Viagra May Significantly Cut Alzheimer’s Risk, Study Finds

An analysis of a large insurance-record database of more than seven million Americans has found that Viagra may reduce the risk of Alzheimer’s dementia by almost 70 percent.

In the study, published in the journal Nature Aging this month, a team of researchers from the Cleveland Clinic in Ohio relied on computational methodology to identify drugs approved by the U.S. Food and Drug Administration (FDA) that could be used as potential therapies for Alzheimer’s disease.

Scientists looked for medications that target amyloid plaques and tau tangles, which are believed to be responsible for the brain damage associated with Alzheimer's disease. Because the interplay between these two molecules is a greater contributor to Alzheimer’s than either amyloid or tau by itself, the investigators further narrowed their focus to pinpoint therapies that attack both.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” said the study team’s leader, Feixiong Cheng, PhD, of Cleveland Clinic’s Genomic Medicine Institute.

Per MedlinePlus, the drug is a common prescription medication, currently sold as Viagra to treat erectile dysfunction and as Revatio to improve the ability to exercise in adults with pulmonary arterial hypertension (high blood pressure in the vessels carrying blood to the lungs, causing shortness of breath, dizziness, and tiredness).

A systematic review published in April 2020 in the Journal of Alzheimer's Disease Reports looked at research evaluating sildenafil in relation to Alzheimer’s and found the medication to be linked with increased neurogenesis (growth and development of nerve tissue) and decreased inflammation.

This type of benefit makes sense, according Len Horovitz, MD, an internist and pulmonary specialist with Lenox Hill Hospital in New York City, because sildenafil improves blood flow.

“Most neurologists will tell you that one of the most important things in Alzheimer's is exercise, because exercise increases blood flow,” says Dr. Horovitz, who was not involved in the study. “Anything that increases blood flow will have a beneficial effect on brain function. It wouldn't surprise me if this is going to be a promising treatment — although whether it offers prevention, it’s hard to say.”

Results from this study suggested that prevention might indeed be an outcome. In their analysis of insurance claims data for 7.23 million individuals, Cheng and his collaborators found that sildenafil users were 69 percent less likely to develop Alzheimer’s disease than non-sildenafil users after six years of follow-up.

In looking at sildenafil in relation to other meds being explored as potential Alzheimer’s treatments, the study authors discovered that Viagra/Revatio provided a 55 percent reduced risk of the disease compared with losartan, 63 percent compared with metformin, 65 percent compared with diltiazem, and 64 percent compared with glimepiride.

Dr. Cheng highlighted that sildenafil reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension, and type 2 diabetes (all of which are comorbidities significantly associated with risk of dementia) as well as in those without those conditions.

While the study established a link between the drug and preventing Alzheimer’s, the authors stressed that this investigation did not prove that sildenafil actually offers protection or benefit in this regard.

In separate research examining brain cells from Alzheimer’s patients, Cheng and his collaborators found that sildenafil increased brain cell growth and decreased hyperphosphorylation of tau proteins (a process that leads to neurofibrillary tangles). These results gave scientists some biological insights into how the drug may protect the brain.

As many as 5.8 million Americans are living with Alzheimer's disease, and the number of people older than 65 with the disease doubles every five years, according to the Centers for Disease Control and Prevention (CDC). While the Alzheimer’s Association lists treatments that may slow disease progression, no cure exists.

“More than ever before, Alzheimer’s researchers understand that a variety of approaches will be needed — most likely used in combination — for effective treatment of the disease,” says Claire Sexton, DPhil, the director of scientific programs and outreach for the Alzheimer's Association. “Scientists are more extensively testing the potential benefits of drugs approved for other diseases for the treatment of dementia. Repurposing existing drugs for new uses can speed up the research process … and review by the U.S. Food and Drug Administration.”

Dr. Sexton also points out an advantage with repurposed drugs: Their potential side effects are already known.

As a next step in their research, Cheng and his colleagues are planning a randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients.