A recent study conducted by researchers from Copenhagen University Hospital and Aarhus University in Denmark has delved into the potential link between proton pump inhibitors (PPIs), commonly used antacid medications aimed at suppressing stomach acid production – and an elevated risk of developing dementia.
Their paper, titled “Proton pump inhibitors and dementia: A nationwide population-based study,” was published in the Alzheimer’s & Dementia journal, revealing notable associations between PPI usage, its duration, and an increased risk of dementia. This comprehensive investigation took place within a nationwide Danish cohort of 1,983,785 individuals aged 60 to 75, spanning from 2000 to 2018.
Notably, this study exclusively included individuals without any prior dementia diagnosis or specific treatments for dementia. Throughout the study period, 99,384 individuals from the cohort developed dementia, while 469,920 served as a control group. The research uncovered that PPI usage correlated with an elevated risk of all-cause dementia, with a particular emphasis on those individuals aged 60 to 69 at diagnosis.
In this age group, the incidence rate ratio ranged from 1.25 to 1.59, depending on the duration of PPI use, and an overall incidence rate ratio of 1.36 was observed for those who had ever used a PPI. The risk was somewhat lower for individuals aged 70 to 79 and 80 to 89, with incidence rate ratios of 1.12 and 1.06, respectively, for ever using PPIs. Notably, no significant association between PPI usage and dementia was found for individuals over the age of 89 at the time of diagnosis.
Importantly, PPI exposure was linked to an increased incidence of all-cause dementia, especially in individuals under 90 years of age, irrespective of when PPI treatment began. Moreover, it was observed that longer cumulative durations of PPI use were associated with higher risk estimates. Proton pump inhibitors are widely prescribed to treat conditions related to excessive gastric acid production.
However, prior studies have yielded conflicting results concerning the potential connection between PPI use and dementia. Some research has suggested possible neurological adverse effects related to PPIs, including impacts on brain neurotransmitters, yet the exact mechanisms and causality behind these effects remain unclear. The findings from this study indicate that PPI usage is associated with an elevated risk of dementia, particularly among younger individuals.
However, it’s important to note that this doesn’t establish a direct causal link between PPIs and dementia. It’s plausible that reverse causality is at play, meaning that increased stomach acid production might occur early in the development of dementia, prompting the use of PPIs to address symptoms of a disease already in progress. Alternatively, PPI treatments might be causing disruptions that ultimately lead to dementia.
The enteric nervous system, a network of neuronal cells embedded in the gastrointestinal system, plays a pivotal role in the gut-brain connection, and disruptions in one system may affect the other. Additionally, correlations have been identified between Alzheimer’s disease and specific gut microbiota populations, further complicating efforts to establish causal relationships.
Considering these complex findings, the authors of the study emphasize the need for additional research to delve into the mechanisms underlying this association and whether it varies among different subtypes of dementia. Further exploration of this topic is essential to gain a more comprehensive understanding of the potential links between PPI usage and dementia, shedding light on potential factors and mechanisms that could be at play in this intriguing relationship.
Reference
Nelsan Pourhadi et al, Proton pump inhibitors and dementia: A nationwide population‐based study, Alzheimer’s & Dementia (2023). DOI: 10.1002/alz.13477/.
