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A new study of nearly 270,000 men suggests a pharmaceutical commonly used for erectile dysfunction sold commercially under brand names like Viagra may lower the risk of Alzheimer's disease by some 18 percent.
But more research in the form of clinical trials is needed to understand optimal dosage, treatment time, and whether the slight protective effect extends to women.
"We desperately need treatments that can prevent or delay the development of Alzheimer's disease," says study author Ruth Brauer, a pharmacoepidemiologist at the University College London.
"These results are encouraging and warrant further research."
With the burden of Alzheimer's disease growing in aging populations, and only a slow trickle of modestly effective therapies making their way through approvals, researchers have turned their attention to existing drugs to see if any could serendipitously slow cognitive decline.
For instance, last year a team of researchers from the University of Kentucky found that a treatment approved for multiple sclerosis also encouraged brain cells called microglia to mop up toxic proteins associated with Alzheimer's disease in mice.
At the same time, scientists are still trying to refine their understanding of what causes Alzheimer's disease, with new culprits emerging in addition to amyloid-beta plaques and tau tangles – the two molecular hallmarks of the disease.
Extremely rare cases of people harboring a lucky combination of genetic mutations that protect them from Alzheimer's disease have also revealed new ways of possibly slowing the disease.
But the fact remains that in the US alone, 6.7 million people aged 65 and older are living with Alzheimer's, a number which could more than double by 2060 unless we find some way to intervene.
There has been some back and forth over the past few years about whether commonly used erectile dysfunction drugs known as phosphodiesterase type 5 (PDE5) inhibitors (such as sildenafil, which is sold under the brand name Viagra and also used to treat high blood pressure) could reduce the risk of people developing Alzheimer's disease.
A 2021 observational study found evidence that taking sildenafil lowered the odds of an Alzheimer's diagnosis among Americans by almost 70 percent, but then a shorter, smaller 2022 study found no such effect when following patients for less than 2 years.
Evidence from a 2023 study swung the needle back the other way, but all in all the findings from these observational studies – which cannot disentangle cause and effect – have been inconclusive.
In this new study, again observational, prescriptions issued to almost 270,000 men aged 40 years and older newly diagnosed with erectile dysfunction were analyzed using electronic health records from the UK.
While these records don't show whether or not people filled their prescriptions or took the medications, they indicate who was using which drugs, and how often.
About half were prescribed sildenafil or a similar erectile dysfunction medication from the same drug class of PDE5 inhibitors, and 1,119 men went on to develop Alzheimer's disease.
Those prescribed a PDE5 inhibitor were 18 percent less likely to develop Alzheimer's disease than non-users, and the risk was lower again if people received more than 20 prescriptions over an average of 5 years.
However, when patients were grouped by the drug they were prescribed, only sildenafil but not tadalafil or vardenafil was associated with a reduced risk.
Also, the apparent protective effect almost evaporated when the researchers excluded patients who had less than 3 years of follow-up, to account for the possible overlap between someone starting an erectile dysfunction medication and the onset of Alzheimer's, which can occur years before diagnosis.
"More research is needed to confirm these findings, learn more about the potential benefits and mechanisms of these drugs and look into the optimal dosage," Brauer says.
"A randomized, controlled trial with both male and female participants is warranted to determine whether these findings would apply to women as well."
The study has been published in Neurology.
