Proton-Pump Inhibitors (PPIs) and Increased Risk of Dementia

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Proton-Pump Inhibitors (PPIs) in Long-term Care

Late last year, we reported on mounting evidence of adverse drug events associated with PPIs:

Drug Interactions
PPIs are implicated in a number of clinically significant drug interactions including a 20-40% reduction in antiplatelet activity when clopidogrel (Plavix) is used with omeprazole or esomeprazole.  Use of these PPIs with clopidogrel is contraindicated per product labeling.  Also, because they lower gastric pH (acidity) they may reduce the absorption of calcium, iron, magnesium, and Vitamin B-12.  If calcium must be given with a PPI, the calcium citrate formulation is recommended as its absorption is less affected by the higher gastric pH produced by PPIs.

Safety Concerns
There is concern that PPIs may increase fracture risk in both men and women with one study suggesting a 25% increase in overall fractures and a 47% increase in spinal fractures in postmenopausal women.  Any patient who must remain on long-term PPI therapy who is a risk for factures (i.e. osteoporosis or osteopenia) should receive supplementation with adequate doses of calcium citrate and Vitamin D. 

PPIs also increase the risk of infection with bacteria including Clostridium difficile and those causing pneumonia that tend to proliferate when gastric pH remains elevated.  In fact, patients being treated for C. difficile infections while taking a PPI are at a 42% increased risk for recurrent infection within 90 days.


In February of this year, a study published in JAMA Neurology points to an association between PPIs and an increased risk for dementia.  The prospective cohort study conducted by the largest German statutory health insurer showed that taking PPIs was associated with “a significantly increased risk of incident dementia compared with not taking them (hazard ratio 1.44, 95% CI, CI 1.36 to 1.52 (P<0.001).  This study included 73,679 participants age 75 and older who were free of dementia at baseline.  This finding was most pronounced in men and those taking esomeprazole.

There is some evidence to support this association as PPIs are known to cross the blood brain barrier.  Animal studies have shown an increase in the production and degradation of amyloid in the brain, in addition to binding tau protein while on PPI therapy.  There is also evidence from human trials that these drugs can reduce circulating levels of B-12 and other nutrients which may also increase the risk for dementia.

While these finding suggest that avoiding PPIs might prevent the development of dementia, the study authors noted that randomized prospective clinical trials are needed before making such a recommendation.

Your AlixaRx Clinical Pharmacist can work with your QAPI team and facility prescribers to identify patients on long-term treatment with PPIs without a clear indication for continued treatment and recommend alternative therapies and/or a gradual dose reduction to limit the risk for adverse drug events. PPIs should not be discontinued abruptly as this may cause rebound hyperacidity.





This article was originally published in our monthly issue of From the Front Lines – a monthly publication that shares best practices and medication-related challenges faced by “front line” staff in long-term care and post-acute (LTCPAC) facilities.

>>> From the Front Lines – March 2016 <<<