Study Explores Validity of Repurposed Erectile Dysfunction Drugs in Reducing Risk of Alzheimer Disease

Image Credit: Adobe Stock Images/Zerbor.com

All-cause dementia is growing in prominence across the globe, being estimated to impact 57 million people worldwide, which is predicted to balloon to 157 million by the year 2050. In the United Kingdom alone, Alzheimer's disease (AD) accounts for approximately 50%-75% of all dementia cases, making it the top cause of death.

Although there is currently no cure for AD, researchers continue to explore repurposing drugs in order to provide additional therapeutic options. For instance, phosphodiesterase type 5 inhibitors (PDE5Is)—which are often used to treat angina and hypertension—were found to cause smooth muscle relaxation in the corpus cavernosum due to its vasodilatory effects. Evidence in humans remains inconclusive (there has been promise in the conducted animal studies), but at the very least, this determination made sildenafil (also known as Viagra) an effectively repurposed treatment option for erectile dysfunction (ED).

Via a cohort study published in Neurology,¹ investigators sought to explore the association between drugs used to treat ED and a reduced risk of AD. It’s important to note that the study was not intended to prove that ED drugs actually lower AD risk.

With the help of electronic health records from IQVIA medical research data, the authors found269,725 men aged ≥40 years who had a new diagnosis of ED between 2000 and 2017. Those with cognitive impairment, confusion, or previous diagnosis of dementia were excluded from the study.

A total of 1,119 participants developed AD during the course of the study, and the results varied depending on whether they took the PDE5Is (the ED medication) or not, as 55% of the individuals had a prescription and 45% did not.

• For those who took PDE5Is, 749 of them developed AD, representing a rate of 8.1 cases per every 10,000 person-years at risk (PYAR, and a 95% CI 7.5–8.7).
• For those who did not take PDE5Is, the remaining 370 developed AD, representing a rate of 9.7 cases per every 10,000 person-years at risk (PYAR, and a 95% CI 8.7–10.7).

However, this cohort analysis presented various limitations, including the fact that PDE5I exposure was based on prescription records, which means that the investigators didn’t know whether patients actually collected or used the prescribed treatment. They also did not have any information from diagnostic brain imaging and autopsy to corroborate the accuracy of AD diagnosis that was pulled from clinical read codes. Further, they were unable to precisely evaluate a dose-response relationship due to the fact that the length of PDE5I treatment was not effectively recorded, since ED medication is not taken on a schedule per se, but on an as needed basis.

“The findings of this large population-based study suggest that the use of PDE5I may be associated with a reduced risk of incident AD,” the study authors concluded. “The greatest risk reduction was observed in those issued >20 prescriptions over a median follow-up of 5 years. This study warrants further investigation into the pathophysiologic action of PDE5I and neuroprotection. Further research is also needed to explore the optimal duration of the lag period, which is necessary to adequately address the prodromal phase of AD.

“To confirm the findings of our results in a wider population, a randomized controlled trial would be beneficial to evaluate the impact of PDE5I on AD. Such a study would include male and female participants, without cognitive impairment, randomized to receive a PDE5I in predefined doses or placebo. The primary outcomes would be the change in baseline cognitive function. This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Reference

1. Adesuyan M, Jani YH, Alsugeir D, Howard R, Ju C, Wei L, Brauer, R. Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease. Neurology. 2024;102(4). https://doi.org/10.1212/WNL.0000000000209131