Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.
“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.
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Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.
To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.
In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.
The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).
Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.