Proton Pump Inhibitors May Raise the Risk of Dementia

In a large study with nearly two million participants, Danish researchers found evidence that suggests proton pump inhibitor medications used to treat acid reflux may increase the risk of dementia.

Previous research has found people taking proton pump inhibitors (PPIs) for more than 4.5 years may have a higher risk of dementia. However, this study was limited and only included 5,712 participants, which left unanswered questions about the relationship between these acid reflux drugs and cognitive decline.

In a new observational study published on October 5 in Alzheimer's & Dementia, researchers from Denmark examined a much larger number of participants and found more links between PPIs and dementia.

To conduct the study, scientists recruited 1,983,785 individuals aged 60 to 75 with a study period between 2000 and 2018 who did not have dementia or never took medications for cognitive impairment.

PPIs are primarily prescribed medications in Denmark. So, the scientists used this data to determine which participants had redeemed at least two prescriptions for PPIs, who only received one prescription, or who had not taken the medications since 1995.

The data showed that, on average, participants who used PPIs started taking them when they were around 68 years old.

At the study's conclusion, the researchers analyzed the data, adjusting for age, sex, education level, and health conditions such as diabetes, cardiovascular disease, and high blood pressure.

During the follow-up period, 99,384 participants developed dementia. Among those with dementia, around 21.2% took at least two PPI prescriptions versus 18.9% in the dementia-free group.

The analysis found that PPI use was associated with an increased rate of dementia.

The incidence of dementia was most pronounced in participants who took PPIs for more than 15 years. Moreover, the increased risk was highest in participants ages 60 to 69 and lower in older individuals.

Why would proton pump inhibitors raise dementia risk?

The scientists suggest that PPIs can affect brain cells through various mechanisms, such as increasing beta-amyloid levels, which may be involved in the development of Alzheimer's disease.

In addition, they note the side effects of PPI use include neurological, psychological, and psychiatric symptoms or conditions.

While the study appears concerning, it did have some limitations. For example, the data included PPI prescriptions starting in 1995. So, data on over-the-counter and in-hospital intravenous use of these medications were not available. This could've led to underestimating PPI use and misclassifying participants who took PPIs and those who didn't.

Although the results only found an association between PPI use and dementia, the authors say more studies are needed to determine if proton pump inhibitors actually cause dementia. They also want to examine these risk differences by age at dementia diagnosis and look into the potential links to different dementia subtypes.