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Heartburn Drugs like PPIs Are Linked to Dementia

Should the FDA reconsider allowing PPIs to be sold OTC? There's growing evidence that PPIs are linked to dementia. A Swedish study shows how.

PPIs (proton pump inhibitors) are incredibly popular. Drugs like esomeprazole (Nexium), lansoprazole (Prevacid) and omeprazole (Prilosec) used to be only available by prescription. Physicians loved these acid suppressors and prescribed them in huge quantities to help cure ulcers as well as to ease symptoms of indigestion. Now some popular PPIs are available over the counter. But growing research suggests PPIs are linked to dementia. Swedish researchers may have come up with a mechanism to explain why (Alzheimer’s & Dementia, May 8, 2020).

This Reader Noticed Cognitive Decline:

Q. My husband is 75. He has been taking prescription acid-suppressing drugs for many years. I have noticed a decline in many of his cognitive abilities.

At his last physical, I brought this up to his doctor. I suspected perhaps one of his meds was causing problems, but I didn’t realize it might be the omeprazole. To be honest, when I ask his doctors about drug side effects, they think I am crazy and an annoying wife.

A. Doctors want to help their patients, not hurt them. Consequently, if someone reports drug side effects, that might be unwelcome news, but people need to stand up for their loved ones.

Physicians frequently prescribe proton pump inhibitors (PPIs) to control acid reflux. What’s more, millions now take powerful medications like esomeprazole, lansoprazole or omeprazole without a prescription to ease their heartburn symptoms.

Over the last decade, there have been several studies linking long-term use of PPIs to an increased risk of dementia (Alzheimer’s & Dementia, May 8, 2020). A new report from South Korea has been posted as a preprint online (Research Square, March 11, 2022). The investigators analyzed health insurance data from 17,225 people with Alzheimer’s disease and 68,900 age-matched controls. Older people who were taking a PPI were 36 percent more likely to be diagnosed with Alzheimer’s disease.

Another Reader Worries That PPIs Are Linked to Dementia:

Q. When I had bad reflux, I went on Nexium. After a year or so, I started noticing my memory decreasing. No way did I connect my memory problem with Nexium.

Then I was diagnosed with diabetes and realized I had to lose weight. After I lost 20 pounds, my reflux went away!

As a result, I slowly and cautiously began decreasing my Nexium. I finally stopped it about a year ago. I’ve recently noticed an improvement in my memory. I still can’t remember people’s names well, but I easily remember recent events.

A. People don’t always realize that weight loss can reduce symptoms of acid reflux (Annals of the New York Academy of Sciences, Sep. 17, 2020).  Congratulations on your success in dropping the weight and discontinuing the medication, since neither is easy to do.

Scientists have discovered that long term use of proton pump inhibitors such as esomeprazole (Nexium) or lansoprazole (Prevacid) can increase the risk of developing type 2 diabetes (Gut, online Sept. 2, 2020). The investigators recommend that doctors “exercise caution” when prescribing such drugs over the long term.

PPIs and the Brain: An Old Story

An article in the Journal of Clinical Pharmacy and Therapeutics (April, 2010) was titled:

“Proton Pump Inhibitors: Predisposers to Alzheimer Disease?”

The authors explain a mechanism whereby PPIs might affect brain function.

They concluded their article:

“Chronic consumption of PPIs may thus be a risk factor for AD [Alzheimer’s disease].”

Over the decade since that study was published, numerous other articles have suggested a link between  PPI use and dementia.

For example, a German study published in JAMA Neurology (April, 2016) was titled:

“Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis”

The investigators examined data on 73,679 people 75 years of age or older. They had no evidence of dementia at the beginning of the study. Those taking PPIs were at “significantly increased risk of incident dementia compared with patients not receiving PPI medication.”

The authors concluded:

“The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice.”

Swedish Researchers Report PPIs Are Linked to Dementia:

Fast forward to 2020. Swedish investigators have uncovered a disturbing property of proton pump inhibitors such as lansoprazole, omeprazole, rabeprazole and esomeprazole. These acid-suppressing drugs sold under the brand names Prevacid, Prilosec, Aciphex, and Nexium are potent inhibitors of an enzyme crucial for the synthesis of acetylcholine (ACh).

A Potential Mechanism:

This compound is an essential neurotransmitter that brain cells use in communication. Nerves in the digestive tract also rely on acetylcholine. When this neurotransmitter is impeded by anticholinergic drugs, there appears to be a greater risk of dementia. We have written extensively about the negative effect of anticholinergic drugs on the brain.

Here are some links:

Anticholinergic Drugs and Dementia: The Link Gets Much Stronger!
Alzheimer disease is devastating. People assume bad genes or bad luck must cause this condition. There are increasing data linking anticholinergic drugs and dementia.


Where Can I Find A List of Anticholinergic Drugs?
People taking anticholinergic drugs over a long period of time may be at greater risk of developing dementia.

Explaining Why PPIs Are Linked to Dementia:

The Swedish investigators note that a key enzyme called choline-acetyltransferase (ChAT) is crucial for the creation of ACh. Remember, ACh is essential for normal brain function. When levels of acetylcholine drop, people have trouble thinking or remembering. It turns out that PPIs are potent inhibitors of ChAT. That means levels of ACh could drop if people take PPIs for long periods of time.

The authors report that:

“Overall, these findings together with the results of pharmacoepidemiological studies, linking exposure to PPIs with incidence of dementia, are pointing at an alarming secondary mode of action for PPIs in terms of probability of exerting a clinically relevant anti‐cholinergic burden.

“Given that the best strategy against AD [Alzheimer’s disease] is the detection and when possible elimination of the risk factors, the current findings are important and suggest that the use of PPIs should be considered a legitimate risk factor for both incidence of dementia and its further progression, in particular in the elderly and in patients already suffering from dementia.”

What to Do If PPIs Are Linked to Dementia:

The Swedish researchers recommend that such PPI medications should be prescribed for the shortest time possible, particularly for the elderly and those at risk for dementia. We agree.

We have written about other complications of PPIs:

More Bad News About PPIs and Kidney Damage
PPIs for acid reflux have been linked to infections, heart attacks, strokes, nutritional deficiencies and osteoporosis. What about PPIs and kidney damage?

And this:

Yet Another PPI Complication | Acid-Suppressing Drugs and Liver Cancer?
Millions of people take powerful acid-suppressing drugs every day. They are thought to be so safe you can take them without medical supervision. A new PPI complication may have emerged.

And finally:

Why Popular Heartburn Drugs PPIs Are Linked to Premature Deaths
Acid-suppressing drugs called proton pump inhibitors (PPIs) are go-to drugs for heartburn. Should you be concerned that PPIs are linked to premature deaths?

Final Words from The People’s Pharmacy:

NEVER stop a PPI suddenly or without medical supervision! Discontinuing proton pump inhibitors abruptly can lead to horrific rebound hyperacidity and heartburn.

You can learn more about ways to gradually wean off PPIs and discover other ways to manage heartburn or acid indigestion in our eGuide to Overcoming Digestive Disorders. You will find it in our Health eGuides section.

Some people may have to take PPIs indefinitely. That may because of a serious underlying medical condition that requires a PPI. That said, doctors need to pay attention to the Swedish research. When the anticholinergic drug burden builds, the risk of dementia or Alzheimer’s disease becomes worrisome.

Please share your thoughts about PPIs in the comment section below. If you found this report of value, please share it with friends, family and other interested parties. You can do so easily by scrolling to the top of this page and clicking on icons like email, Twitter or Facebook. Thank you for helping us spread the word.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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