After a decades-long and largely fruitless hunt for drugs to combat Alzheimer’s disease, an unlikely candidate has raised its head: the erectile dysfunction pill Viagra.
Researchers found that men who were prescribed Viagra and similar medications were 18% less likely to develop the most common form of dementia years later than those who went without the drugs.
The effect was strongest in men with the most prescriptions, with scientists finding a 44% lower risk of Alzheimer’s in those who received 21 to 50 prescriptions of the erectile dysfunction pills over the course of their study.
While the findings are striking, the observational study cannot determine whether Viagra and similar pills protect against Alzheimer’s or whether men who are already less prone to the condition are simply more likely to use the tablets.
“We can’t say that the drugs are responsible, but this does give us food for thought on how we move into the future,” said the lead author Dr Ruth Brauer at University College London. “We now need a proper clinical trial to look at the effects of these drugs on Alzheimer’s in women as well as men.”
Brauer and her colleagues analysed medical records for more than 260,000 men who were diagnosed with erectile dysfunction but had no evidence of memory or thinking problems.
Just over half were taking PDE5 inhibitor drugs, including sildenafil (sold as Viagra), avanafil, vardenafil and tadalafil. The men were followed for an average of five years to record any new cases of Alzheimer’s.
An estimated 55 million people live with dementia around the world, most of which is due to Alzheimer’s. New drugs that clear aberrant proteins from the brain have shown promise for slowing down the disease, but the effects of the medicines appear marginal.
Viagra was originally developed to treat angina and high blood pressure, but when Welsh miners who took part in a trial in Merthyr Tydfil remarked on its unexpected night-time side-effects, the drug became a multibillion dollar erectile dysfunction pill.
PDE5 inhibitors work by relaxing veins and arteries, allowing blood to flow more freely. Studies in animals show that this improves blood flow in the brain, which may help protect against Alzheimer’s. Further work has shown that PDE5 inhibitors raise levels of a compound called cGMP, which may also help to protect brain cells.
There are other possible explanations for the findings, published in the journal Neurology.
Because the information is not recorded reliably in medical records, the researchers were unable to account for differing levels of physical and sexual activity among the men. It may be that the most physically and sexually active men, who had a low risk of developing Alzheimer’s, were most likely to use Viagra or similar pills.
Previous studies into Viagra and Alzheimer’s have found contradictory effects. In 2021, researchers at the Cleveland Clinic in Ohio reported a 69% lower risk of Alzheimer’s among Viagra users, while a Harvard study in 2021 found no protective effect in patients with pulmonary hypertension.
If PDE5 inhibitors do protect against Alzheimer’s, the drugs would be expected to work in women as well as men. “We think it would be very worthwhile to run a trial in a wide group of people,” Brauer said.
“This is a significant development, as repurposing existing drugs for the prevention of dementia is a promising strategy to stop dementia from developing in the first place,” said Dr Ivan Koychev, a senior clinical researcher at the University of Oxford.
But he warned that it would be difficult to run a blinded placebo-controlled trial, where neither doctors nor patients know who receives which, given the prominent effects of the drugs.
Dr Leah Mursaleen, head of research at Alzheimer’s Research UK, said developing drugs for Alzheimer’s disease was costly and could take many years.
“Being able to repurpose drugs already licensed for other health conditions could help accelerate progress and open up new avenues to prevent or treat dementia-causing diseases,” she added.
Dr Madhav Thambisetty, a senior investigator at the US National Institute on Aging, whose 2021 study found no protective effect of Viagra, said there is always a risk of unmeasured factors, such as the quality of people’s sleep or how well they control their diabetes, producing false results.
He also questioned the plausibility of a drug like sildenafil, which is only used when needed in patients with erectile dysfunction, altering the course of a chronic, progressive neurodegenerative disease.
“While sildenafil is known to reach the brain from blood, can its levels in the brain be maintained at high enough concentrations over a sustained period of time that may be required to alter the trajectory of Alzheimer’s disease?” he said.
“This is an important question to consider for drugs like sildenafil that are only used ‘as needed’ in comparison to drugs that are used every day or multiple times a day over a prolonged period of time.”
