Large Study Indicates Viagra Might Reduce Alzheimer's Risk

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In what is sure to create widespread skepticism — or enthusiasm, a study published in Nature Aging by researchers at Case Western Reserve, the Cleveland Clinic and the University of Indiana found that use of erectile dysfunction medication Viagra (sildenafil) was associated with a 69% lower incidence of Alzheimer’s disease.

It should be noted that the study does not say specifically that use of Viagra decreases the risk of Alzheimer’s disease. There is, at this time, no causal link. However, in an analysis of insurance claims data for 7.23 million people, use of Viagra was associated with a 69% reduced risk of Alzheimer’s disease.

The authors wrote, “We also found that sildenafil increases neurite growth and decreases phosphor-tau expression in neuron models derived from induced pluripotent stem cells from patients with AD, supporting mechanistically its potential beneficial effect in AD. The association between sildenafil use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial.”

Feixiong Cheng, a Cleveland Clinic researcher and lead author of the study, said, “Before this study, we didn’t expect we would identify sildenafil” as a drug candidate for Alzheimer’s disease.

Cheng and colleagues began by screening more than 1,600 drugs approved by the U.S. Food and Drug Administration (FDA) that are used to treat other diseases. In particular, they focused on drugs that target beta-amyloid and tau, two proteins that accumulate abnormally in the brains of Alzheimer’s patients.

They found several drugs that had the potential to affect protein accumulation, and Viagra was the best candidate. In their search of previous data, they found several studies in laboratory animals that showed sildenafil might help fight Alzheimer’s symptoms. In addition, they performed laboratory tests on human brain cells that demonstrated sildenafil’s ability to affect tau.

This led the team to analyze the database, looking at Alzheimer’s patients to determine if they were past or current users of sildenafil. Alzheimer’s patients who were on sildenafil were 69% less likely to develop Alzheimer’s than non-users over a period of six years. The drug was also associated with lower Alzheimer’s rates than drugs such as blood pressure medication losartan or blood sugar/diabetes drug metformin, which are currently being evaluated in clinical trials for Alzheimer’s.

The results open up possibilities, but it also raises a number of important questions. One is that, obviously, it’s primarily men who take Viagra. Any new studies would need to look at the effects in women as well. In some ways, erectile dysfunction is a type of blood pressure abnormality, so it’s possible the effect is related to blood pressure. Or they might be social components to the benefits if they’re eventually tied directly to use of the drug.

Viagra was originally developed as a heart drug. Its primary mechanism of action is to improve blood flow by widening blood vessels. The drug is also used in both men and women for a lung disease called pulmonary hypertension. There have also been studies of the drug in vascular dementia, the second most common type of dementia after Alzheimer’s. This form occurs from reduced blood flow to the brain.

Cheng is in the process of planning a Phase II trial to test the drug in early Alzheimer’s patients. Because the drug’s safety profile is well known, there is no reason for a Phase I study.

Cheng doubts that Viagra would be prescribed on its own for Alzheimer’s prevention.

“As Alzheimer’s is a complex disease caused by many factors, multi-target drugs or combination therapy targeting multiple disease pathways may offer better clinical benefits,” he said.

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