Phosphodiesterase type 5 inhibitors such as Viagra are known for their effectiveness in treating erectile dysfunction, but a study of nearly 270,000 men adds to growing evidence that they may also reduce the risk of Alzheimer's disease. Researchers at University College London (UCL) surveyed 269,725 male participants in the UK, with an average age of 59, no signs of cognitive impairment and who had recently been diagnosed with erectile dysfunction.
In the five-year study, researchers evaluated the men into two groups: those who were prescribed erectile dysfunction drugs such as sildenafil (Viagra) (55 percent of participants) and those who did not have their erectile dysfunction treated in this way (45 percent of participants).
They found that of 1,119 participants with Alzheimer's disease, 749 were taking erectile dysfunction medications, while 370 were not. But when measured in person-years (the number of people studied and the time each person spent in the study), the researchers found that the incidence rate of Alzheimer's was 8.1 cases per 10,000 years among those who took the medication, compared with 9.7 cases per 10,000 years among those who did not take erectile dysfunction drugs.
When other factors (age and lifestyle, such as smoking and drinking) were taken into account, the researchers found that those who took the medication had an 18 percent lower risk of developing Alzheimer's.
Study author Ruth Brauer of University College London said: "While we are making progress towards new treatments for Alzheimer's disease that clear amyloid plaques from the brain and help early-stage patients cure the disease, there is still an urgent need for therapies that can prevent or delay the progression of Alzheimer's disease. These results are encouraging and warrant further study."
What's more, men who took the drug the most often (20 or more times) during the study period had the greatest risk reduction. The data also showed that the drug was more protective in men aged 70 or older than in men younger than 70 years old.
Phosphodiesterase type 5 inhibitors (PDE5Is) have previously shown promising results in animal experiments, but the evidence in humans has been inconclusive. Sildenafil, the first PDE5I, was developed to treat high blood pressure and angina and later proved to be a game-changer in the treatment of erectile dysfunction. In 2005, the drug, which dilates blood vessels and promotes blood flow, was repurposed to treat pulmonary hypertension.
Sildenafil has also been studied as a drug to treat obesity and reduce the risk of colorectal cancer.
The way the drug increases blood flow may also affect the brain, boosting circulation and thus potentially preventing the buildup of toxic proteins associated with Alzheimer's disease. In previous animal experiments, PDE5Is also increased the neurotransmitter acetylcholine. This chemical plays a role in memory, learning and involuntary muscle movements, and low levels of acetylcholine have been linked to Alzheimer's disease.
The researchers caution that this study, while promising, should be considered a starting point for further clinical studies to understand how PDE5Is act in the brain. Experts note that lifestyle variables and other factors can "confound" such studies.
"More research is needed to confirm these findings, understand the potential benefits and mechanisms of these drugs, and investigate optimal dosing," Brauer said. "Randomized controlled trials with male and female participants are necessary to determine whether these findings also apply to women."
The research was published in the journal Neurology.