Could the next Alzheimer’s drug discovery be… Viagra?

Epidemiological studies can often throw out intriguing and sometimes erroneous correlations between a variable and a disease, but UK scientists say a finding that Alzheimer’s disease seems to be less common in Viagra users warrants further investigation.

Researchers from University College London (UCL) found that men prescribed erectile dysfunction (ED) drugs based on phosphodiesterase 5 inhibitors, including Viagra (sildenafil), were 18% less likely to develop Alzheimer’s in later life.

Their study – published in the journal Neurology – looked at prescription records from almost 270,000 men aged over 40 and with an average age of 59 who were newly diagnosed with ED, and revealed that five years later there were 8.1 cases of Alzheimer’s among those treated with PDE5 inhibitors and 9.7 cases in those who did not take them.

There was also some evidence of a dose response, with a stronger 44% reduction in men who had the most prescriptions, and the effect was most pronounced in men with cardiovascular risk factors like high blood pressure and diabetes.

The result is very preliminary, and might still be explained by some other factor; could men who seek to take control of ED be more likely to have an active lifestyle, for example? The researchers note, however, that PDE5 inhibitors have some properties that could point to a possible mechanism for the prevention of dementia.

PDE5 inhibitors raise levels of cyclic guanosine monophosphate (cGMP), a nucleotide secondary messenger that seems to be present in lower-than-usual levels in the brains of people with Alzheimer’s. Animal studies have also shown that drugs in the class have neuroprotective properties, improve cerebral blood flow, and reduce inflammation in the central nervous system.

One of the scientists behind the study, Dr Ruth Brauer, said that the hope is to run a prospective, placebo-controlled control trial in both men and women to see if the association is real. It’s not clear yet how that study might be designed to prevent subjects from knowing which group they were in, given the pronounced physical effects of ED drugs.

“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,” stressed Brauer.

Despite the emergence of drugs that treat Alzheimer’s by clearing amyloid plaques – like Eisai/Biogen’s Leqembi (lecanemab) – there is a desperate need for new treatments that can delay or prevent the development of the disease, she added.

It’s worth noting also that there have been contradictory findings in two smaller retrospective studies looking at Viagra use and Alzheimer’s, with one finding a 69% reduced risk and a second – focusing only on PAH patients – revealing no effect.

Prof Tara Spires-Jones, president of the UK Dementia Research Institute at the University of Edinburgh, said that the study was “well-conducted, and authors are appropriately cautious in their interpretation of the data.”

She added: “This study does not conclusively prove that erectile dysfunction drugs reduce Alzheimer’s risk but provide good evidence that this type of drug is worth further study in future.”

Initially developed for high blood pressure and angina, Viagra has already been repurposed to treat ED as well as pulmonary arterial hypertension. Could it find a new lease of life as a dementia treatment? Time – and plenty of clinical testing – may tell.