Phosphodiesterase 5 (PDE5) inhibitors (eg, sildenafil, tadalafil) do not appear to reduce the risk of Alzheimer disease and related dementias, according to a National Institutes of Health (NIH) study.

The aim of the DREAM (Drug Repurposing for Effective Alzheimer Medicines) study was to evaluate the risk of dementia/Alzheimer disease onset in patients treated with drugs that target specific metabolic pathways compared with those treated with alternative drugs for the same indication. By identifying existing medications that may be repurposed for dementia, clinicians may be able to provide faster treatment for those in need.

In a subset of the DREAM study, researchers from the NIH’s National Institute of Aging tested PDE5 inhibitors vs endothelin receptor antagonists (eg, bosentan, ambrisentan, macitentan) (ClinicalTrials.gov Identifier: NCT05039086). The primary outcome measure was the time to dementia onset among 12,947 Medicare beneficiaries being treated for pulmonary arterial hypertension.

“Across 4 separate analytic approaches designed to address specific types of biases including informative censoring, reverse causality, and outcome misclassification, we observed no evidence for a reduced risk of Alzheimer disease and related dementia with phosphodiesterase-5 inhibitors with hazard ratio [95% CI] of 0.99 [0.69-1.43], 1.00 [0.71-1.42], 0.67 [0.43-1.06], and 1.15 [0.57-2.34],” the authors stated.

Additionally, there was no evidence found that PDE5 inhibitors corrected molecular abnormalities associated with Alzheimer disease.

“These results do not provide support to the hypothesis that phosphodiesterase-5 inhibitors are promising repurposing candidates for Alzheimer disease and related dementia,” the authors concluded.

Previous findings from the DREAM study showed that certain drugs used for the treatment of rheumatoid arthritis appeared to lower the incidence of Alzheimer disease and related dementias in patients with cardiovascular disease.  In these patients, a lower risk was observed with tumor necrosis factor (TNF) inhibitors compared with abatacept. The overall findings, however, demonstrated no differences in the risk of dementia/Alzheimer disease onset in patients treated with tofacitinib, tocilizumab, or TNF inhibitors vs abatacept.

References

  1. NIH DREAM study finds Viagra and Cialis do not reduce risk of Alzheimer’s and related dementias. News release. October 4, 2022. https://www.nih.gov/news-events/news-releases/nih-dream-study-finds-viagra-cialis-do-not-reduce-risk-alzheimer-s-related-dementias
  2. Desai RJ, Mahesri M, et al. No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer’s disease and related dementia: results from the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study. Brain Communications. Published online October 4, 2022. doi.org/10.1093/braincomms/fcac247
  3. Desai RJ, Varma VR, et al. Comparative risk of Alzheimer disease and related dementia among Medicare beneficiaries with rheumatoid arthritis treated with targeted disease-modifying antirheumatic agents. JAMA Network Open. Published online April 8, 2022. doi:10.1001/jamanetworkopen.2022.6567