Acid reflux medications such as omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid) are so familiar that many people treat them like a daily vitamin. These drugs, known as proton pump inhibitors (PPIs), are widely used around the world to control chronic heartburn and gastroesophageal reflux disease (GERD). At the same time, a growing body of research is asking a tough question that gives many long-term users pause: could very prolonged PPI use be linked to a higher risk of dementia?

In the United States, an estimated 100 million PPI prescriptions are written each year, making PPIs one of the most frequently used drug classes. In England, omeprazole has become the second most dispensed drug, with more than 35 million prescriptions issued in 2022–23 according to a 2025 study in BJGP Open. These medications are clearly not niche. They are part of daily life for tens of millions of people, which is exactly why researchers have been examining their long-term safety in such detail.

For years, scientific studies investigating a link between PPIs and dementia produced mixed, sometimes confusing results. Many early studies grouped all PPI users together without distinguishing between short-term treatment and long-term, near-continuous use. To clarify that picture, a team of researchers from the University of Minnesota turned to data from the Atherosclerosis Risk in Communities (ARIC) study, one of the longest-running health cohorts in the United States, and asked a more precise question: does the total length of time someone takes PPIs matter for dementia risk?

Their 2023 study, published in the journal Neurology, followed participants for decades and tracked medication use through clinic visits and annual interviews. That approach allowed the team to estimate each person’s cumulative exposure instead of simply noting whether they had ever taken a PPI. Of the 497 people who had used PPIs for more than 4.4 cumulative years, 58 went on to develop dementia. After adjusting for age, blood pressure, diabetes, and other health factors, this pattern translated into a 33% higher risk of dementia compared with those who had never used PPIs. The adjusted hazard ratio in this group was 1.33, with a confidence interval of 1.0 to 1.8, which signals both a potentially important association and some uncertainty around the exact size of the risk.

Importantly, people with shorter durations of PPI use did not show an increased dementia risk in this study. The elevated risk appeared only in those with more than 4.4 years of cumulative exposure. The authors emphasized that their work was observational, meaning it can identify an association but cannot prove that PPIs cause dementia. They called for more research to confirm the finding and to better understand how, biologically, such a connection might occur if it is real.

To understand why this question matters so much, it helps to remember why PPIs are prescribed in the first place. GERD, or GORD as it is often spelled in the UK, affects roughly 10 to 20% of people and involves frequent backflow of stomach acid into the esophagus. Over time, this acid exposure can inflame and damage the esophageal lining, a condition known as esophagitis. In the most severe cases, chronic acid damage raises the risk of esophageal cancer. PPIs reduce acid production at its source by blocking an enzyme called H+/K+ ATPase in the stomach’s parietal cells. For people with significant GERD that does not respond to other measures, long-term PPI therapy can prevent serious complications and reduce daily pain.

Clinical guidelines generally recommend that PPIs be used for a four to eight week course for many common acid-related issues, then tapered or discontinued if possible. Real-world practice often looks different. A 2023 systematic review that included 28 million PPI users in 23 countries found that nearly one-quarter of adults used a PPI, most of them under age 65. Among all users, 25% had been taking PPIs for more than a year, and more than a quarter of that subgroup had been on them for over three years. In other words, long-term daily use is common.

Researchers exploring the possible connection between PPIs and dementia have proposed several biological pathways that might link the two. One idea centers on amyloid, the protein that accumulates in the brain in Alzheimer’s disease. Some laboratory work suggests PPIs may interfere with systems that help clear amyloid, which in theory could allow more of it to build up. A 2025 review in Brain Research described accumulating evidence that lengthy PPI use may have neurological effects, potentially including cognitive changes connected to disrupted molecular processes in the brain, although these findings are not yet confirmed in human populations.

A second possible pathway involves vitamin B12. Stomach acid is essential for absorbing B12 from food, and because PPIs lower acid production, long-term use can reduce B12 absorption. B12 deficiency, particularly in older adults, has been linked to cognitive decline and nerve damage. While short-term PPI use appears safe for most people, studies have associated chronic use with higher rates of B12 deficiency, a concern in individuals who are already at increased baseline risk for both cognitive impairment and nutritional shortfalls.

