Phosphodiesterase type 5 inhibitors such as Viagra are, of course, best known for effectively treating erectile dysfunction, but a study of nearly 270,000 men has added to the growing body of evidence that they may also lower the risk of developing Alzheimer's disease.
University College London (UCL) researchers looked at 269,725 male participants in the UK, with an average age of 59, with no evidence of cognitive impairment, who had recently been diagnosed with erectile dysfunction. In the five-year study, the researchers assessed the cohort in two groups: those who had prescriptions for erectile dysfunction drugs such as sildenafil (Viagra) (55% of participants), and those who did not have their erectile dysfunction treated in this way (45%).
What they found was that of the 1,119 participants who developed Alzheimer’s disease, 749 were taking erectile dysfunction drugs, while 370 were not. But when measured by person-years (the number of people in the study and the amount of time each person spent in the study), the researchers found that Alzheimer's prevalence in those on medication was 8.1 cases per 10,000 person-years, compared to 9.7 cases per 10,000 person-years for those not taking erectile dysfunction drugs.
And when other factors were accounted for – age and lifestyle such as smoking and alcohol consumption – the researchers found that those taking medication had a 18% lower risk of developing Alzheimer's disease.
“Although we’re making progress with the new treatments for Alzheimer’s disease that work to clear amyloid plaques in the brain for people with early stages of the disease, we desperately need treatments that can prevent or delay the development of Alzheimer’s disease,” said study author Ruth Brauer, from University College London. “These results are encouraging and warrant further research.”
What's more, the risk reduction was greatest among men who took the most medication – 20 or more prescriptions over the study period. The data also suggested that the drugs had a stronger protective effect for men aged 70 years or over, compared to those under 70.
Phosphodiesterase type 5 inhibitors (PDE5Is) had previously shown promising results in animal studies, but evidence in human populations has been inconclusive. Sildenafil, the first PDE5I, was developed for the treatment of hypertension and angina, before it proved to be a game-changer for treating erectile dysfunction. The drug, which dilates blood vessels to boost blood flow, was repurposed in 2005 to treat pulmonary arterial hypertension.
There has also been research into using sildenafil as an obesity treatment and to lower risk of colorectal cancer.
The way the drug increases blood flow may also affect the brain, boosting circulation to potentially prevent the buildup of toxic proteins linked to Alzheimer's disease. In previous animal studies, PDE5Is also increased the neurotransmitter acetylcholine. This chemical plays a role in memory, learning and involuntary muscle movement, and low levels have been associated with Alzheimer's.
While promising, the researchers caution that this study should be seen as a starting point for further clinical investigation to understand just how PDE5Is work on the brain. Previous research has been met with reservations, with experts pointing to lifestyle variables and other factors that 'muddy the waters' in these kinds of studies.
“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 said. “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 was published in the journal Neurology.
Source: American Academy of Neurology
