Spotlight on PPI use and cognition

Studies published in July found no unfavorable association between proton-pump inhibitor (PPI) use and cognitive function.


Two studies this month assessed the effect of proton-pump inhibitor (PPI) use on cognitive function and found no unfavorable association.

In the first study, researchers used data from 13,864 participants in the Nurses' Health Study II to assess the association between PPI use and performance in tests of cognitive function. Participants had each completed a self-administered computerized neuropsychological test battery and provided prospective data on medication use and other potential risk factors.

Using multivariable linear regression models, researchers assessed the associations between PPI use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition.

Results were published online on July 18 by Gastroenterology.

Regular PPI use was associated with trends toward poorer scores in all three cognitive domains, but the only significant association was between longer duration of PPI use and scores for psychomotor speed and attention (mean score difference for 1 to 4 years of PPI use vs. never users, 0.00 [95% CI, −0.04 to 0.04]; 5 to 8 years, −0.03 [95% CI, −0.08 to 0.03]; and 9 to 14 years, −0.06 [95% CI, −0.11 to 0.00]; P=0.03 for trend). However, the magnitude of difference was attenuated after controlling for use of H2-receptor antagonists.

The authors noted limitations of the study, such as the possibility that their analysis lacked power to detect a more modest reduction in cognitive function. They added that uncontrolled or residual confounding could have influenced the results.

“[W]e did not observe a convincing association between use of PPIs and cognitive function in middle-aged and older women,” they wrote. “Our data should provide some reassurance to individuals who require these highly effective medications for long-term treatment.”

Results of a different study, published online on July 11 by The American Journal of Gastroenterology, found no clinically meaningful association between PPI use and the risk of Alzheimer's disease.

Researchers used data from Finnish health care registers to examine the association between PPI use and the risk of Alzheimer's disease. As part of a nationwide nested case-control study of all community-dwelling individuals with newly diagnosed Alzheimer's disease from 2005 through 2011(n=70,718), they matched up to four comparison individuals for each case based on age, sex, and region of residence (n=282,858).

Compared with no PPI use, PPI use (with a three-year lag window applied between exposure and outcome) was not associated with risk of Alzheimer's disease (adjusted odds ratio [OR], 1.03; 95% CI, 1.00 to 1.05). Longer duration of use was not associated with risk of Alzheimer's disease (1 to 3 years of use: adjusted OR, 1.01 [95% CI, 0.97 to 1.06]; ≥3 years of use: adjusted OR, 0.99 [95% CI, 0.94 to 1.04]).

Higher-dose use (≥1.5 defined daily doses per day) was also not associated with an increased risk (adjusted OR, 1.03; 95% CI, 0.92 to 1.14). The reference values for defined daily dose were 30 mg for esomeprazole, 30 mg for lansoprazole, 20 mg for omeprazole, 40 mg for pantoprazole, and 20 mg for rabeprazole.

Limitations include a lack of information on family history of Alzheimer's disease and the severity of comorbid conditions. In addition, changing the lag window led to inconsistent yet sometimes statistically significant results that did not appear to be clinically meaningful, the study authors noted.