Can lansoprazole (proton pump inhibitor) cause dementia?

Lansoprazole and Dementia Risk

Based on the most recent and highest quality evidence, lansoprazole use is not associated with an increased risk of dementia in older adults. 1

Current Evidence on PPI Use and Dementia

Earlier Studies Suggesting a Link

• Early observational studies from 2015-2016 suggested a possible association between PPI use and increased dementia risk:
  • A German claims data analysis reported a 44% increased risk of incident dementia in elderly patients using PPIs 2
  • Another German cohort study found a 38% increased risk of any dementia and 44% increased risk of Alzheimer's disease with PPI use 3

Recent Higher-Quality Evidence

• More recent and methodologically rigorous studies have contradicted these earlier findings:
  • A 2023 prospective cohort study (ASPREE trial) with comprehensive medication assessment found no association between PPI use and incident dementia, cognitive impairment without dementia, or cognitive decline over time 1
  • This study specifically addressed limitations of previous research by using in-person medication reviews and formal cognitive assessments rather than claims-based diagnoses 1
  • A 2022 study of over 48,000 elderly patients found that chronic PPI use was actually associated with a decreased risk of dementia and cognitive decline (HR 0.77,95% CI: 0.73-0.81) 4
  • A 2018 prospective population-based study found no association between PPI exposure and dementia risk, even with high cumulative exposure equivalent to 5 years of daily use 5

PPI Pharmacology and Metabolism

• All PPIs, including lansoprazole, are metabolized by the hepatic cytochrome P-450 system, predominantly CYP2C19 6
• Lansoprazole is a weak base converted to its active form in the acidic environment of gastric parietal cells 6
• The metabolism of lansoprazole through CYP2C19 has not been linked to neurological effects that would increase dementia risk 7

Clinical Practice Recommendations

Appropriate Prescribing of PPIs

• All patients taking PPIs should have regular review of ongoing indications for use 6
• PPIs should only be prescribed when there is a clear indication, such as:
  • Barrett's esophagus
  • Clinically significant erosive esophagitis
  • Gastroprotection in high-risk NSAID users
  • Secondary prevention of gastric/duodenal ulcers 6

De-prescribing Considerations

• Patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing 6
• The decision to discontinue PPIs should be based solely on the lack of an indication for use, not because of concern for potential adverse events like dementia 6
• Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion 6

Conclusion

The current evidence does not support avoiding or discontinuing lansoprazole due to concerns about dementia risk. The most recent and methodologically sound research indicates no association between PPI use and dementia, even with long-term use 1, 4, 5. Decisions about lansoprazole therapy should be based on appropriate gastrointestinal indications rather than unfounded concerns about cognitive effects.