Past research has shown that men who take drugs for erectile dysfunction may also be helping to keep their hearts healthy. Now, new studies are linking the drugs to brain health, too. The studies excited both the medical community and the public at large, as there is currently no approved medication to prevent forms of dementia such as Alzheimer’s disease.
A study published in December 2021 supported by the National Institute of Aging found that men who took sildenafil (Viagra) were significantly less likely to develop Alzheimer’s disease. Separate research published at the beginning of 2022 revealed that tadalafil (Cialis) may have the potential to increase blood flow in the white matter of the brain, which is related to vascular dementia.
Researchers currently believe that the onset of Alzheimer’s and other kinds of dementia is tied to a chronic lack of blood flow to the deep brain area.
Both Viagra and Cialis are phosphodiesterase-5 (PDE5) inhibitors, which help erectile dysfunction (ED) by increasing blood flow to the penis. Because these medications stimulate blood flow, some scientists have speculated that they could influence blood circulation in the brain and provide some protection against dementia as well.
But the most recent research has cast some doubt on whether this class of drugs is genuinely effective at lowering the risk of dementia. Results from a National Institutes of Health study in October 2022 indicated that sildenafil (Viagra) and tadalafil (Cialis) may not be suitable candidates for treating dementia.
Here, three dementia researchers explain how to understand the science: Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital; Feixiong Cheng, PhD, a researcher at Cleveland Clinic’s Lerner Research Institute; and Percy Griffin, PhD, director of scientific engagement with the Alzheimer’s Association.
Dr. Desai led the study that found no evidence that Viagra and Cialis reduced the risk of Alzheimer’s or related dementias, and Dr. Cheng led the study that found that Viagra was associated with a reduced risk of Alzheimer’s disease.
These responses have been lightly edited for length and clarity.
Q: How do you explain the conflicting results between these two studies?
Desai: The first study compared those who took Viagra for any reason to those who did not take it or took medications for other indications, including diabetes and hypertension. That design likely resulted in a comparison of individuals with erectile dysfunction (the most common indication for Viagra) to generally older individuals with diabetes or hypertension, both of which are risk factors for dementia.
It is plausible to hypothesize that older men who initiate Viagra for ED are likely to have some level of activity and overall better general health compared with those who do not. … One of the factors explaining lower risk of dementia with Viagra in the earlier study could be the characteristics of the patients who took the medication and not the medication itself.
In contrast, our study included only those with pulmonary arterial hypertension (PAH), which is also an indication for medications like Viagra and Cialis. We compared dementia incidence in those who took these drugs to the incidence among people who took a different medication to treat their PAH, which likely resulted in a comparison of more similar patients.
Cheng: There are several possible reasons to explain the conflicting results. The Desai study … was a much smaller group of people — as pulmonary hypertension is a rare disease with limited patient sample size.
Pulmonary hypertension has very poor outcomes, with about three years of survival based on published literature data. Yet Alzheimer’s disease is a chronic disease, with 15 to 20 years of development process. The authors of the later study cannot see prevention effects during this short follow-up time of about three years.
In addition, the dose of Viagra prescribed for pulmonary hypertension is much lower than the dose given for ED that we tested in our paper.
Q: Why are researchers interested in repurposing drugs like this for other therapeutic purposes?
Griffin: More than ever before, Alzheimer’s researchers understand that a variety of approaches will be needed — most likely used in combination, as we do in heart disease — for effective treatment of the disease.
Looking for possible additional therapeutic uses of drugs already available on the market, known as drug repurposing, is a strategy that is currently being used for drug discovery for Alzheimer’s and other dementias, and it has been successfully used in many other diseases.
Cheng: We don’t have U.S. Food and Drug Administration (FDA)–approved, highly effective … drugs for Alzheimer’s disease, and the failure rate of Alzheimer’s clinical trials is over 99 percent. Repurposable drugs have been approved by the FDA for other indications, with well-known safety profiles. Drug repurposing can significantly reduce the timeline and cost of drug development for Alzheimer’s disease and other challenging diseases if broadly applied.
Q: Should researchers keep looking into Viagra and Cialis for dementia prevention? What further study is needed?
Cheng: The clinical benefit of Viagra in Alzheimer’s disease must be further tested using other patient data or even future clinical trial studies. Our study and other published preclinical studies only showed that Viagra is a possible treatment for Alzheimer’s disease.
Desai: More research in diverse populations with larger samples of patients would be helpful but should be designed with sound principles to rule out as many alternative explanations as possible. The biology behind these drugs is certainly interesting — however, so far there has not been a convincing study involving human participants demonstrating the beneficial effect.
Griffin: It’s important to understand that these studies are simply association studies based on a review of health insurance claims data, and we have no clinical trial data demonstrating the effectiveness of Viagra as a treatment for Alzheimer's.
Q: What is the overall takeaway for people concerned about their dementia risk?
Griffin: Even though it’s not a clinical trial, research like this can be very valuable. It’s a first step in looking for possible clues that a known treatment may be appropriate for use in another disease. We’ve seen some other data that suggests Viagra treatment is associated with increased neurogenesis (brain cell generation) and decreased inflammation, but more research is needed. That said, it will be important to conduct rigorous clinical trials to determine both the safety and effectiveness of the treatment approach.
While you should absolutely be talking to your doctor about aging and cognition/memory, it would not be appropriate to ask your doctor for this drug as an Alzheimer’s treatment or prevention, as it has not been tested for this purpose. If you are taking this drug under doctor’s supervision, or have access to it, do not take it as an Alzheimer’s treatment or prevention.