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Researchers identified sildenafil, commonly known as Viagra, as a promising drug candidate to help prevent and treat Alzheimer’s disease, according to a study led by the Cleveland Clinic.  

"We found that sildenafil usage was significantly associated with a 69% reduced risk" of Alzheimer’s, the researchers stated in the report published in the journal Nature Aging.  

Sildenafil is an FDA-approved drug used to treat erectile dysfunction known under the name Viagra and pulmonary hypertension under the name Ravatio. 

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The researchers examined over 1,600 FDA-approved drugs to see which had the potential to be repurposed to treat Alzheimer’s disease effectively. The Cleveland group stated in a release that the interplay between two proteins, amyloid and tau, contributed more significantly to Alzheimer’s than either protein by itself.  

"Therefore, we hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success," Dr. Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medicine Institute, said in a news release. 

Cheng, who led the study, added, "Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate". 

Viagra was associated with a 69% reduced risk of Alzheimer’s, the study found.

Viagra was associated with a 69% reduced risk of Alzheimer’s, the study found. (BSIP/Universal Images Group via Getty Images, File)

The Cleveland researchers examined the relationship between sildenafil and outcomes in patients with Alzheimer’s disease by performing a large-scale analysis of pharmacy claims through a database of over 7 million patients over a period of six years, according to the report.  

The investigators compared patients who took sildenafil with those who did not.  The analysis also included patients using comparator drugs that were currently in an active Alzheimer’s clinical trial such as the antihypertensive drug losartan and anti-diabetic drug metformin, and also drugs that were not yet reported as relevant to Alzheimer’s disease, such as the antihypertensive drug diltiazem and the type 2 diabetes drug glimepiride, according to the release.  

In a 6-year follow-up, patients who took sildenafil were 69% less likely to develop Alzheimer’s disease than those who did not take the drug, according to the published report.  

Researchers followed up with patients years after they took the drug.

Researchers followed up with patients years after they took the drug. (BSIP/Universal Images Group via Getty Images, File)

The study authors also found that those who took sildenafil had a 55% reduced risk of Alzheimer’s compared to those who took losartan, 63% less risk compared to those who took metformin, and 65 reduced risk of developing Alzheimer’s when compared to patients who took diltiazem. The sildenafil users also had a 64% less risk of Alzheimer’s compared to the group who took glimepiride. 

"Notably, we found that sildenafil use 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 the disease, as well as in those without," Cheng said in a news release.  

The researchers furthered the study on the effects of sildenafil on Alzheimer’s by developing a model of an Alzheimer’s patient-derived brain cell using stem cells, according to the study. The investigators found that sildenafil increased brain cell growth among other effects, according to the release. 

The next step is a series of trials to confirm cause and effect.

The next step is a series of trials to confirm cause and effect. (BSIP/Universal Images Group via Getty Images, File)

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"Because our findings only establish an association between sildenafil use and reduced incidence of Alzheimer’s disease, we are now planning a mechanistic trial and a phase II randomized clinical trial to test causality and confirm sildenafil’s clinical benefits for Alzheimer’s patients," Cheng said in the statement.  

According to the release, the researchers predict their approach will be applied to help accelerate the drug discovery process in other degenerative neurological diseases such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.