The only word missing from this article is the word “throbbing” (but I digress).  It is an important study.

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Usage of the medication sildenafil – better known to most as the brand-name drug Viagra – is associated with dramatically reduced incidence of Alzheimer’s disease, new research suggests.

According to a study led by researchers at the Cleveland Clinic, taking sildenafil is tied to a nearly 70 percent lower risk of developing Alzheimer’s compared to non-users.

That’s based on an analysis of health insurance claim data from over 7.2 million people, in which records showed that claimants who took the medication were much less likely to develop Alzheimer’s over the next six years of follow up, compared to matched control patients who didn’t use sildenafil.

It’s important to note that observed associations like this – even on a huge scale – are not the same as proof of a causative effect. For example, it’s possible that the people in the cohort who took sildenafil might have something else to thank for their improved chances of not developing Alzheimer’s.

Nonetheless, the researchers say the correlation shown here – in addition to other indicators in the study – is enough to identify sildenafil as a promising candidate drug for Alzheimer’s disease, the viability of which can be explored in future randomized clinical trials designed to test whether causality does indeed exist.

“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,” explains computational biologist and senior author of the study, Feixiong Cheng from the Cleveland Clinic.

It’s not the first time sildenafil use has been linked with better health outcomes, with the drug previously showing promise in a range of different scientific contexts, including cancer and malaria research among others.

Here, Cheng’s team began by building over a dozen endophenotype modules, using computational techniques to map genetic factors that could hypothetically govern the manifestation of Alzheimer’s disease.

With 13 of these modules in hand, the researchers then looked at what kinds of FDA-approved drugs might hypothetically help against the identified phenotypes.

Out of over 1,600 such medications already approved by the FDA, sildenafil turned out to be one of the most promising candidates.

That might sound baffling – given the drug is so far used in the main only for treating erectile dysfunction and pulmonary hypertension – in the research community, there were already signs the sildenafil compound might have other kinds of health benefits, given its interactions with the amyloid and tau proteins implicated in Alzheimer’s pathology.

“Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself,” Cheng says.

“We hypothesized that drugs targeting the molecular network intersection of amyloid and tau endophenotypes should have the greatest potential for success… Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate.”

The hypothesis appears to be borne out by the health insurance data, with the team finding sildenafil users had a 69 percent reduced risk of Alzheimer’s disease compared to non-users – a reduction that was notably stronger than other kinds of medications also investigated in the study, including losartan, metformin, diltiazem, and glimepiride.

Of course, the researchers emphasize that none of this establishes causality, but on that front there may be other promising leads.

In separate experiments studying human brain cells in vitro to explore how sildenafil might confer protection against Alzheimer’s cognitive decline, the researchers observed that neurons treated with the drug showed elevated growth and reduced tau accumulation.

It’s early days, but those effects could well have something to do with the reduced chances of developing Alzheimer’s in the insurance cohort. To that end, it’s important to follow these leads further, the team says.

“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 says.

“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.”

The findings are reported in Nature Aging.