Proton pump inhibitors (PPIs), commonly used medications for acid reflux and related conditions, have been studied for potential links to dementia, but the evidence remains inconclusive and complex. Some research suggests that long-term use of PPIs may be associated with nutritional deficiencies, particularly vitamin B12 and calcium, which are important for brain health and cognitive function. These deficiencies could theoretically contribute to cognitive decline, but a direct causal relationship between PPIs and dementia has not been definitively established[1].
PPIs reduce stomach acid production, which can impair the absorption of certain nutrients like vitamin B12. Vitamin B12 deficiency is known to cause neurological symptoms and cognitive impairment if severe and prolonged. A systematic review found that elderly patients on long-term PPI therapy (six months or more) showed a 12% to 18% decline in serum vitamin B12 levels, along with reductions in calcium and changes in bone metabolism markers[1]. Since vitamin B12 deficiency is a recognized risk factor for cognitive decline, this nutritional impact of PPIs raises concerns about potential indirect effects on dementia risk.
Epidemiological studies have observed that people with dementia are more likely to have used PPIs, with some studies reporting a modestly increased risk (e.g., 1.4 to 1.5 times higher) of dementia among PPI users compared to non-users[2]. However, these associations do not prove causation. Confounding factors such as underlying health conditions, polypharmacy, or the reasons for PPI use (e.g., chronic illness) may influence these findings. Moreover, some studies have methodological limitations, and results across studies are inconsistent.
The biological plausibility of PPIs causing dementia directly is not well established. Unlike anticholinergic drugs, which interfere with acetylcholine (a neurotransmitter critical for memory and cognition) and have a clearer link to dementia risk, PPIs do not have a known direct neurotoxic mechanism[2]. Instead, concerns focus on indirect pathways such as nutrient depletion or increased risk of infections (e.g., Clostridioides difficile) that might affect overall health and brain function[4].
Given these nuances, clinical experts recommend cautious use of PPIs, especially in older adults who are at higher risk for nutrient deficiencies and cognitive decline. Monitoring nutritional status, particularly vitamin B12 levels, and considering deprescribing PPIs when appropriate can help mitigate potential risks[1]. Large-scale, well-designed clinical trials are still needed to clarify whether PPIs contribute to dementia risk and to understand the mechanisms involved.
In summary, while there is some evidence linking long-term PPI use to nutritional deficiencies that could affect cognition, and observational studies suggest an association with dementia, there is no definitive proof that PPIs cause dementia. Patients should discuss the risks and benefits of PPI therapy with their healthcare providers, especially if used long-term.
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[1] Long-Term PPI Therapy Depletes Nutrition in Older Patients, US Pharmacist
[2] Drugs Linked to Dementia: The Complete Guide, GoodRx
[4] Do Proton Pump Inhibitors (PPIs) increase the risk of dementia?, DrOracle.ai
