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Proton Pump Inhibitors: Do Heartburn Drugs Increase Your Risk of Dementia?

Proton Pump Inhibitors: Do Heartburn Drugs Increase Your Risk of Dementia?

Could common heartburn drugs put you at risk of dementia?

Proton pump inhibitors (PPIs), a group of drugs used for stomach acid disorders such as peptic ulcers or gastroesophageal reflux disease (GERD), are among the most widely used drugs in the world, with long-term use reported in 2–3 percent of older Americans. Unsurprisingly, alarm bells have been ringing after a recent publication in JAMA Neurology reported that the use of these drugs is associated with a 44 person increased risk of dementia. In a companion editorial, Dr. Lewis Kuller from the University of Pittsburgh estimated that, if the risk is real, these drugs are leading to 10,000 new cases of dementia just within people aged 75–84 years. Whether PPIs pose a real risk, however, remains to be seen.

The recent study used data from a German health insurance provider of people aged 75 years or older to show that patients who had used PPIs were 44 percent more likely to develop dementia. The same group reported similar results in an earlier study on a different set of elderly Germans. This consistency is marred, however, by a third study from another group of German scientists reporting that the use of PPIs is associated with a 7 percent lower risk of dementia.

All of these studies were observational, which makes it hard to draw conclusions. In the recent study, Germans who took PPIs were also more likely to have depression, cardiovascular disease, and polypharmacy (i.e., they were prescribed a lot of drugs). These conditions are all associated with a higher risk of dementia. While the scientists tried to control for these risks in their analysis, it is difficult to be sure that they succeeded without more studies to replicate their results and to look for extra clues in the data like a dose-response relationship, where higher doses of the drugs relate to a higher risk.

From a biological perspective, PPIs could either worsen or protect from the disease pathways that cause dementia. Long-term, human studies suggest that use of these drugs can increase the risk of vitamin B12 deficiency, a serious and often undiagnosed condition in the elderly that can impair brain function. Animal and cell culture studies also suggest that PPIs can increase beta-amyloid plaques, a primary component of Alzheimer’s disease, but other studies suggest that these drugs can decrease beta-amyloid. PPIs were also reported to protect against inflammation and oxidative stress in preclinical studies of dementia. Some PPIs bind so powerfully to neurofibrillary tangles, a key component of Alzheimer's disease, that the drugs are being used to create tools to visualize the tangles in people using PET imaging. Whether that binding of the drugs can alter the disease process, however, is unknown.

Why is there so much contradictory evidence? Many different biological pathways can contribute to dementia. PPIs have the potential to influence many of those pathways but far too little research has been done to learn if the drugs pose a genuine risk to patients. Except for B12 deficiency, none of these effects have been verified to occur in humans.

We need observational research in humans with enough data to look at the long-term risks and benefits associated with specific types of PPIs used at different doses and for different lengths of time in different types of patients. This data will be hard to come by. But if we want to fully understand the risks or benefits posed by these and other drugs, we need to routinely test cognitive function in healthcare.

Dr. Penny Dacks was previously the Director of Aging and Alzheimer’s Disease Prevention at the Alzheimer's Drug Discovery Foundation. She was trained in neuroscience at the Mount Sinai School of Medicine, the University of Arizona, and Queen's University (Canada) with individual fellowships from the National Institute of Health, the Evelyn F. McKnight Brain Research Foundation, the ARCS Foundation and the Hilda and Preston Davis Foundation. She has authored over 18 peer-reviewed scientific articles and is a member of the Society for Neuroscience, the Gerontological Society of America, the Endocrine Society and the Association for Women in Science.

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