No association of Viagra and Cialis with reduced risk of Alzheimer’s disease

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Of NIH Research Questions

Efforts to develop new drugs to treat Alzheimer’s disease (AD) have yet to yield significant clinical benefits. A recent approach to developing treatments for AD is to search for existing FDA-approved drugs that could potentially be repurposed.

Computational methods have suggested that a class of existing drugs called phosphodiesterase-5 (PDE5) inhibitors could be used to treat AD. These drugs include sildenafil (Viagra) and tadalafil (Cialis). Both are approved for the treatment of erectile dysfunction and pulmonary hypertension, a type of high blood pressure that affects the arteries of the lungs and heart.

A previous NIH-funded study found that people taking sildenafil were less likely to develop AD. Sildenafil also reduced some AD-associated molecular abnormalities in cultured nerve cells derived from AD patients.

Among those looking for existing drugs that could treat AD are a team of researchers from the NIH’s National Institute on Aging (NIA) led by Dr. Madhav Thambisetty. In their new study, the team sought to verify previous findings about PDE5 inhibitors. Their results appeared in brain communications on October 4, 2022.

Both studies looked at insurance claims data from Medicare beneficiaries, but took different approaches. The previous study compared people who took sildenafil for any reason to those who didn’t. Since most people tend to take sildenafil for erectile dysfunction, this approach might have created differences between people in the two groups that could not be corrected based on the information in the medical claims.

In contrast, the current study focused on people with pulmonary arterial hypertension. The researchers compared the incidence of Alzheimer’s disease and related dementias in people treated with sildenafil or tadalafil versus those treated with another class of drugs. This made the two comparison groups more likely to have people with similar characteristics. The study included data on more than 13,000 people.

The team found no significant difference in AD and related dementia risk between the two treatment groups. The researchers analyzed the data in four different ways to address various possible biases in the data. None of these analyzes found a significant effect of PDE5 inhibitor treatment on the risk of Alzheimer’s disease or related dementias.

The researchers also looked at the effect of sildenafil on a range of molecular characteristics associated with AD in cell cultures. Although sildenafil had a modest anti-inflammatory effect, no protective effect was seen on the other outcomes tested.

The results do not support the use of PDE5 inhibitors such as sildenafil for the treatment of AD. This contrasts with previous results. The authors of the new study attribute the discrepancy primarily to differences in the design of the two studies, particularly in the selection of treatment and control groups.

“Combining routinely collected healthcare data with experimental studies to test potential drug reuse in Alzheimer’s disease is a powerful approach,” Thambisetty said. “It can help us discover promising drugs to test in rigorous clinical trials.”

by Brian Doctrow, Ph.D.

Reference: Desai RJ, et al. No association between initiation of phosphodiesterase-5 inhibitors and risk of incidence of Alzheimer’s disease and related dementia: results from the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study. Cerebral communications. 2022. doi: 10.1093/braincomms/fcac247.

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