Proton Pump Inhibitors (PPIs) and Dementia

In early February 2016, there were multiple news reports about proton pump inhibitors (one of the classes of medications we use to treat acid reflux) and dementia risk in the elderly. The media attention came from an observational study led by Willy Gomm, PhD, of the German Center for Neurodegenerative Diseases.

Background of Study:

The researchers from this study examined a German insurance claims database that included over 73,000 people, 75 and older, and free of dementia at the beginning of the study. They found out that over 7 years those who took PPIs long term had a 44% increased probability of receiving a diagnosis of dementia (reported as a hazard ratio of 1.44).

The data from this study has brought up a lot of questions and concerns from patients already on PPI medications. As such, I think it is important to interpret the study a little further.

Interpretation of Study:

First off, the study authors themselves note this analysis of administrative data can only provide a statistical association between PPIs and occurrence of dementia and does not prove that PPIs cause dementia. They recognize that in order to evaluate the cause and effect relationships in the elderly, more research in the form of randomized, prospective clinical trials is needed. Because the claims data used in the current study lacked sociodemographic data, such as diet, lifestyle and education, the researchers could not integrate these important factors into the analysis.

The authors adjusted for some variables, but certainly not all confounders. They adjusted for age, gender, polypharmacy, stroke history, depression, ischemic heart disease, and diabetes. They did not, however, adjust for some very important known risk factors for dementia, including alcohol use, family history of dementia, and hypertension. These are well known risk factors for dementia, and for some reason, these weren’t included in the analysis. Thus, this study misses a tremendous amount of potential risk factors that might account for the imbalance of incident dementia between PPI users and nonusers.

In summary, there seem to be several potential biases owing to the lack of statistical adjustment for key risk factors for dementia. While the data in this study is appreciated, more research is needed to understand the impact of PPIs on cognitive function since studies of this type do not control for diet or lifestyle factors, nor do they establish causation.

What this means for our patients:

This study is important because it provides a healthy platform for the patient and physician to have a discussion regarding the use of PPI (not because we think the patients are going to develop dementia, but because perhaps, they just don’t need to be on the medication long-term). We as the physicians recognize that PPIs are highly effective in treating acid-related disorders and also that there are few hard indications for long-term PPI use, including truly refractory reflux disease, Barrett’s esophagus, Zollinger-Ellison syndrome, idiopathic ulcers and, arguably, as prophylaxis against bleeding in select patients. If the PPI is prescribed for one of these clear-cut indications, then we can reassure patients that the benefits certainly outweigh any risks. If the medication is no longer needed, we will work to wean off appropriately, and recommend life-style medications that may reduce or eliminate the need for PPIs for long-term use. When patients require long-term use of PPIs, the medication should not be stopped without a discussion with the physicians about the risks and the benefits. We always encourage open conversation channels with our patients. If you have any questions about your medications, please let us know.

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