Proton pump inhibitor use may increase dementia risk (2)

According to Pharmacy Today magazine, concerns are being raised about the risk of serious adverse effects due to the long-term use of proton pump inhibitors (PPIs) by geriatric patients. Although PPIs are among the most commonly used acid-suppressive therapies in the U.S., chronic PPI use has recently been associated with the risk of hip fracture, community-acquired pneumonia, Clostridium difficile infection, interstitial nephritis, hypomagnesemia, and myocardial infarction. In addition, data from two new German trials indicates that chronic PPI use by older adults may increase the risk of developing dementia:

  • The first trial was a database study in patients aged 75 years and older with no dementia diagnosis. The authors evaluated the incidence of Alzheimer's disease (AD) dementia and incident dementia in 3,076 patients who used PPIs during an 18-month follow-up period. The trial controlled for various confounders, such as age, sex, education, polypharmacy, anticholinergic drugs, and comorbidities. Those using PPIs had a significant increase in the incidence of any dementia and of AD dementia.

  • A subsequent trial evaluated the incidence of dementia with chronic PPI use over 18-month intervals in a similar cohort of more than 73,000 patients aged 75 years and older. The trial controlled for confounders similar to those in the first trial. In the 2,950 patients (with a mean age of 83) who used PPIs regularly, a significant increase in the incidence of any dementia was observed. Several factors were identified that significantly increased dementia risk with PPI use, including male gender, depression, stroke, diabetes, and polypharmacy.

The results of these trials appear to indicate an association with PPI use and an increased risk of developing dementia. Some data also suggest that PPIs can alter the beta or gamma secretase, which is involved in development of beta-amyloid plaques in the brain, representing a key pathophysiologic change seen in AD. Thus, there is a potentially plausible explanation for the association. In addition, some evidence suggests that reductions in vitamin B12 absorption occur with chronic PPI use, particularly in older adult patients.

PPIs should be avoided for geriatric patients
PPIs are already listed in the Beers criteria as potentially inappropriate medications for use in seniors because of the risk of hip fracture and Clostridium difficile infection. The recent trials provide further evidence that PPIs should be avoided for geriatric patients. If necessary, a Symbria Rx Services pharmacist can provide assistance in helping residents at our client communities withdraw from PPI therapy, recommend alternate therapies, and reduce the medication burden for residents using polypharmacy.

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