Dementia Risk Increases by 33 Per Cent in Millions Who Take Drug

If you’ve ever reached for a Prilosec before a spicy meal or kept a bottle of Nexium in the medicine cabinet, you’re far from alone. Acid reflux affects millions of people, and for many, proton pump inhibitors (PPIs) have become a daily habit, a simple solution to persistent heartburn and indigestion. They’re so common that most users rarely think twice about taking them. However, some researchers have begun to ask whether years of regular use could pose risks beyond the digestive system.

In the United States alone, an estimated 100 million PPI prescriptions are filled each year, making them one of the top-selling drug classes in the country. In the UK, the numbers are similarly striking, with omeprazole becoming the second most dispensed drug in England. According to a 2025 study in BJGP Open, more than 35 million omeprazole prescriptions were issued in England during 2022-23 alone. These are not niche medications. For millions of people, they’re as routine as a morning vitamin.

That widespread use is precisely why researchers have spent years investigating a possible link between long-term PPI use and dementia. Earlier studies produced conflicting results, and many failed to distinguish between occasional users and people who took the drugs for years. To address that gap, researchers turned to one of the largest and longest-running health datasets in the United States, asking a simple question: does the length of time someone takes PPIs matter?

What the Study Actually Found

Of the 497 participants who had taken proton pump inhibitors (PPIs) for more than 4.4 cumulative years, 58 developed dementia. After adjusting for age, blood pressure, diabetes, and other factors, this translated to a 33% higher risk compared with people who had never used the drugs.

PPIs include widely used medications such as omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid), which are sold over the counter and prescribed at scale around the world.

The findings come from a 2023 study in Neurology led by researchers at the University of Minnesota, using data from the long-running Atherosclerosis Risk in Communities (ARIC) cohort. Participants were followed for decades, with medication use tracked through clinic visits and annual phone interviews, allowing researchers to estimate total cumulative exposure rather than simply whether someone had ever taken a PPI.

That distinction proved important. No increased dementia risk was seen in people with shorter durations of use. The elevated risk only appeared among those with more than 4.4 years of cumulative exposure. The adjusted hazard ratio in that group was 1.33, though the confidence interval (1.0–1.8) suggests the estimate carries uncertainty.

Importantly, the authors stress that this was an observational study. It can show an association between long-term PPI use and dementia risk, but it cannot establish that the drugs cause dementia. Researchers noted that further studies are needed to confirm the finding and explore possible biological mechanisms.

Why Doctors Prescribe PPIs in the First Place

An estimated 20% of people in the United States have gastroesophageal reflux disease (GERD), a severe form of acid reflux in which stomach acid leaks back into the esophagus frequently enough to damage it over time. In the UK, the prevalence of GORD (the British spelling) is approximately 10 – 20% of the population.

People with GERD may rely on a PPI, which lowers stomach acid production. Common ones include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium). Left untreated, GERD can develop into esophagitis – chronic inflammation of and damage to the esophagus from stomach acid. In more severe cases, recurring acid damage may progress to esophageal cancer. That risk is real, and it’s the primary reason doctors prescribe these drugs long-term for patients who don’t respond to shorter courses.

PPIs reduce acid production by blocking an enzyme called H+/K+ ATPase, which is found in the parietal cells of the stomach wall and controls how much acid is secreted. For most acid-related conditions, guidelines recommend that PPIs should be discontinued four to eight weeks after starting them. Despite this, PPIs are often prescribed long-term in cases that don’t meet the guidelines for extended use.

A 2023 systematic review of 28 million PPI users across 23 countries found that nearly one-quarter of adults use a PPI, and 63% of those users are under age 65. Of all PPI users reviewed, 25% had been taking them for more than a year, and 28% of that group had continued for more than three years.

The Brain Connection: Three Possible Mechanisms

Researchers have proposed several biological pathways that could explain why very long-term PPI use might raise dementia risk, though none has been confirmed in humans.

The most discussed involves amyloid – the protein whose accumulation in the brain is a hallmark of Alzheimer’s disease. One proposed explanation is that PPIs may decrease the level of the body’s chemical responsible for clearing amyloid from the brain, theoretically increasing amyloid accumulation and raising Alzheimer’s risk. This potential link has drawn growing attention: a 2025 review published in Brain Research described how mounting evidence suggests long-term PPI use may have neurological effects, including cognitive impairment, linked to molecular disruptions in the brain.

