A recently published study of claims data from a German health plan suggests an association between proton pump inhibitor (PPI) use and dementia in the elderly.

Because the claims data used in the current study lack detailed sociodemographic data, such as diet, lifestyle and education, the researchers could not integrate these important factors into the analysis.

Researchers identified several confounding factors which were significantly associated with increased dementia risk including depression and stroke. Diabetes and taking five or more prescription drugs other than the PPI (known as “polypharmacy”) were also associated with significantly elevated dementia risk. In the analysis, polypharmacy elevated the risk for occurrence of dementia by about 16 percent.

The study authors note that this analysis of administrative data from a health plan in Germany can only provide a statistical association between PPI prescription 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.

In an editorial in JAMA February 15, 2016 that accompanied the German study, Dr. Lewis H. Kuller from the University of Pittsburgh, writes that “…older patients often take many drugs, and the number of drugs taken may be a function of the extent of disease and comorbidities.” According to Dr. Kuller’s editorial, “determinants of both the disease and the factors related to the use of PPIs may also be related to the risk of dementia.” Additionally, other factors such as level of education may confound the results. He notes a very strong inverse association of risk of dementia and education and suggests the possibility that differences in distribution of education for gastrointestinal acid diseases and use of PPIs may account for the association of PPI use and risk of dementia.

Commentary:

This study out of Germany reports a statistical association between the use of proton pump inhibitors such as Prilosec (omeprazole), Nexium (esomeprazole), Protonix (pantoprazole), Prevacid (lansoprazole), Aciphex (rabeprazole) and dementia. The large number of people who have gastroesophageal reflux and take PPI raises concern but the nature and quality of this study are poor and does not prove a causal association between PPI use and dementia. Nonetheless, a growing number of adverse effects have been associated with PPI use to include osteoporosis, hypomagnesemia, and renal insufficiency. This list underscores the need to use the least amount of medication possible to control symptoms of GERD. Chronic use requires the ongoing supervision of your physician. – Raymond W. Phillips, MD