Should PPIs Be Stopped Due to Dementia Concerns?
No—the decision to discontinue PPIs should be based solely on the lack of a valid ongoing indication for use, not because of concern about dementia or other PPI-associated adverse events. 1
The Evidence on PPIs and Dementia
The concern linking PPIs to dementia comes entirely from observational studies that cannot establish causality. Critically, no randomized controlled trial has demonstrated that PPI users have an increased incidence of dementia or any other PPI-associated adverse event. 1 The most robust recent evidence actually refutes this association:
- The ASPREE trial analysis (2023) of 18,934 adults ≥65 years found no association between PPI use and incident dementia (HR 0.88,95% CI 0.72-1.08), cognitive impairment, or decline in cognitive test scores over time 2
- A Kaiser Permanente prospective study (2018) of 3,484 older adults followed for 7.5 years found no association between cumulative PPI exposure and dementia risk, even with high cumulative exposure equivalent to 5 years of daily use 3
- An umbrella review of 11 systematic reviews/meta-analyses (2025) concluded that most evidence suggests no link between PPI use and dementia, with low certainty of existing evidence making a causal relationship unlikely 4
Conflicting observational data exists (particularly from Asian populations), but these studies suffer from residual confounding, incomplete medication assessment, and claims-based diagnoses that lead to misclassification 2, 5.
The Core Principle: Indication-Based Prescribing
The 2022 AGA Clinical Practice Update provides the definitive framework: All PPI de-prescribing decisions must be driven by whether a valid indication exists, not by fear of adverse events 1. This is critical because:
- Observational associations between PPIs and various adverse outcomes (dementia, fractures, kidney disease, infections) lack plausible mechanisms and have not been confirmed in RCTs 1
- Approximately 40% of patients have attempted to discontinue PPIs due to safety concerns, with 83% doing so without physician guidance 1
- More concerning: 80% of physicians report they would discontinue PPIs even in patients at high risk for upper GI bleeding due to these unproven concerns 1
This inappropriate discontinuation can lead to serious complications including upper GI bleeding in patients with legitimate indications.
When PPIs Should NOT Be Discontinued
Before considering any PPI discontinuation, assess for these absolute contraindications to de-prescribing 1:
High-Risk GI Bleeding Patients
- History of upper GI bleeding
- Multiple antithrombotic agents (≥2 anticoagulants/antiplatelets)
- Aspirin or NSAID use PLUS any of: age >60 years, severe comorbidity, concurrent anticoagulant, oral corticosteroid
Complicated GERD
- Severe erosive esophagitis (LA grade C/D)
- History of esophageal ulcer or peptic stricture
- Barrett's esophagus
- Eosinophilic esophagitis
Other Definitive Indications
- Zollinger-Ellison syndrome or other hypersecretory states
- Idiopathic pulmonary fibrosis (PPIs may prevent progression)
When to Consider De-Prescribing
Only consider PPI discontinuation when there is no definitive ongoing indication 1:
Review the original indication - Most PPIs are prescribed by primary care providers who should regularly document ongoing indications 1
Candidates for trial discontinuation:
- Nonerosive GERD without sustained symptom response
- Completed H. pylori eradication therapy (after 8 weeks)
- Functional dyspepsia without PPI response
- Empiric treatment without confirmed diagnosis
Step-down before discontinuation: Patients on twice-daily dosing should first be reduced to once-daily before considering full discontinuation 1
How to De-Prescribe When Appropriate
Managing Rebound Acid Hypersecretion (RAHS)
Warn patients about transient upper GI symptoms that may occur due to physiologic rebound acid hypersecretion, which can persist for 2-6 months as parietal cell hyperplasia regresses 1:
- Either tapering or abrupt discontinuation is acceptable - a trial comparing both showed no significant difference (31% vs 22% remaining off PPIs at 6 months) 1
- Symptoms from RAHS do NOT mean the patient needs to immediately resume continuous PPI therapy 1
Alternative Acid-Suppression Strategies
For managing post-discontinuation symptoms 1:
- On-demand PPIs (taking only when symptomatic rather than daily)
- H2-receptor antagonists as needed
- Neutralizing antacids for breakthrough symptoms
Approximately 75% of patients who successfully discontinued PPIs used H2-receptor antagonists or antacids for symptom control 1. Severe persistent symptoms lasting >2 months suggest either a continuing indication for PPI therapy or a non-acid-mediated cause requiring further evaluation 1.
Common Pitfalls to Avoid
Don't discontinue PPIs in high-risk bleeding patients due to dementia concerns - the proven benefit of preventing life-threatening GI bleeding far outweighs theoretical risks 1
Don't assume RAHS symptoms mean PPI failure - educate patients that transient symptoms are expected and manageable with lower-potency alternatives 1
Don't forget "hidden" bleeding risk factors - carefully assess for over-the-counter aspirin, NSAIDs, or anticoagulants before de-prescribing 1
Don't use the presence of risk factors for adverse events as justification for discontinuation - vitamin B12 deficiency risk or osteoporosis does not independently warrant PPI withdrawal if a valid indication exists 1
The Bottom Line
Dementia concerns should play zero role in PPI prescribing decisions. The highest quality prospective evidence shows no causal relationship, while the proven benefits of PPIs in preventing upper GI bleeding and managing acid-related disorders are substantial and well-established. Focus exclusively on whether a valid indication exists, assess bleeding risk carefully, and only then consider de-prescribing with appropriate patient counseling about RAHS and alternative management strategies.