Long-Term PPI Use and Dementia Risk: What the Research Shows

Some studies associate prolonged use of proton pump inhibitors with increased dementia risk. The evidence is mixed, but it provides a good reason to review whether you still need the medication, not a reason to stop taking it on your own.

Proton pump inhibitors, commonly called PPIs, are among the most frequently used medications for reducing stomach acid.

Some are available over the counter. Others are prescribed for conditions such as gastroesophageal reflux disease, ulcers, severe inflammation of the esophagus, and protection from gastrointestinal bleeding.

Common PPIs include:

• Omeprazole (Prilosec)

• Esomeprazole (Nexium)

• Lansoprazole (Prevacid)

• Pantoprazole (Protonix)

• Rabeprazole (Aciphex)

• Dexlansoprazole (Dexilant)

These medications can provide important benefits. However, concerns have been raised about whether using them for many years may be associated with an increased risk of dementia.

The research does not give us a simple yes-or-no answer. It does give us a reason to pay attention to how long these medications are used and whether they are still medically necessary.

What Has Research Found?

A 2023 study published in Neurology followed more than 5,700 adults who did not have dementia when the study began.

People with more than 4.4 cumulative years of PPI use had a 33 percent higher rate of developing dementia during follow-up compared with people who had not used PPIs. Shorter periods of use were not associated with increased risk.

A large Danish study examined health information from nearly two million people. PPI use was associated with higher rates of dementia diagnosed before age 90. The association was stronger among people diagnosed at younger ages and increased with longer exposure.

These studies raise legitimate concerns about prolonged PPI use. They do not, however, prove that PPIs caused dementia.

Why Association Is Not Proof

The strongest evidence connecting PPIs with dementia comes from observational studies.

Researchers can adjust for many differences between PPI users and nonusers, but they cannot eliminate every possible explanation. People who require long-term PPIs may differ from nonusers in their medical conditions, medication use, lifestyle, or overall health.

This helps explain why research findings have not been consistent.

A 2023 systematic review and meta-analysis found no clear evidence that PPI use increased dementia risk overall, although some analyses suggested a possible association. The researchers concluded that the evidence could not rule out a small increase in risk.

Other studies have also found no association between PPI use and dementia or cognitive decline.

The most accurate conclusion is that long-term PPI use has been associated with dementia in several large studies, but the evidence has not established that PPIs directly cause dementia.

That may not fit neatly on a medicine bottle, but it is an important distinction.

PPIs Can Be Medically Necessary

An uncertain long-term risk must be considered alongside the known benefits of treatment.

PPIs may be needed to treat or prevent serious gastrointestinal problems, including:

• Severe erosive esophagitis

• Esophageal ulcers or strictures

• Barrett’s esophagus

• A history of gastrointestinal bleeding

• Ulcer prevention in people taking certain medications

• Other acid-related conditions requiring ongoing treatment

Stopping a necessary PPI can allow symptoms or tissue damage to return. It may also increase the risk of bleeding in some people.

The goal is not to avoid PPIs at all costs. It is to use them for a clear reason, at an appropriate dose, and for an appropriate length of time.

Review, Do Not Remove

The American Gastroenterological Association recommends that everyone taking a PPI have the medication’s ongoing indication reviewed regularly.

People without a clear reason for continued use may be considered for a supervised trial of deprescribing. Some people taking a PPI twice daily may be able to step down to once-daily dosing.

Other people should generally continue treatment because the benefits outweigh the possible risks.

Deprescribing decisions should be based on whether the medication is still indicated, not solely on fear of a possible association with dementia.

Do Not Stop Suddenly on Your Own

Stopping a PPI abruptly can cause rebound acid production. Symptoms such as heartburn or indigestion may temporarily become worse, even when the original condition has improved.

If a healthcare professional determines that the medication is no longer needed, they can recommend an appropriate plan. That plan may involve reducing the dose, changing how often it is taken, or using another strategy to manage symptoms.

Lifestyle changes may also help some people manage reflux symptoms. Depending on individual needs, these might include adjusting meal timing, avoiding personal food triggers, addressing tobacco use, or discussing weight management with a healthcare professional.

These strategies complement medical care. They do not replace treatment when a PPI remains necessary.

One Simple Action

Look at your prescription and over-the-counter medication list.

If you have been taking a PPI regularly, ask your physician or pharmacist:

What is the current reason I take this medication, and are the dose and duration still appropriate for me?

Do not stop or reduce the medication without professional guidance.

A thoughtful medication review will not provide certainty about dementia, but it can help reduce unnecessary medication exposure while preserving treatment that protects your health.

References

1. Northuis CA, Norby FL, Lutsey PL, et al. Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology. 2023;101(16):e1771–e1778.

2. Pourhadi N, Janbek J, Jensen-Dahm C, et al. Proton Pump Inhibitors and Dementia: A Nationwide Population-Based Study. Alzheimer’s & Dementia. 2024;20(2):837–845.

3. Ahn N, Nolde M, Krause E, et al. Do Proton Pump Inhibitors Increase the Risk of Dementia? A Systematic Review, Meta-Analysis and Bias Analysis. British Journal of Clinical Pharmacology. 2023;89(2):602–616.

4. Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022;162(4):1334–1342.

This article is for educational and informational purposes. It does not replace individualized medical evaluation, diagnosis, or treatment. Do not stop or change a medication without consulting a qualified healthcare professional. See the complete Disclaimer.