A widely used medication prescribed for acid reflux may raise the risk of developing dementia when taken long-term, according to a recent study published in Neurology, the journal of the American Academy of Neurology. The research indicates that individuals using proton pump inhibitors (PPIs) for more than 4.4 years could face a 33% greater likelihood of dementia compared to those who have never used the drugs.
The 2023 study involved 5,712 participants aged 45 and above, all initially dementia-free, with an average age of 75. Researchers examined PPI usage, which includes drugs that suppress stomach acid by blocking enzymes responsible for acid secretion. Approximately 26% (1,490) of participants had taken PPIs.
Participants were grouped by duration of use: never users; those using PPIs for up to 2.8 years; between 2.8 and 4.4 years; and over 4.4 years. Acid reflux, a condition causing stomach acid to flow back into the oesophagus and result in heartburn or ulcers, can escalate to gastro-oesophageal reflux disease (GORD), linked with risks such as oesophageal cancer.
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While PPIs effectively manage acid reflux symptoms, prior studies have associated long-term use with increased risks of stroke, bone fractures, and chronic kidney disease. Kamakshi Lakshminarayan, MBBS, PhD, lead author and University of Minnesota epidemiologist, noted, “Although short-term use showed no increased dementia risk, long-term usage was correlated with higher incidence.”
Over an average follow-up of 5.5 years, 585 participants developed dementia—about 10% of the cohort. Among those who never used PPIs, the dementia rate was 19 cases per 1,000 person-years, compared to 24 cases per 1,000 person-years in the group using PPIs for more than 4.4 years.
After adjusting for factors such as age, sex, race, blood pressure, and diabetes, the study concluded a significant 33% increased risk of dementia among long-term PPI users. Importantly, no increased risk was observed for those on the drugs less than 4.4 years.
The study does not establish causation but highlights an association requiring further investigation. Researchers emphasized that while alternative strategies for managing acid reflux—like antacids, weight management, and dietary adjustments—exist, these may not be effective for everyone. They advise patients to consult healthcare providers before altering or discontinuing PPI treatment, as abrupt cessation may worsen symptoms.
Limitations include yearly medication tracking, which may not capture exact usage patterns, and the inability to account for over-the-counter PPI consumption. The research was funded by the National Institutes of Health.