Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

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Background & Aims: Studies of association between use of proton pump inhibitors (PPI) and dementia have yielded conflicting results. We investigated the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark. Methods: In a prospective study, we collected data from surveys of middle-aged individuals (46–67 years old; the Middle Aged Danish Twin study) and older individuals (the Longitudinal Study of Aging Danish Twins) who underwent cognitive assessments (a 5-component test battery) over a 10-year period (middle-age study, n = 2346) or a 2-year period (longitudinal study of aging: n = 2475). We determined cumulative use of PPIs 2 years prior study enrollment and during follow up, in defined daily doses (DDDs) of PPIs, using data from a nationwide prescription register. Multi-variable linear regression models were used to examine associations between cumulative PPI use and a composite score of cognitive function at baseline and decreases in scores during the follow-up periods. Results: Use of PPIs before study enrollment was associated with a slightly lower mean cognitive score at baseline in the middle age study. The adjusted difference in mean score of individuals with high consumption of PPIs (≥400 DDD) was lower than that of non-users in the middle-age study (mean crude score for high PPI use, 43.4 ± 13.1 vs for non-use, 46.8 ± 10.2; adjusted difference of 0.69 points; 95% CI, –4.98 to 3.61). In the longitudinal study of aging twins, individuals with high consumption of PPI had higher adjusted scores than non-users (mean crude score for high PPI use, 35.2 ± 10.8 vs for non-use, 36.2 ± 11.1; adjusted difference of 0.95 points; 95% CI, –1.88 to 3.79). In analyses of cognitive decline, among individuals with high consumption of PPIs in the longitudinal study of aging, the adjusted mean difference between baseline score and follow-up score was lower than that of non-users (mean crude score for high PPI use at baseline, 36.6 ± 10.1 and at follow up, 34.3 ± 12.3 vs for non-use at baseline, 38.1 ± 10.5 and at follow up, 37.6 ± 11.3; adjusted difference of –1.22 points; 95% CI, –3.73 to 1.29). In the middle-age study, users with the highest consumption of PPIs (≥1600 DDD) had slightly less cognitive decline than non-users (baseline mean crude score for high PPI use, 43.4 ± 10.1 and follow-up mean crude score, 41.3 ± 9.7 vs baseline score of 49.1 ± 10.2 for non-users and follow-up score of 46.3 ± 9.9 for non-users; adjusted difference of 0.94 points; 95% CI, –1.63 to 3.50). No stated differences in scores between PPI users and non-users were significant. Conclusions: In analyzing data from 2 large population-based studies of twins in Denmark, we found no association between PPI use and cognitive decline.

Original languageEnglish
JournalClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Issue number5
Pages (from-to)681-689
Publication statusPublished - May 2018


  • acid-related diseases
  • epidemiology
  • side-effects
  • treatment


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