The first meta-analysis on the association between use of sildenafil, a Phosphodiesterase-5 (PDE5) inhibitor, and risk of Alzheimer’s disease (AD) was conducted by Singaporean researchers. MEDLINE and Embase were searched from inception to March 11, 2024 to identify cohort, case-control studies comparing the frequency of AD in patients taking sildenafil with those without. Risk ratios (RR) and hazard ratios (HR) were computed with accompanying 95% confidence intervals (CIs) for each study, and the results pooled using a random-effects meta-analysis.

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 53% 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). Although the meta-analysis showed that the use of sildenafil is associated with a reduced risk of developing AD, further randomized control trials to ascertain the effect of sildenafil on AD pathology would be useful.

References

Chua WY, et al. Aging (Albany NY). 2025;17(3):726-39.