Abstract
The objective of the study was to investigate whether proton pump inhibitor (PPI) use is associated with an increased risk of clinically verified Alzheimer's disease (AD). A Finnish nationwide nested case-control study MEDALZ includes all community-dwelling individuals with newly diagnosed AD during 2005-2011 (N=70,718), and up to four age-, sex-, and region of residence-matched comparison individuals for each case (N=282,858). Data were extracted from Finnish nationwide health-care registers. PPI use was derived from purchases recorded in the Prescription register data since 1995 and modeled to drug use periods with PRE2DUP method. AD was the outcome measure. PPI use was not associated with risk of AD with 3-year lag window applied between exposure and outcome (adjusted odds ratio (OR) 1.03, 95% confidence interval (CI) 1.00-1.05). Similarly, longer duration of use was not associated with risk of AD (1-3 years of use, adjusted OR 1.01 (95% CI 0.97-1.06); ≥3 years of use adjusted OR 0.99 (95% CI 0.94-1.04)). Higher dose use was not associated with an increased risk (≥1.5 defined daily doses per day, adjusted OR 1.03 (95% CI 0.92-1.14)). In conclusion, we found no clinically meaningful association between PPI use and risk of AD. The results for longer duration of cumulative use or use with higher doses did not indicate dose-response relationship.
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