Regular Proton Pump Inhibitor Use Associated with an Increased Risk of Dementia in the Elderly

EBM Focus - Volume 11, Issue 8

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Reference - JAMA Neurol 2016 Feb 15 early online (level 2 [mid-level] evidence)

  • The use of proton pump inhibitors (PPIs) to treat gastroesophageal reflux disease and peptic ulcer disease in elderly patients is increasing even though increasing evidence suggests PPI use is associated with an increased risk of adverse events.
  • A recent study in Germany found regular use of prescription PPIs was associated with an increased risk of dementia compared to no PPI use in persons ≥ 75 years old.
  • These results suggest PPI use in elderly patients should be routinely reviewed and stopping unnecessary PPIs may decrease potential harms.

PPIs are commonly used to treat gastroesophageal reflux disease and peptic ulcer disease. PPIs are widely available as both prescription and over-the-counter medications and their use has been steadily increasing in certain populations, especially the elderly (Pharmacoepidemiol Drug Saf 2010 Oct;19(10):1019, BMJ 2008 Jan 5;336(7634):2). However, a growing body of evidence has found an increased risk of adverse effects associated with use of PPIs including bone fractures, cardiovascular events, acute nephritis and infection, and mortality (PLoS One 2015;10(6):e0124653, Clin Gastroenterol Hepatol 2006 May;4(5):597, Am J Gastroenterol 2013 Mar;108(3):308, JAMA Intern Med 2013 Apr 8;173(7):518). Recently, a large observational study from Germany examined whether long-term prescription PPI use was associated with an increased risk of dementia in the elderly.

Medical records of 73,679 persons ≥ 75 years old without dementia were reviewed. Two-thousand nine-hundred fifty persons (4%) were taking regular PPI medication, defined as at least 1 PPI prescription in each quarter of an 18-month interval. The data was adjusted for confounding factors including age, sex, polypharmacy (≥ 5 prescription medications besides PPI), stroke, depression, ischemic heart disease, and diabetes. Overall, 40% of the study population developed dementia. Compared to no PPI use, regular PPI use was associated with an increased risk of incident dementia (adjusted hazard ratio 1.44, 95% CI 1.36-1.52). These results were consistent in subgroup analyses of women and men, and subgroup analyses by age found the risk of dementia with PPI use decreased with increasing age.

The findings of this study suggest that regular PPI use by the elderly may be associated with an increased risk of dementia. This study agrees with previous findings from another German longitudinal study in elderly patients which found an increased risk of dementia with PPI use (Eur Arch Psychiatry Clin Neurosci 2015 Aug;265(5):419). Several limitations should be considered when interpreting this study. First, it is not clear whether there were persons taking over-the-counter PPIs. Second, the ApoE4 allele status and educational level of the persons in the study was not known, and these factors could also potentially influence the magnitude of risk. Finally, baseline rates of mild cognitive impairment, a major risk factor for dementia, were not assessed. While this study is not conclusive, it is one more reason to routinely review whether elderly patients taking PPIs need to continue them. Stopping unnecessary PPIs may save money and decrease harms.

For more information, see the Gastroesophageal reflux disease (GERD) and Alzheimer dementia topics in DynaMed Plus. DynaMed users click here and here.