Evidence Hub

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

Chua WY, Lim LKE, Wang JJD, Mai AS, Chan LL, Tan EK

Aging, 2025

885,380 participants · 3 citations

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.

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 885,380 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

Read the paper

Related studies

Go deeper in Evidence Hub

Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.

Open this study Sign up free