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Could Viagra Help Prevent and Treat Alzheimer’s Disease?

Experts explore the drug’s potential impact on the most common form of dementia

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Scientists may have discovered a new use for a drug commonly prescribed to treat erectile dysfunction. A study led by experts at the Cleveland Clinic found that taking sildenafil (brand name Viagra) could dramatically reduce a person’s risk of developing Alzheimer’s disease, though more research is needed. Sildenafil, approved by the U.S. Food and Drug Administration (FDA) 23 years ago, is also used to help people with pulmonary hypertension exercise more comfortably.

In the study, published in the journal Nature Aging, researchers analyzed health insurance claims from over 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 to 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. 

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Discovering new uses for old drugs

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. Still, the results are promising and researchers are already planning to conduct a phase II randomized clinical trial to test the effects of the drug in people with early Alzheimer’s. 

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“I think it’s 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 study. “It’s a scholarly study with a very elegant analytical model — and an example of how people are thinking more expansively about potential treatments for Alzheimer’s disease,” he added, referring to the study’s drug repurposing strategy.

The concept — finding new therapeutic uses for already licensed drugs — is one that’s gaining ground in Alzheimer’s research after decades of drug-discovery disappointment. The reason? It offers a faster and more cost-effective approach, which is especially important as the number of Americans living with Alzheimer’s is expected to spike from over 6 million to nearly 14 million by 2050, barring any breakthroughs in treatment.

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So far, the FDA has approved a few medicines that help manage symptoms of Alzheimer’s disease but do not stop it from advancing. One treatment has received a green light from the agency for its potential to slow the progression of the disease, although it has yet to prove that it can alter the course of cognitive decline in a clinical setting, the National Institute on Aging says.  

A matrix of possible mechanisms 

How is it that Viagra may be able to stave off a neurodegenerative disease?

As part of the study, the researchers developed a brain cell model using stem cells from actual Alzheimer’s patients to explore how sildenafil might confer protection against Alzheimer’s-associated cognitive decline. They found that sildenafil increased neuron growth and reduced the accumulation of tau proteins, which form disruptive tangles in the brains of people with Alzheimer’s. The researchers noted that other studies have shown that drugs that are phosphodiesterase inhibitors, like sildenafil, have additional therapeutic effects in preclinical models of Alzheimer’s disease, such as decreasing the accumulation of amyloid plaques (another hallmark of Alzheimer’s), improving cognitive impairment and enhancing the level of brain-derived neurotrophic factor, a key molecule in memory function.  

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The current study found that the effects of sildenafil on reducing the risk of Alzheimer’s disease were particularly strong for men, which isn’t surprising given that the drug is prescribed primarily to men with erectile dysfunction. But Cheng told AARP he thinks Viagra has the potential to reduce the risk of Alzheimer’s disease in women as well, which would be especially beneficial given that approximately two-thirds of people who are diagnosed with Alzheimer’s are women.

“If the mechanisms are increased blood flow, which could enhance cognitive function, and other biochemical effects on amyloid and tau, [the drug] could be effective in women as well as men,” Petersen adds. “The mechanisms they’re suggesting are probably not sex-specific.”

Looking to the future

In addition to further studying sildenafil’s impact on Alzheimer’s, Cheng says his team is researching other drug combination therapies that could interrupt the disease through a variety of pathways, including reducing inflammation. He also foresees the approach “being applied to other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process,” Cheng said in a statement.

If the results of these studies prove to be positive, the arsenal of potential preventive therapies and treatments for Alzheimer’s may expand in ways that have important clinical implications.  

“Alzheimer’s is a complex disease,” Cheng says — one that likely requires a personalized approach “and drug combination therapy strategies” to prevent and treat it in the future.

Stacey Colino is an award-winning writer, specializing in health, psychology, and science. Her work has appeared in The Washington Post, U.S. News & World Report, Prevention, Newsweek, Parade, and many other national magazines.

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