Can proton pump inhibitors (PPI) cause dementia?

Proton pump inhibitors (PPIs) are widely used by head and neck cancer patients (including laryngectomees). PPIs have been shown to be potentially involved in cognitive decline including dementia. The use of PPIs has also been associated with chronic renal disease, and myocardial infarction.

A prospective cohort study from Germany evaluated 73 679 individuals 75 years of age or older that were treated with PPIs (omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole) from 2004 to 2011. Those receiving regular PPI medication had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication. This finding is supported by recent analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. 

A significant association of previous and current PPI use with vitamin B12 deficiency was found in a previous study in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance β-amyloid (Aβ) levels in the brains of mice by affecting the enzymes β- and γ-secretase. However, the underlying mechanism by which PPIs might influence the development of dementia is yet to be determined.

The authors concluded that avoidance of PPI medication may prevent the development of dementia. Randomized, prospective clinical trials are needed to examine this connection in more detail.