From the Guidelines
Proton pump inhibitors (PPIs) have been associated with cognitive changes in some patients, particularly in elderly patients with prolonged use, and it is recommended to consult a healthcare provider about alternative treatments such as H2 blockers or lifestyle modifications if cognitive symptoms occur. The connection between PPIs and cognitive changes is not fully understood, but it may involve vitamin B12 deficiency due to decreased acid production affecting absorption, disruption of the gut microbiome which impacts the gut-brain axis, or potential crossing of the blood-brain barrier affecting neurotransmitter function 1. Some studies have investigated the relationship between PPI use and vitamin B12 status in older populations, finding that duration and dosage of PPI use may be key effect modifiers 1. For example, a large, nested case-control study found that a mean daily PPI dose of >1.5 pills had a stronger association with vitamin B12 deficiency compared with <0.75 pills/day 1. Regular medication reviews, especially for elderly patients on long-term PPI therapy, are important to minimize these potential cognitive effects. Key considerations for minimizing cognitive effects include:
- Monitoring vitamin B12 levels in patients on long-term PPI therapy
- Considering alternative treatments such as H2 blockers or lifestyle modifications for patients experiencing cognitive symptoms
- Optimizing PPI dosage and duration of use to minimize potential adverse effects 1. It is essential to weigh the benefits and risks of PPI use and to consider individual patient factors, such as age and comorbidities, when making treatment decisions 1.
From the Research
Association Between PPI Use and Cognitive Changes
- The relationship between proton pump inhibitor (PPI) use and cognitive changes is complex and has been investigated in several studies 2, 3, 4, 5, 6.
- Some studies suggest that PPI use may be associated with an increased risk of cognitive impairment and dementia 5, 6.
- For example, a study published in 2023 found that time-varying use of PPIs was associated with an increased risk of dementia, with a hazard ratio of 1.85 (1.80-1.90) 5.
- Another study published in 2017 found that PPI use was associated with severe cognitive impairment in a cohort of World Trade Center responders, with an adjusted odds ratio of 1.67 (1.054-2.643) 6.
Studies with Null or Inconsistent Findings
- However, not all studies have found a significant association between PPI use and cognitive changes 3, 4.
- A study published in 2017 found that continuous PPI use was actually associated with a lower risk of decline in cognitive function, with a hazard ratio of 0.78 (0.66-0.93) 3.
- Another study published in 2017 found no convincing association between PPI use and cognitive function in a cohort of women 4.
Potential Mechanisms and Confounding Variables
- The potential mechanisms underlying the association between PPI use and cognitive changes are not fully understood, but may involve the effects of PPIs on the gut-brain axis or the presence of confounding variables such as posttraumatic stress disorder (PTSD) 6.
- Further research is needed to clarify the relationship between PPI use and cognitive changes, and to identify potential strategies for mitigating any adverse effects of PPIs on cognitive function 2, 3, 4, 5, 6.