The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.
Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
The median follow-up time was 10.3 years.
There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio [aIRR], 1.36; 95% CI, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.
“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors write. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”
Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Copenhagen, Denmark. It was published online October 5, 2023, in Alzheimer’s and Dementia.
The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.
The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.
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