Proton pump inhibitor (PPI) use was modestly associated with incident dementia in older adults (pooled HR = 1.18), but the strength and specificity of this association depended substantially on comparator selection and handling of time-related bias. In the meta-analysis of 23 longitudinal observational studies of older adults without dementia at baseline, dementia risk did not differ significantly between PPI users and users of histamine-2 receptor antagonists (H2RAs) (HR = 1.04); however, a post hoc analysis found that H2RA use itself was associated with dementia (HR = 1.44), and excluding H2RA-treated patients strengthened the PPI estimate (HR = 1.75). Estimates also varied by method used to address time-related bias—lag time (HR = 1.25) versus time-varying exposure (HR = 1.38). Well-designed, long-term studies using active comparators are needed to clarify whether this effect is PPI-specific. Source: https://ascpt.onlinelibrary.wiley.com/
