Could Viagra Help Prevent Alzheimer’s Disease?

It’s not unusual for scientists to look for new uses for drugs that are already on the market for other conditions. A case in point: Various researchers have been investigating whether a drug commonly prescribed to treat erectile dysfunction could help prevent and treat Alzheimer’s disease. 

The results have been a bit of a roller coaster as ongoing research has emerged. Evidence suggests the drug may be working by improving blood flow in the brain and possibly other ways as well.

The evidence builds 

First, a study led by experts at Cleveland Clinic found that taking sildenafil (brand name Viagra) could dramatically reduce a person’s risk of developing Alzheimer’s disease, though the authors said more research is needed. Sildenafil, approved by the U.S. Food and Drug Administration (FDA) in 1998, is also used to help people with pulmonary hypertension exercise more comfortably.

In the study, published in a 2021 issue of the journal Nature Aging, researchers analyzed health insurance claims from more than 7 million people and found that those who used sildenafil were 69 percent less likely to develop Alzheimer’s disease after six years of follow-up, compared with nonusers. Interestingly, the study found that use of sildenafil reduced the likelihood of Alzheimer’s in people with coronary artery disease, hypertension and type 2 diabetes — all of which are associated with an increased risk of Alzheimer’s — as well as in those without these high-risk medical conditions.

Using a complex network of methodologies, the study team screened a database of 1,608 FDA-approved drugs for medications that could be effective preventive agents or treatments for Alzheimer’s, based on their ability to interact with key proteins that play a role in creating the amyloid plaques and tau tangles that are hallmarks of the disease. Sildenafil emerged as a leader. Other medications that were investigated in the study include diltiazem and losartan (both used to treat hypertension) and glimepiride and metformin (both used to treat diabetes). In a head-to-head comparison with users of these drugs, people who took sildenafil were found to have a 55 to 65 percent lower risk of developing Alzheimer’s.

Study coauthor Feixiong Cheng, a researcher in Cleveland Clinic’s Genomic Medicine Institute, cautions that the findings highlight an association and do not prove a causal connection.

But then a study published in a 2022 issue of the journal Brain Communications — part of the National Institutes of Health’s Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study — contradicted those promising findings. The study used data from two groups of Medicare beneficiaries with pulmonary arterial hypertension. Nearly 10,000 people were being treated with a class of drugs called phosphodiesterase-5 inhibitors, including sildenafil and tadalafil (Cialis), and a comparative group of just over 3,000 people were taking other drugs to treat their hypertension. The researchers found that neither sildenafil nor tadalafil reduced the risk of Alzheimer’s and related dementias over time.

In 2023, the pendulum swung the other way again: In a study presented at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics, a team of researchers, which included Cheng, found that use of sildenafil was associated with a reduced likelihood of developing Alzheimer’s disease, compared to four other antihypertensive drugs, among nearly 19 million older adults over time. And in a study published in a 2023 issue of PLoS One, researchers evaluated an association between use of sildenafil and tadalafil and Alzheimer’s, based on medical records for more than 1.4 million patients in an Arkansas health system. They found that both men and women 65 and older who took these drugs for pulmonary hypertension were less likely to have developed Alzheimer’s.

The latest research, published Feb. 7, 2024, in the journal Neurology, found that men who took sildenafil and other medications like it for erectile dysfunction were 18 percent less likely to develop Alzheimer’s disease than people who did not take the drugs. The association was strongest among men who were issued the most prescriptions over the five-year study period.  

Study author Ruth Brauer, of the University College London, said in a news release that the results are “encouraging” but that they “warrant further research,” including a randomized controlled trial.

“These observational studies are very speculative, but I think they’re interesting in terms of exploring new options and potential treatments for Alzheimer’s disease,” says Ronald Petersen, M.D., director of the Mayo Clinic Alzheimer’s Disease Research Center, who was not involved in the studies. “It’s an example of how people are thinking more expansively about potential treatments for Alzheimer’s disease,” he added, referring to the drug repurposing strategy. “What we need is a randomized clinical trial on this.”