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Could Erectile Dysfunction Drugs Be Linked to Reduced Alzheimer’s Risk?

A blue pill.
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A new observational study from University College London (UCL) researchers has concluded that men prescribed drugs for erectile dysfunction were 18% less likely to develop Alzheimer’s disease years down the line.

Potential to repurpose

Drugs such as sildenafil (also known as Viagra) were first developed to treat high blood pressure and angina. They work by inhibiting the enzyme phosphodiesterase type 5 (PDE5) to dilate blood vessels and induce smooth muscle relaxation, which enabled them to be repurposed for erectile dysfunction (ED).

Now, these drugs could be repurposed again, with early evidence from an observational study suggesting they may have the potential to prevent Alzheimer’s disease (AD).

AD is the most common form of dementia, with approximately 5.5 million people in the US living with the disease. It currently has no cure – though the first drugs to treat AD are beginning to enter the market.

PDE5 inhibitors (PDE5Is) used to treat ED can also cross the blood–brain barrier, where it is expected that they may act on signaling molecules in the brain. Some animal studies have suggested that PDE5Is may have neuroprotective effects, but studies investigating associations between these drugs and AD in humans have had conflicting results and aren’t easily comparable.

Given these discrepancies, the new observational study from UCL researchers aimed to explore this area further. They used prescription records to investigate the association between PDE5Is and the risk of developing AD for men with ED. The research is published in the journal Neurology.

ED drugs may provide benefits for Alzheimer’s risk reduction

The study looked at the electronic health records of 269,725 men over the age of 40 diagnosed with ED. Importantly, these participants did not have a previous diagnosis of dementia, cognitive impairment or confusion.

The researchers compared data from men prescribed PDE5Is (i.e., sildenafil, tadalafil, vardenafil and avanafil) against those with no prescription (non-users).

Over a median follow-up of 5.1 years, 1,119 of the participants were diagnosed with AD. Of these, 749 were prescribed ED drugs while 370 were not. This equates to 8.1 AD cases per 10,000 person-years for those with a prescription, and 9.7 cases per 10,000 person-years for those without.

What are person-years?

Person-years represent both the number of people in the study and the amount of time they participate in the study. This is another way to measure disease incidence.

After adjusting for factors such as age, underlying health conditions and smoking, the analysis concluded that men prescribed ED drugs were 18% less likely to develop AD.

This effect was stronger for patients who had been issued more prescriptions, suggesting that frequent use could have a greater influence on AD risk.

“The risk appears to be dose-dependent, i.e., higher risk reduction with more prescriptions,” explained Dr. Ivan Koychev, a senior clinical researcher at Dementia Platform UK, who was not involved in the study. “It is also more pronounced in people with heart disease risk factors (high blood pressure, diabetes), suggesting that the effect may be due to neuroprotection through vascular mechanisms.”

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“Overall, this is a significant development as repurposing already existing drugs for the prevention of dementia is a promising strategy to stop dementia from developing in the first place using drugs with known safety profiles,” Koychev added.

Additional studies and evidence needed

Nonetheless, the study’s design does somewhat limit the conclusions it can draw as it was based on prescription records. This means it isn’t known exactly how much of the medication patients took or how frequently.

Additionally, this was an observational study, meaning it cannot be used to determine a causal relationship, though it does provide worthwhile evidence to conduct further studies. Large and robust randomized control trials are required to investigate the potential of these drugs to prevent AD compared to a placebo.

“Such studies should also uncover whether these drugs might have effects in other groups, such as women and men without a diagnosis of erectile function,” said Dr. Leah Mursaleen, head of research at Alzheimer’s Research UK. “We also need to understand how this evidence might apply to more diverse populations.”

Reference: Adesuyan M, Jani YH, Alsugeir D, et al. Phosphodiesterase type 5 inhibitors in men with erectile dysfunction and the risk of Alzheimer disease. Neurology. 2024;102(4):e209131. doi: 10.1212/WNL.0000000000209131