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Can Viagra help reduce risk of Alzheimer's disease?

New York, Dec 7 : US researchers have found that impotence pill Viagra may help prevent as well as treat Alzheimer's disease.

Sildenafil, approved by the US Food and Drug Adminstration (FDA) for erectile dysfunction (Viagra), is associated with 69 per cent reduced incidence of Alzheimer's disease, according to the findings published in the journal Nature Aging.

A team from Cleveland Clinic analysed a database of more than 7 million patients, and used computational methodology to screen and validate over 1,600 FDA-approved drugs as potential therapies for Alzheimer's.

The buildup of beta amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles -- two hallmarks of Alzheimer's-related brain changes. The team pinpointed drugs that target both amyloid and tau as having higher scores compared to drugs that target just one or the other.

"Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate," said Feixiong Cheng, from Cleveland Clinic's Genomic Medicine Institute.

Further, the analysis included patients using comparator drugs that either were in an active Alzheimer's clinical trial (losartan or metformin) or were not yet reported as relevant to the disease (diltiazem or glimepiride).

They found that sildenafil users were 69 per cent less likely to develop Alzheimer's disease than non-sildenafil users after 6 years of follow-up. Specifically, sildenafil had a 55 per cent reduced risk of the disease compared to losartan, 63 per cent compared to metformin, 65 per cent compared to diltiazem and 64 per cent compared to 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.

The researchers also developed an Alzheimer's patient-derived brain cell model using stem cells.

In the model, they found that sildenafil increased brain cell growth and decreased hyperphosphorylation of tau proteins -- a hallmark which leads to neurofibrillary tangles --, offering biological insights into how sildenafil may influence disease-related brain changes.

"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 randomised clinical trial to test causality and confirm sildenafil's clinical benefits for Alzheimer's patients," said Cheng.

"We also foresee our approach being applied to other neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process."