Alzheimer’s disease affects millions of people around the world and is the leading cause of dementia for older adults. As Alzheimer’s researchers continue to search for effective treatment options, they have been investigating whether existing drugs might prevent Alzheimer’s disease from developing in the first place.

One of the drugs being researched is sildenafil (Viagra), the little blue pill used to treat erectile dysfunction and a lung disease called pulmonary hypertension. The role of Viagra and other erectile dysfunction drugs has been the topic of a lot of debate in the Alzheimer’s research community. What does the research say about this intriguing potential side effect of sildenafil? Let’s break down these mixed results.

The Relationship Between Viagra and Alzheimer’s

Why do scientists think there might be a link between Viagra and Alzheimer’s disease? There are some guesses based on how the medication works and what causes Alzheimer’s, but no clear link has been proved.

One theory is about how sildenafil affects blood flow. Sildenafil belongs to a class of drugs called phosphodiesterase type 5 inhibitors (PDE5 inhibitors). It dilates (widens) the blood vessels, allowing blood to travel to the penis to cause an erection and into the lungs of people with pulmonary hypertension to help them breathe more easily. This effect may have implications for brain health as well — increasing blood flow to the brain may reduce the buildup of the harmful amyloid plaques that appear in the brains of people with Alzheimer’s disease.

No study has yet proved this hypothesis in humans, although it has been observed in some laboratory studies of brain cells. Two major studies have tried to explore the relationship between sildenafil and Alzheimer’s risk on a population level, with extremely different results. Let’s dive into the scientific debate.

Support for a Connection Between Viagra and Alzheimer’s

In 2021, scientists from Cleveland Clinic published a controversial paper in Nature Aging stating that people who take sildenafil have a 69 percent lower risk of developing Alzheimer’s disease than people who take other common drugs to treat high blood pressure and diabetes. These results sound significant, but readers should take this study with a grain of salt.

Study Population

This study got its data by reviewing the health insurance claims data for 7.23 million people. Even though this is an extremely large sample size, the way the data was collected was purely observational and looked back in time. Therefore, the researchers couldn’t state that sildenafil prevents Alzheimer’s. That’s because there are other factors that may create a false relationship between sildenafil and Alzheimer’s, even after they controlled the findings for age, sex, race, and other diseases.

Laboratory Findings

To try to discover more information, the same scientists conducted an additional step to their research, this time in the lab setting. They found that in studies of the brain cells of people with Alzheimer’s, sildenafil increases the growth of neurites, while decreasing the tau protein that is associated with Alzheimer’s. These signs point to a potential benefit of sildenafil on the brain, in relation to risk of developing Alzheimer’s.

However, because this study took place on cells instead of humans, the evidence is not strong enough to change how sildenafil should be prescribed or used.

How Valid Is This Study?

One study alone is not enough to prove a relationship. Even the study authors stated that clinical trials are the next step to establish this potential connection.

However, since its publication, the authors have had to defend their study design choices with updates to their original paper in 2023, after their study methods were questioned in a 2023 Letter to the Editor. Since the original study was conducted, conflicting new research has emerged that has continued this debate in the academic world.

Evidence Against a Connection

In 2022, the results from another major new study called DREAM (Drug Repurposing for Effective Alzheimer’s Medicines) was published on the topic of Alzheimer’s risk when taking sildenafil or tadalafil (sold under the brand name Cialis). This study, which looked at data on more than 13,000 people, found no connection between developing Alzheimer’s and taking either of these PDE5 inhibitors.

This paper, published in Brain Communications by a group of scientists at the National Institutes of Health (NIH), reported no significant difference in Alzheimer’s risk between people who took sildenafil or tadalafil and people who didn’t. How did this study, conducted in such a similar way, find such different results than the first Nature Aging article?

Study Design

The NIH study followed a similar design to the previous study but got its data from a different location. This research looked at all Medicare claims, as well as cell-cultured laboratory research. Everyone in the study population had a condition called pulmonary arterial hypertension (PAH), because sildenafil and tadalafil are regularly used to treat people with this lung disease.

This study compared two groups:

• Group 1 had taken sildenafil or tadalafil for their PAH.
• Group 2 took another drug used to treat PAH, belonging to a class called endothelin receptor antagonists.

Researchers looked to see who in either group developed Alzheimer’s disease or other dementias. In their analysis, the authors controlled for 76 confounders — qualities about the study participants that could influence the outcome, such as age and race. This was done to prevent bias in the study results.

The researchers used four different data analysis techniques, because the way that data is analyzed may bias the results. In each one of their analyses, they found no reason to believe that sildenafil or tadalafil reduced the risk for Alzheimer’s disease. These results were confirmed by their laboratory study, which showed no changes to brain cells of those who took these drugs.

How Valid Is This Study?

This study was very high quality, with many techniques in the study design and data analysis that made the results quite believable. While it was conducted in a very specific population — people with PAH — the complete lack of association between sildenafil and Alzheimer’s in this study should be taken seriously.

The Bottom Line

While the idea that sildenafil or other PDE5 inhibitors could reduce the risk of Alzheimer’s or other forms of dementia may seem fascinating, it remains a topic of ongoing research and scientific debate. Sildenafil is not approved by the U.S. Food and Drug Administration (FDA) to prevent or treat Alzheimer’s disease. The evidence is not currently strong enough for doctors to prescribe PDE5 inhibitors to reduce the risk for Alzheimer’s disease.

While the initial study raised interesting possibilities, many more high-quality, randomized studies would need to show an association before doctors change how they prevent and treat Alzheimer’s. One study cannot be taken as the truth, and right now, there is no consensus in the scientific community about this subject.

If you’re concerned about your risk for developing Alzheimer’s, due to a strong family history or genetic testing, there are many strategies to support brain health that have been supported by science. Some ways to reduce your risk of Alzheimer’s disease and related dementias include:

• Living a healthy lifestyle
• Exercising regularly
• Quitting smoking
• Consuming a balanced diet
• Staying active, mentally and socially

Make sure to take good care of any other illnesses you are living with, especially heart disease. Check in with a health care provider regularly. If you have any questions about medications you are taking, ask your doctor.

Talk With Others Who Understand

On myALZteam, the social network for caregivers of people with Alzheimer’s disease, more than 85,000 members come together to ask questions, give advice, and share their stories with others who understand life with Alzheimer’s.

Do you have concern about yourself or a loved one developing Alzheimer’s disease? What do you think about this Viagra debate? Share your experience in the comments below, or start a conversation by posting on your Activities page.