The review by Eusebi et al. (2017) delves into the long-term effects of proton pump inhibitors (PPIs), with a specific focus on their potential influence on brain health and risk of dementia. PPIs are commonly prescribed for acid-related conditions, yet their prolonged use has raised concerns about adverse effects, including cognitive impacts. Emerging research suggests that PPIs may contribute to increased dementia risk, especially in older adults. The authors explore how PPIs might influence amyloid metabolism, a process crucially involved in Alzheimer's disease. Animal studies have shown that PPI use can lead to higher levels of amyloid-beta in the brain, similar to the pathological deposits found in Alzheimer's patients. Additionally, prolonged PPI use is associated with vitamin B12 deficiency, which has been linked to cognitive impairment. This connection between nutrient absorption and cognitive function is particularly concerning, as vitamin B12 is essential for maintaining healthy nerve cells and supporting overall brain health.

The article notes that the clinical evidence linking PPIs to dementia is mainly derived from observational studies, which makes it difficult to establish a direct causal relationship. For instance, a large observational study found that elderly PPI users had a higher risk of dementia, but these findings have not yet been consistently replicated in randomized controlled trials (RCTs), which provide stronger evidence. The review emphasizes that more rigorous, controlled studies are needed to clarify whether PPIs themselves increase dementia risk or if other factors-such as age, preexisting health conditions, or polypharmacy-are contributing to these outcomes. Until more definitive research is available, the authors advise caution in prescribing PPIs, particularly for older patients who may already be vulnerable to cognitive decline.

Overall, the review highlights the need for greater awareness of the potential neurological risks associated with long-term PPI use, especially as the population ages and the prevalence of dementia rises. By shedding light on these possible cognitive side effects, the authors call for healthcare providers to carefully consider the duration and necessity of PPI treatment in patients at risk for dementia. While PPIs remain effective for managing acid-related disorders, their influence on brain health underscores the importance of exploring alternative therapies or using the lowest effective dose to mitigate potential harm. This cautious approach could play a crucial role in preserving cognitive health and reducing dementia risk among vulnerable populations.