Dementia: Proton pump inhibitor use linked to higher risk

Evan Walker
Evan Walker TheMediTary.Com |
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Could some medication used to treat acid reflux increase the risk of dementia? Image credit: Colin Anderson Productions pty ltd/Getty Images.
  • Dementia is a condition that influences thinking and function ability.
  • Because of the immense impact of dementia, researchers are seeking to understand factors that influence someone’s risk of developing dementia.
  • A study found that in people between the ages of 60 and 90 years, using proton pump inhibitors, a type of gastric acid-blocking medication, was associated with an increased risk for dementia.

Dementia is a common condition, but it is often unclear why some people develop dementia and others do not. Researchers are interested in studying what factors contribute to dementia risk.

A study recently published in Alzheimer’s and Dementia looked at how the use of some medication prescribed for the treatment of acid reflux, or heartburn.

They found that proton pump inhibitors may increase the risk of dementia, regardless of when the treatment is initiated.

Proton pump inhibitors include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), which are over-the-counter drugs, as well as pantoprazole (Protonix) and rabeprazole (Aciphex), which are prescription-only drugs.

Using proton pump inhibitors for a longer time frame was associated with an even higher level of risk of developing dementia, the recent study found.

Dementia is an umbrella term referring to several subtypes of neurodegenerative conditions, the most common of which is Alzheimer’s disease. People with dementia may not remember what they used to, and they may experience challenges that make it hard to live independently.

Certain risk factors can increase someone’s chances of developing dementia. These include advanced age, social isolation, high blood pressure, and depression. However, there are many dementia risk factors that experts still do not fully understand.

The researchers who conducted the current study wanted to better understand the use of proton pump inhibitors (PPIs) and their associated dementia risk, as this could be a modifiable risk factor.

There has already been some research in this area. Dr. Madhav Desai, a gastroenterologist with UTHealth Houston and Memorial Hermann, who was not involved in this research, told Medical News Today:

“There have been several studies on the link between proton pump inhibitors (PPI), which are a common medication for acid reflux and stomach ulcers. Unfortunately, many of these only suggest a link between these two factors, raising anxiety among patients and providers without establishing a clear causation, which remains unknown. The available data does provide us an overview of the problem and an important understanding that any medication should not be blindly prescribed for the rest of the life and should be de-escalated or stopped when the need is decreasing, or there is no ongoing need, respectively. Alternative options should be explored and offered as well.”

The current study was a nationwide population-based study conducted in Denmark. Researchers included almost 2 million participants in their analysis.

Participants were between the ages of 60 and 75 at baseline, in 2000, or due to be turning 60 between 2000 and 2018. Researchers excluded participants who already had dementia or had received treatment with dementia-specific drugs.

During the study time, 99,384 participants developed dementia. Researchers looked at how using proton pump inhibitors was associated with dementia risk. They were able to account for many covariates, including age, sex, level of education, cardiovascular disease, diabetes, high blood pressure, and abnormal lipid levels.

Researchers found a distinct increased risk for dementia among participants under 90 who used proton pump inhibitors.

Among the cases of dementia, 21.2% had at least two proton pump inhibitor prescriptions. In the nested control group, which was made out of dementia-free individuals who used proton pump inhibitors, only 18.9% of participants had at least two proton pump inhibitor prescriptions throughout the study period.

However, the association between dementia and the use of proton pump inhibitors lowered with increased age. So, the increased risk for dementia was highest for the group aged 60 to 69, and lower for older participants.

Study author Dr. Nelso Pourhadi, physician and researcher at the Danish Dementia Research Centre, explained to MNT:

“We found an increased rate of dementia among individuals who had used proton pump inhibitors (PPIs) compared to individuals who had not received the treatment. The rate of dementia was increased regardless of when the treatment was initiated. We found increasing dementia rates with longer duration of treatment.”

This research does have certain limitations. First, it cannot prove that acid-blocking medication use causes dementia. It also only included data from Denmark, meaning that future research ought include data from other countries and populations.

Moreover, the researchers did not have data on proton pump inhibitors use among participants before 1995, which could mean they unintentionally classified certain users as non-users.

Researchers further did not differentiate between certain dementia types. Since proton pump inhibitor use is associated with increased stroke risk, they note that the final association between proton pump inhibitors and dementia could be reflecting this association. However, they believe this is unlikely based on their analysis of participants without stroke.

Furthermore, the study authors note that dementia is often underdiagnosed, and that there is some risk for residual confounding. They also note that they did not have data on lifestyle factors, simply the potential consequences of these factors.

Dr. Pourhadi commented that: “This was an observational study, [and] as such, cannot prove causation. Still, the study results are in line with a number of previous studies in the area, and adds to the mounting evidence on potential long-term serious adverse effects of PPI use.”

He also added:

“As with any other drug, PPIs have side effects, and it is important to focus on reserving the medication for patients with a medical indication for use. Future studies are warranted to determine if there is a causal link between PPI use and dementia risk.”

Dr. Desai noted that despite the study’s limitations, it does point out the importance of cautious medication use. He explained to MNT that “[i]t would be wise to take this medication or any other medication under guidance of your physician and evaluate the need to take it at serial intervals and the indication itself.”

“Many times, these medications are overprescribed for conditions that could have been evaluated further and patients are taking it without any benefit,” he pointed out. “This is not good for our patients and not a good way of practicing medicine either.”

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