Researchers have uncovered that medications typically used for treating erectile dysfunction (ED) may offer an unexpected benefit: a reduced risk of developing Alzheimer’s disease. According to the findings published in Neurology, men who were prescribed ED drugs were found to be 18% less likely to be diagnosed with Alzheimer’s disease in subsequent years.
Alzheimer’s disease represents a significant challenge to global health, accounting for the majority of dementia cases and serving as a major cause of death. With the global prevalence of all-cause dementia set to triple by 2050, the race is on to find effective treatments and preventive measures.
While recent advancements have seen the development of monoclonal antibodies targeting the immune system to clear β-amyloid plaques in the early stages of Alzheimer’s, these treatments are not cures. The exploration of preventive interventions remains a critical research priority for promoting healthy aging and mitigating the burden of this disease.
“Although we’re making progress with the new treatments for Alzheimer’s disease that work to clear amyloid plaques in the brain for people with early stages of the disease, we desperately need treatments that can prevent or delay the development of Alzheimer’s disease,” said lead author Ruth Brauer, lecturer at University College London.
In this context, the repurposing of existing drugs for new therapeutic uses emerges as a cost-effective strategy for identifying potential treatments. Phosphodiesterase type 5 inhibitors (PDE5Is), widely recognized for their effectiveness in treating ED, have been explored for their neuroprotective benefits in previous animal studies.
These drugs, including sildenafil (Viagra), initially developed for hypertension and angina, have shown promise in improving cerebral blood flow and cognition, suggesting potential for repurposing in neurologic diseases like Alzheimer’s.
“Developing drugs for diseases like Alzheimer’s is a costly process and can take many years. Being able to repurpose drugs already licensed for other health conditions could help accelerate progress and open up new avenues to prevent or treat dementia-causing diseases,” said Leah Mursaleen, the head of research at Alzheimer’s Research in the United Kingdom, in an interview with the Science Media Centre.
Leveraging data from the IQVIA Medical Research Data (IMRD) database, which includes health records of over 16 million patients in the United Kingdom, the researchers embarked on a large population-based cohort study. The study focused on men aged 40 years and older who were newly diagnosed with ED between January 1, 2000, and March 31, 2017. The researchers excluded any participants with previous dementia diagnoses, cognitive impairments, or conditions that would contraindicate the use of PDE5I.
The study compared men who were prescribed PDE5Is (sildenafil, tadalafil, vardenafil, and avanafil) with those who did not receive such prescriptions, employing a detailed adjustment for various covariates including lifestyle factors, comorbidities, and other medications that could influence Alzheimer’s risk.
Over the course of the study, which followed participants for a median of 5.1 years, the team observed a lower incidence of Alzheimer’s disease among men who had been prescribed PDE5Is compared to those who had not. Specifically, the adjusted hazard ratio indicated an 18% reduction in the risk of developing Alzheimer’s disease for PDE5I users. This association was even more pronounced in individuals who had a greater number of PDE5I prescriptions, suggesting a potential dose-response relationship.
While these findings are promising, the researchers caution against overinterpretation due to several limitations. The reliance on prescription records does not guarantee medication adherence, and the diagnosis of Alzheimer’s was based on clinical read codes without confirmation through brain imaging or autopsy. Moreover, the study’s observational nature cannot establish causality, and there remains a possibility of unmeasured confounding factors that could influence the results.
“While we cannot say based on our findings whether the drugs themselves were reducing people’s risk of Alzheimer’s disease, the results are encouraging and may point to a new way to reduce Alzheimer’s risk,” said first author Matthew Adesuyan.
Future research should focus on understanding the mechanisms through which PDE5Is may confer neuroprotection and exploring the optimal duration and dosage for protective effects against Alzheimer’s. The researchers also highlight the need for randomized controlled trials to confirm these findings in a broader population, including women and individuals without cognitive impairments, to fully ascertain the therapeutic potential of PDE5Is in preventing Alzheimer’s disease.
“The role of nitric oxide neurotransmission in the consolidation, encoding and retrieval of memory has been known for a few years,” Francesco Tamagnini, a neurophysiologist at the University of Reading who was not involved in the study, told the Science Media Centre. “Nitric oxide is both involved peripherally on erectile function (by mediating vasodilation) and centrally in cognition, by modulating neuronal function. For example, nitric oxide dependent transmission has been observed as needed for perirhinal cortex-dependent visual recognition memory (Tamagnini et al., 2013).”
“In theory it is possible that promoting nitrergic transmission could improve memory function, but the question remains whether the observed association is describing a direct effect. This is a great study but more hard evidence is needed to test a mechanism of action. It could be that it exerts a therapeutic effect directly affecting neurons (if the drug is able to cross the blood brain barrier) and/or by increasing blood flow but both these hypotheses need to be tested.”
The study, “Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study,” was authored by Matthew Adesuyan, Yogini H. Jani, Dana Alsugeir, Robert Howard, Chengsheng Ju, Li Wei, and Ruth Brauer.
