JAMA Neurology suggests that there is a weak association between PPI use and dementia.  Is it real?

The current study is based on information from a pharmaceutical database rather than on medical records. It is a retrospective analysis rather than prospective and therefore cannot be blinded.  The study used the largest mandatory public health insurer in Germany, which includes one third of the overall population and as much as 50% of the elderly population. Its database includes information on diagnoses and drug prescriptions.

The study appears biased owing to the lack of statistical adjustment as it was not adjusted for all confounders. Although the study was adjusted for age, gender, polypharmacy, stroke history, depression, ischemic heart disease, and diabetes, it was not adjusted for well-known risk factors for dementia, including alcohol use, family history of dementia, hypertension and B12 deficiency. Thus, a tremendous amount of potential risk factors that might account for the imbalance of incident dementia between PPI users and nonusers.

The scientific hypothesis was that PPIs may change the development of amyloid plaques which have been associated with dementia. PPIs may alter an enzyme secretase that lays down these plaques in the brain. There is some hypothesis and demonstration that these amyloid plaques are seen in the Alzheimer variant of dementia. The study found of 73,679 subjects aged 75 years or older who initially did not have dementia at baseline, 29,510 subjects were diagnosed with dementia over the course of the study (2004 – 2011). Dementia was categorized just as “Dementia”, but only 2.7% of patients actually had Alzheimer disease. Now recalling how dementia was categorized in this study and that only 2.7% of patients had Alzheimer disease, it’s important to put this percentage into perspective, given this hypothesis that PPIs may change the development of amyloid plaques.

What Should We Tell Our Patients?

Certainly, there are benefits of PPIs, including treatment of severe reflux disease and prevention of bleeding and nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy.

There are a lot of issues with the PPI + dementia data which has created a lot of undue angst.  The statistical association between PPI prescription and occurrence of dementia and does not prove that PPIs cause dementia. To evaluate the cause-and-effect relationships in the elderly, randomized, prospective clinical trials are needed, When carefully analyzed, they really are not anything more than a little bit of noise.

Right now, Gastroenterologists do NOT need to change therapies or prescribing behaviour on the basis of concern about dementia. The benefits of PPI therapy need to be kept in perspective. But if patients don’t need the medication, then longterm use could be reconsidered. Not because we think the patient is going to develop dementia, but they just don’t need the medication. So, if they don’t need the medicine, they shouldn’t take it. If they do need it, you can reassure them to take it. Even a professor of medicine and gastroenterology continues to take PPI therapy after analysing the data.