Long-term PPI usage is not linked with an elevated risk of Alzheimer's disease or all-cause dementia.

A real-world distributed network analysis was conducted to determine the relationship between proton-pump inhibitors (PPI) use and all-cause dementia or Alzheimer's disease.

Overall, 41,670 patients (> 18 years of age) out of 7,293,565 participants from 6 cohorts were eligible. Notably, 2206 individuals in total were eliminated, either because they were part of both cohorts or because they had dementia in the past. A total of 5699 propensity-matched pairs of PPI and users of the histamine-2 receptor antagonist (H2RA) were incorporated in the trial after propensity matching.

The occurrence of Alzheimer's disease at least 365 days following exposure to the drug was the major endpoint. The occurrence of all-cause dementia at least 365 days following drug exposure was the secondary endpoint ascertained.

The risk of all-cause dementia or Alzheimer's disease was not statistically different between the H2RA and PPIs groups in the 1:1 propensity score matching across all 6 databases. Contrasted to H2RA users, long-term PPI users (⩾365 days) had no correlation with all-cause dementia (hazard ratio [HR] = 1.04; I2 = 0%) or Alzheimer's disease (HR =0.92; I2 = 0%) in the distributed network analysis.

Physicians must not avoid PPIs because of concerns about dementia risk.