Researchers from Copenhagen University Hospital and Aarhus University, Denmark, have investigated the possible link between proton pump inhibitors (PPIs), commonly used antacids to suppress stomach acid production, and an increased risk of dementia.
In a paper entitled “Proton pump inhibitors and dementia: A nationwide population-based study”, published in Alzheimer’s & Dementia, the researchers find significant associations between PPI use, duration of use and increased risk of dementia.
The study was conducted in a nationwide Danish cohort of 1,983,785 people aged 60-75 years between 2000 and 2018, and included only people without a previous diagnosis of dementia or treatment with dementia-specific drugs.
During the study, 99,384 people developed dementia and 469,920 were used as controls. PPI use was associated with an increased risk of all-cause dementia, especially in people aged 60 to 69 years at diagnosis. In the 60-to-69-year-old group, the incidence rate ratio was 1.25 to 1.59, depending on duration of use, and 1.36 overall for those who had ever used a PPI.
A lower risk was seen in the 70-79 and 80-89 groups, with RRs of 1.12 and 1.06 for ever use, respectively. No significant association between PPI use and dementia was observed in people over 89 years of age at diagnosis.
PPI exposure was associated with an increased rate of all-cause dementia before the age of 90, regardless of when PPI treatment started. A longer cumulative duration of PPI use resulted in higher risk estimates.
PPIs are commonly used to treat acid-related disorders of the stomach. Previous studies have shown conflicting results about the association between PPI use and dementia. PPIs have been associated with possible neurological adverse effects, including effects on brain neurotransmitters, although the mechanisms and causality are unclear.
The evidence suggests that PPI use is associated with an increased risk of dementia, especially in younger people. This does not mean that PPI use causes dementia, as there is a possibility of reverse causality, where acid production in the stomach is increased early in the development of dementia and PPI treatments are used to treat the symptom of a disease that is already progressing. It is also possible that PPI treatment causes a disorder that leads to dementia.
The enteric nervous system, the nerve cells embedded in the walls of the gastrointestinal system, is an essential part of the gut-brain connection, and it is possible that disturbances in one could affect the other. Associations have also been found between Alzheimer’s disease and specific gut microbiota populations, which could further confound causal relationships.
The authors suggest that further research is needed to explore the mechanisms underlying this association and whether it varies between dementia subtypes.
