as prescribed for approved indications. The most recent and highest quality study, an umbrella review published in the British Journal of Pharmacology in 2024 1, does not provide evidence to support a causal link between PPI use and cognitive decline. While some earlier observational studies suggested a possible association, more rigorous research has not confirmed this link.
Key Points to Consider
- PPIs, including medications such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, are effective for managing conditions like gastroesophageal reflux disease, peptic ulcer disease, and Barrett's esophagus.
- Theoretical mechanisms for potential cognitive impacts of PPIs, such as effects on vitamin B12 absorption or amyloid metabolism, remain speculative and are not supported by strong evidence.
- For patients concerned about potential risks, using PPIs at the lowest effective dose for the shortest duration necessary, and considering alternative approaches like H2 blockers or lifestyle modifications when appropriate, is a reasonable strategy.
Clinical Decision Making
When weighing the benefits and risks of PPI use, healthcare providers should consider the individual patient's needs and health status, particularly in elderly patients who may have existing cognitive concerns. The well-established benefits of PPIs for approved indications should be balanced against any potential, but unproven, risks of cognitive impairment. As noted in the umbrella review 1, tools and guidelines for assessing medication appropriateness and aiding deprescribing can be valuable resources in making informed clinical decisions.
From the Research
Proton Pump Inhibitor Use and Cognitive Impairment
- The relationship between proton pump inhibitor (PPI) use and cognitive impairment or dementia is complex and has been investigated in several studies 2, 3, 4, 5, 6.
- Some studies suggest that long-term use of PPIs may be associated with an increased risk of cognitive impairment and dementia, possibly due to mechanisms such as vitamin B12 deficiency, disruption of amyloid precursor protein processing, and neuroinflammation 2.
- However, other studies have found no significant association between PPI use and cognitive decline or dementia, and some have even reported a lower risk of cognitive impairment with PPI use 3, 6.
- A study comparing PPIs and histamine-2 receptor antagonists (H2RAs) found that H2RA use was associated with earlier progression from mild cognitive impairment to dementia and faster memory decline in Alzheimer's disease, but not with progression from normal cognition to mild cognitive impairment 5.
- The quality of evidence underlying many of the reported associations between PPIs and cognitive impairment is low, and most studies are observational, making it difficult to establish cause and effect 4, 6.
Key Findings
- PPI use has been linked to cognitive impairment and dementia in some studies, but the evidence is not consistent 2, 3, 5.
- Vitamin B12 deficiency, which can be caused by PPI use, has been linked to dementia and cognitive impairment 2.
- H2RAs may be associated with cognitive decline, specifically among people with pre-existing cognitive impairment 5.
- The quality of evidence underlying many reported associations between PPIs and cognitive impairment is low, and more research is needed to fully understand the relationship between PPI use and cognitive health 4, 6.