Minneapolis, MN—Does longer-term use of proton pump inhibitors (PPIs) increase the risk for dementia? A new study suggested that might be the case, demonstrating an association in patients who used the acid reflux medication for 4.5 years or more.

The report in Neurology does not actually prove that cumulative PPI use causes dementia; previous studies have provided contradictory evidence.

“Proton pump inhibitors are a useful tool to help control acid reflux, however, long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”

“Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use,” the study team wrote. “We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study.”

The analyses involved participants from a community-based cohort (ARIC) from the time of enrollment (1987-1989) through 2017. PPI use was assessed via visual medication inventory at clinic Visits 1 (1987-89) to 5 (2011-2013) and reported annually in study phone calls (2006-2011). “The present study uses ARIC Visit 5 as baseline, since this was the first visit in which PPI use was common,” the authors noted in the report. “PPI use was examined two ways: current use at Visit 5 and duration of use prior to Visit 5 (Visit 1 to 2011, exposure categories: 0 days, 1 day-2.8 years, 2.8-4.4 years, >4.4 years). The outcome was incident dementia after Visit 5.”

The study included 5,712 dementia-free participants at Visit 5; members of the group had a mean age of 75 years, 22% were black, and 58% were female. With a median follow-up of 5.5 years, the minimum cumulative PPI use was 112 days, and the maximum use was 20.3 years.

“There were 585 cases of incident dementia over median follow-up time,” the authors stated. Although participants using PPIs at Visit 5 were not at significantly higher risk for developing dementia during subsequent follow-up compared with non-users (hazard ratio [HR]: 1.1; 95% CI, 0.9-1.3), those who used PPIs for >4.4 cumulative years prior to Visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3; 95% CI, 1.0-1.8) than those reporting no use. “Associations were not significant for lesser amounts of PPI use,” according to the researchers.

The researchers stated that their study provides class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older called for future studies to better understand possible pathways between cumulative PPI use and the development of dementia.

“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” Dr. Lakshminarayan advised. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”

A limitation of the study was that because participants were asked about medication use once yearly, their use between annual check-ins was estimated. The authors were also unable to assess whether participants took OTC acid-reflux drugs.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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