Can Viagra Reduce Risk of Alzheimer’s Disease? You Must Know
Doctors prescribe Sildenafil - popularly known by its brand name Viagra - to treat erectile dysfunction and pulmonary arterial hypertension, which refers to high blood pressure in the lungs. However, several studies in mice and some pilot studies in humans have suggested that sildenafil could also treat Alzheimer's disease.
A new study has now provided biological and population-based evidence that supports the idea that the drug can help prevent and treat the disease.
"Developing brain drugs for diseases such as Alzheimer's disease is an expensive process and can take many years," said Dr. Susan Kohlhaas, Ph.D., director of research at Alzheimer's Research UK in the UK, told Medical News Today.
"The ability to reuse a drug that has already been approved for other diseases could help accelerate the drug discovery process and bring about life-changing treatments for dementia earlier," she said.
The study, led by the Cleveland Clinic's Genomic Medicine Institute in Cleveland, OH, appears in Nature Aging.
In Alzheimer's disease, the most common form of dementia, the death of brain cells leads to progressive memory loss and cognitive decline.
Given our aging population, scientists predict that by 2050, 13.8 million people will develop Alzheimer's disease in the United States alone.
Alzheimer's disease hallmarks
The main characteristics of the disease in the brain are plaques of a protein called beta-amyloid and fibrous tangles of tau, another protein.
However, so far, clinical trials of drugs and vaccines targeting the two proteins have shown disappointing results from.
A complex interplay of genes and environmental factors causes Alzheimer's.
To predict which existing drugs could offer new treatment options, the researchers used a computer model that incorporates data about the genetics of the disease and the metabolic pathway networks involved.
In particular, they focused on interactions between proteins in networks that play a role in the formation of beta amyloid and tau.
Next, they generated “network proximity measures” for over 1,600 approved drugs, depending on how closely they interact with these Alzheimer's-related networks.
This enabled the scientists to narrow the field down to 66 drugs that could potentially treat the disease. Taking into account other considerations, such as promising results from experiments in animal models of Alzheimer's disease, sildenafil has emerged as the most promising candidate.
The researchers further investigated by analyzing insurance claims for prescriptions from 7.23 million people in the United States.
Overall, they found that applicants who were prescribed sildenafil had a 69% reduced risk of Alzheimer's disease over the next 6 years.
The association remained statistically significant after considering other factors that influence Alzheimer's risk, such as gender, race, and other diseases. These conditions included type 2 diabetes, high blood pressure, coronary artery disease, and mild cognitive impairment.
Finally, to confirm that sildenafil can affect the underlying mechanism of Alzheimer's disease, the researchers tested the drug in the laboratory on nerve cells derived from people with the disease.
They found that sildenafil promoted the growth of new nerve protrusions and decreased the build-up of dew in the cells.
Researchers often use tau as a biomarker to measure disease progression in animal models and humans.
Cause and effect?
The authors point out that their study design cannot demonstrate a causal relationship between the use of a particular drug and the risk of Alzheimer's disease.
They say there could be hidden confounders that affect not only your Alzheimer's risk, but your likelihood of taking sildenafil as well.
Possible disruptive factors that were not taken into account in the insurance data are the level of education and socio-economic status.
However, there was no significant difference in the total annual cost of prescriptions between sildenafil users and non-users, suggesting that the two groups did not differ in terms of wealth.
The authors believe their laboratory results support the conclusion that sildenafil is a potential treatment.
"[W] I don't think socioeconomic status will determine our results, as we have further validated our results in [Alzheimer's] patient-based [nerve cells] models," said senior author Feixiong Cheng, Ph.D. MNT.
The authors also note that the insurance data did not include genetic information, such as whether applicants had a particular version of the apolipoprotein E gene that increases the risk of Alzheimer's disease and affects patients' response to treatment.
Additionally, medical professionals primarily prescribe sildenafil to men, so the study did not identify any potential benefit to women in terms of Alzheimer's risk.
"Although the researchers examined the effects of sildenafil in women, there is not enough information to be able to draw precise conclusions about its effects in women, who make up the majority of Alzheimer's cases worldwide," said Dr. Kohlhaas.
"Importantly, this research does not prove that sildenafil is responsible for reducing the risk of dementia or slowing or stopping the disease," she said.
"The only way to test this would be a large-scale clinical trial to measure the effects of sildenafil against the usual standard of care."
The authors conclude:
“Taken together, the association between sildenafil use and a reduced incidence of [Alzheimer's disease] does not reveal any causality or direction, and our results therefore warrant rigorous clinical studies of the effectiveness of sildenafil in patients with [Alzheimer's disease], including both sexes and controlled by placebo. "
"We are planning a mechanistic study and a biomarker-driven phase 2 study in the next step to further verify [the] clinical benefits of sildenafil in patients with [Alzheimer's disease] in the early stages," said Dr. Cheng across from MNT.
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