A third mechanism focuses on the gut microbiome. The community of bacteria that live in the digestive tract communicates with the brain through what is known as the gut-brain axis. A 2024 systematic review in BJPsych Open reported that people with dementia often have lower microbial diversity and measurable shifts in specific bacterial groups, including changes in the balance between bacteria that promote inflammation and those that reduce it. PPIs are known to alter gut bacterial composition. Some scientists suspect that this disruption might influence brain health in ways that contribute to dementia risk, a possibility explored further in work such as The Gut-Brain Connection: What Science Now Knows.

Dementia is not the only topic of concern when it comes to very long-term PPI therapy. Research has associated sustained use with higher risks of fractures, cardiovascular disease, chronic kidney disease, certain infections, and vitamin and mineral deficiencies. A 2022 population-based cohort study in BMC Medicine, using data from over 500,000 UK Biobank participants, found that PPI users had a 20% higher risk of all-cause dementia, a 23% higher risk of Alzheimer’s disease, and a 32% higher risk of vascular dementia compared to non-users. In that same study, the association between PPI use and dementia was stronger in people carrying the APOE ε4 gene variant, a well-known genetic risk factor for Alzheimer’s. Among APOE ε4 heterozygotes, the fully adjusted hazard ratio reached 1.46, and in participants aged 65 and older it was 1.68.

At the same time, other high-quality research paints a more reassuring picture. A 2026 meta-analysis in Brain Sciences reported that, when data from multiple studies were pooled, there was no statistically significant association between overall PPI use and dementia risk. A 2024 Mendelian randomization study in Scientific Reports, which used genetic tools to help minimize confounding, found no robust evidence that PPI use causes dementia and concluded it would not be appropriate to restrict medically necessary PPI prescriptions solely over cognitive concerns. Some clinicians also point out that many studies tying PPIs to dementia or other conditions were not designed to investigate PPIs specifically. Instead, they examined groups of patients who were already dealing with multiple health problems, some of whom happened to be taking acid-suppressing medication. In such situations, it can be difficult to separate the effects of the drugs from the effects of underlying illness.

This distinction between association and causation carries real-world consequences. Stopping PPIs abruptly out of fear, especially for someone with severe GERD, Barrett’s esophagus, or documented esophageal damage, could lead to significant harm, including uncontrolled pain and increased cancer risk. The emerging research does not suggest that short-term, guideline-directed PPI use meaningfully raises dementia risk. The 33% figure cited in the Neurology study applies specifically to people with more than 4.4 years of cumulative use, not to those using PPIs for a few weeks at a time to manage an acute flare.

For anyone who has been taking a PPI daily for years, the most constructive next step is a thoughtful conversation with a healthcare professional. The American Gastroenterological Association has issued formal guidance on deprescribing PPIs, stressing that the goal is not for everyone to stop, but for the right people to be on the right dose for the right duration. Over-the-counter PPIs in the United States are approved by the Food and Drug Administration for 14-day courses, used up to three times per year, which is far shorter than how many individuals actually take them. For people with milder or intermittent reflux, alternatives such as antacids, H2 blockers like famotidine, and lifestyle strategies such as maintaining a healthy weight, avoiding late meals, and limiting alcohol and trigger foods may control symptoms without long-term PPI exposure. These options are not substitutes for those with serious esophageal disease, but they can be valuable for those with less severe symptoms.

Ultimately, PPIs remain important and often life-improving medications, particularly for people with significant GERD or complications such as Barrett’s esophagus. The latest research suggests that while there may be a signal of increased dementia risk in very long-term users, the science is not settled, and causality has not been proven. Anyone concerned about their own use can work with a clinician to review the original reason for starting the medication, assess current risks and benefits, and consider whether a dose reduction, trial off therapy, or alternative strategy is appropriate. As with many areas of medicine, the best choice is personal, individualized, and grounded in a careful evaluation of both potential risks and meaningful benefits.

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