2016-02-18 15:03:22 UTC

How to Talk with Your Patients About PPIs and Cognitive Decline

Feb. 22, 2018

More information clearing concerns about the use of proton pump inhibitors (PPIs).

**Updated February 2018 per new research.

A 2018 study published in Clinical Gastroenterology and Hepatology (CGH), “Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline,” found no association between PPI use and cognitive decline in analyzing data from two large population-based studies.

In the last few years, this area of research has received increased attention from both the medical community and patients alike. Here are some notes on interpreting noteworthy studies analyzing PPI and cognitive health and what patients need to know.


The 2018 study in CGH, “Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline,” investigated the effects of PPIs on cognitive decline in middle-aged and elderly twins in Denmark. The prospective study, the Middle Aged Danish Twin study and the Longitudinal Study of Aging Danish Twins, collected survey data from middle aged and older individuals, who underwent cognitive assessments over a 10-year period or a two-year period. Ultimately, no stated differences in scores between PPI users and non-users were significant.

A 2017 study published in Gastroenterology, "Association Between Proton Pump Inhibitor Use and Cognitive Function in Women," did not find convincing data that shows PPI use increases the risk of dementia. The study looked at 13,864 participants from the Nurses’ Health Study II who completed testing on cognitive function, which is key predictor of the risk of dementia later in life. The study did not find convincing evidence that PPI use was associated with cognitive function and refutes the suggestion of the 2016 study that PPI use increases dementia risk. 

A 2016 study published in JAMA Neurology,Association of Proton Pump Inhibitors With Risk of Dementia,” initially raised questions among patients and health care professionals. The study, from Germany, is based upon insurance claims data and demonstrates a statistical association of dementia and long-term PPI use, not causation. Additional studies will need to be performed to prove that avoiding PPIs prevents dementia from developing.

Clinicians should recognize that PPIs are highly effective in treating acid-related disorders and also that there are few hard indications for long-term PPI use, including truly refractory GERD (with an abnormal pH study), Barrett’s esophagus, Zollinger-Ellison syndrome, idiopathic ulcers and, arguably, as prophylaxis against bleeding in select patients. 

Patients taking PPIs for a diagnosed medical condition can be reassured by newer evidence, as well as the continued research on long-term PPI use. The key points about safely using PPIs remain the same. 

Talking to Your Patients

  1. Reassure patients that you prescribed a PPI for a clear-cut indication, in the lowest possible dose, and for an appropriate period of time (lowest dose, shortest time). This advice echoes that offered by AGA and ABIM in the Choosing Wisely campaign. 
  2. Educate patients not to ask “what side effects do PPIs have?” but rather “is it really indicated?” Reassure patients that, when PPIs are indicated, benefits outweigh risks.
  3. Keep conversation channels open with patients. When patients require long-term use of PPIs, the medication should not be stopped without a discussion with you about the risks and benefits. 
  4. Recommend that patients also consider life-style modifications that may reduce or eliminate the need for PPIs for long-term use, as was concluded in the study “Lifestyle Intervention in Gastroesophageal Reflux Disease.”

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