A second pathway runs through vitamin B12. PPIs suppress stomach acid, which is needed to absorb vitamin B12 from food. Reduced B12 absorption is particularly concerning in older adults, because B12 deficiency is linked to cognitive decline and neurological damage. While PPIs are safe in the short term, emerging evidence shows risks associated with long-term use, including B12 deficiency – especially in elderly patients who are already at higher baseline risk for both deficiency and cognitive decline.

A third mechanism involves the gut microbiome – the trillions of bacteria living in the digestive tract that have a direct communication channel with the brain via the gut-brain axis. Research summarized in a 2024 systematic review in BJPsych Open found that individuals with dementia have lower microbial diversity than healthy controls, along with measurable changes in specific bacterial groups and the balance between pro-inflammatory and anti-inflammatory bacteria. PPIs are known to alter gut bacteria composition, and some researchers believe this microbiome disruption could be one route through which long-term use affects cognition. This potential connection between gut health, medication use, and brain function is explored further in The Gut-Brain Connection: What Science Now Knows.

A Growing List of Long-Term Risks

Dementia isn’t the only concern attached to prolonged PPI use. Research has associated these medications with an increased risk of fracture, cardiovascular disease, chronic kidney disease, vitamin and mineral deficiencies, and infection.

A 2022 population-based cohort study in BMC Medicine, drawing on data from over 500,000 UK Biobank participants, found that PPI users had a 20% higher risk of incident all-cause dementia compared to non-users, with a 23% higher risk of Alzheimer’s disease and a 32% higher risk of vascular dementia specifically. The same research found that the association between PPI use and dementia was notably stronger in people carrying the APOE ε4 gene variant – the most well-known genetic risk factor for Alzheimer’s – with a fully adjusted hazard ratio of 1.46 in APOE ε4 heterozygotes, and 1.68 in those aged 65 and older.

On kidney and bone health, separate research has linked prolonged PPI use to an increased risk of chronic kidney disease and fractures in the general population.

The Counterargument

The research is not unanimous. A 2026 meta-analysis published in Brain Sciences found that a pooled analysis showed no statistically significant association between PPI use and overall dementia risk, adding to an ongoing debate that has persisted in the literature for nearly a decade. A 2024 Mendelian randomization study in Scientific Reports – a genetic study design that helps control for confounding – found no robust causal relationship between PPI use and increased dementia risk, concluding it would be inappropriate to restrict clinically justified PPI prescriptions purely due to potential cognitive concerns.

Some clinicians have cautioned that many studies linking PPIs to dementia and other conditions weren’t focused on PPIs at all, but rather on other health issues in patients who happened to be taking them – meaning the association may be partly coincidental rather than causal.

The distinction matters enormously. People with severe GERD who stop taking PPIs without medical guidance risk real harm: esophageal damage, chronic pain, and in long-term cases, elevated cancer risk. Each patient needs to weigh the risks and benefits of taking a PPI with their doctor, and those originally prescribed by a gastroenterologist should ideally discuss any changes with a specialist.

What to Do Now

The 33% figure applies specifically to people who have taken PPIs for more than 4.4 cumulative years – not to people completing a standard four-to-eight-week course for an acute flare. If your PPI use has been short and doctor-directed, the current evidence doesn’t suggest you’re at meaningfully elevated risk.

If you’ve been taking a PPI daily for years, the most useful step is a direct conversation with your doctor about whether you still need it. The American Gastroenterological Association published specific guidance on deprescribing PPIs, emphasizing that the right people should be taking them and that patients shouldn’t stop abruptly due to fears that may not outweigh the severity of their condition. Over-the-counter PPIs are approved by the FDA for a 14-day course, used up to three times per year – a far shorter window than many people actually use them.

For those managing milder reflux, alternatives exist. Antacids neutralize acid on demand. H2 blockers like famotidine reduce acid production without the same enzyme-blocking mechanism. Lifestyle modifications – maintaining a healthy weight, avoiding late meals, and limiting alcohol and acidic foods – can reduce symptom frequency meaningfully. None of these replaces a PPI for someone with documented esophageal damage or Barrett’s esophagus, but for mild or intermittent symptoms, they may remove the need for the longer-term use that is generating concern. Ask your doctor whether your current dose and duration are still the right fit – and whether it’s time to reassess.

Disclaimer: The author is not a licensed medical professional. The information provided is for general informational and educational purposes only and is based on research from publicly available, reputable sources. It is not intended to constitute, and should not be relied upon as, medical advice, diagnosis, or treatment. Always consult a licensed physician or other qualified healthcare provider regarding any medical condition, symptoms, or medications. Do not disregard, avoid, or delay seeking professional medical advice or treatment because of information contained herein.

AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.

Read More: The Gut-Brain Connection: What Science Now Knows