The PPI Dementia Controversy

New Evidence suggesting PPI’s protect against dementia

In this latest study, proton-pump inhibitors were not associated with cognitive impairment.

Patients continue to express concern about media reports stating that proton-pump inhibitor (PPI) use might cause cognitive impairment or dementia. In this latest study, researchers took advantage of prospectively collected data on 10,500 patients (mean age, 73) with normal cognition or mild cognitive impairment who were followed at 33 U.S. Alzheimer disease research centers. Participants underwent detailed structured cognitive assessments annually and were classified as using PPIs continuously, intermittently, or never. Follow-up ranged from 2 to 6 years.

In analyses adjusted for confounding demographic and clinical variables, PPI use (continuous or intermittent) compared with no PPI use was associated with significantly lower risk for progression from normal cognition to mild cognitive impairment, and from mild cognitive impairment to dementia. Hazard ratios for progression were roughly 0.80 for these outcomes. Histamine-2–receptor antagonist use also was associated with lower risk for cognitive impairment.


This study’s strength is its robust longitudinal assessment of cognitive status at specialized research centers; in contrast, the first publicized study to suggest a PPI−dementia connection was derived from an administrative claims database with nonverified dementia diagnoses and inadequate adjustment for confounding variables (NEJM JW Gen Med Jun 15 2016 and JAMA Neurol 2016; 73:410). Although the protective effect of PPIs against cognitive decline found in the current study is difficult to explain, the findings provide reassurance that PPIs are unlikely to cause cognitive decline. A recent Finnish study with confirmation of dementia diagnoses reached similar conclusions (NEJM JW Gen Med Sep 15 2017 and J Gastroenterol 2017 Jul 11;

Allan S. Brett, MD reviewing October 12, 2017 Goldstein FC et al. J Am Geriatr Soc 2017 Sep .