Sildenafil and risk of Alzheimer disease: a systematic review and meta-analysis

Abstract

Background: Alzheimer Disease (AD) affects more than 50 million people worldwide, with 10 million new diagnosis each year. The link between Sildenafil, a Phosphodiesterase-5 (PDE5) inhibitor, and risk of AD has been debated. We conducted the first meta-analysis on the association between Sildenafil use and risk of AD. Methods: We searched MEDLINE and Embase from inception to March 11, 2024 to identify cohort, case-control studies comparing the frequency of AD in patients taking Sildenafil with those without. We computed risk ratios (RR) and hazard ratios (HR) with accompanying 95% Confidence Intervals (CIs) for each study, and pooled the results using a random-effects meta-analysis. Results: Out of 415 studies that were screened initially, 5 studies comprising 885,380 patients were included for analysis. Sildenafil use was associated with a reduced risk of developing AD by two-fold compared to non-use (HR: 0.47, 95% CI: 0.27-0.82, p<0.001). There was a similar association in risk reduction of AD in patients on PDE5 inhibitors compared to non-use (RR: 0.55, 95% CI: 0.38-0.80, p=0.002). Conclusions: Our meta-analysis showed that the use of Sildenafil is associated with a reduced risk of developing AD by two-fold. Further randomized control trials to ascertain the effect of Sildenafil on AD pathology would be useful.