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Research Paper|Volume 17, Issue 3|pp 726—739

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

Wei Yu Chua1, Lincoln Kai En Lim1, James Jia Dong Wang2, Aaron Shengting Mai1, Ling-Ling Chan3,5, Eng-King Tan4,5
  • 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • 2Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  • 3Department of Diagnostic Radiology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore, Singapore
  • 4Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore, Singapore
  • 5Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore
Received: September 19, 2024Accepted: January 9, 2025Published: March 17, 2025
https://doi.org/10.18632/aging.206222

Copyright: © 2024 Chua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.