Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies

Abstract To evaluate the potential therapeutic benefits of phosphodiesterase-5 inhibitors (PDE5Is) on Alzheimer’s disease (AD), electronic databases Embase, Scopus, and Medline were systematically searched from inception to March 18th, 2024. Studies assessing the association between the use of PDE5Is and AD incidence were included. Random-effects model of restricted maximum likelihood estimator was used to pool data. Seven studies were reviewed comprising 4,833,558 individuals, of which 348,546 received treatment with one of the PDE5Is. Pooled hazard ratios (HR) for AD incidence, comparing PDE5Is with no drug use (HR = 0.47, 95% CI 0.26–0.82, p -value: 0.01), and PDE5Is with no drug or drugs not in trial for AD (HR = 0.41, 95% CI 0.33–0.52, p -value: <0.01) were calculated. Synthesized evidence indicates PDE5Is administration is associated with AD risk reduction, supporting conduct of phase 3 clinical trials.