Can Viagra reduce the risk of Alzheimer’s disease? – What is behind the news?

In recent months, there have been repeated reports that Viagra, the famous drug used against erectile dysfunction, could reduce the risk of Alzheimer’s disease. At first glance, this seems to be an interesting therapy option, once Alzheimer’s disease is the leading cause of dementia in individuals over 65 and has a major negative impact on the lives of patients, relatives and caregivers. Furthermore, it generates a large economic and financial burden for both the patient’s family and healthcare systems. 

The search for an effective drug against this and other forms of dementia has been one of the priorities in the field of science, but without positive results so far. We know that the development of new drugs is a time-consuming and costly process. Thus, the possibility of redirecting a drug already licensed for other health conditions, using it for the treatment of AD, could accelerate the process and benefit a large number of patients with less expense. 

Bearing this in mind, a team of researchers from the Cleveland Clinic has developed a computerised method to identify which of the medications approved by the Food and Drugs Administration (FDA), the US health agency, could be effective in preventing Alzheimer’s disease. 

The researchers created two information networks: the first one mapped the proteins related to pathological and molecular alterations of Alzheimer’s disease, such as amyloid plaques and neurofibrillary tangles; the second one mapped the more than 1600 drugs approved by the FDA considering their molecular action target, that is, in which pathological aspect each drug would act. 

By calculating the relationship between the components of the two networks, the team identified 66 drugs with a closer association with the pathogenesis of Alzheimer’s, i.e., drugs that would act directly on molecular processes involved in causing Alzheimer’s disease. Some of these drugs are already being tested for Alzheimer’s disease treatment through clinical trials, such as losartan and metformin. Sildenafil, also known as Viagra, had not yet been tested for this purpose, but presented itself, according to these calculations, as the best candidate. 

Subsequently the team of researchers analysed the health plan usage data of over 7 million Americans and noted that people (mainly men) who took sildenafil were 69% less likely to develop Alzheimer’s disease in 6 years than those who did not take the drug. This result strengthened the conclusions found by the computerised method described above. 

In vitro studies using cells from Alzheimer’s patients have shown that, when exposed to Sildenafil, such cells show increased neuronal connections and reduced phosphorylation of Tau protein – a biomarker of the disease. All these findings together corroborate to indicate Sildenafil as a potential weapon in the prevention and treatment of Alzheimer’s disease. 

 

What is the mechanism of action of Sildenafil and its role in preventing Alzheimer’s disease? 

Sildenafil, popularly known as Viagra, is a drug used for erectile dysfunction and pulmonary hypertension (increased pressure in the arteries of the lungs). Its mechanism of action results in vasodilation, i.e. the relaxation of the muscles of the arterial vessel wall, promoting greater blood flow to the tissues.  

Hemodynamic alterations, i.e., changes in blood circulation in brain tissue, are observed in patients with Alzheimer’s Disease and can be documented by imaging examinations. Such changes include reduced cerebral blood flow (CBF), increased cerebrovascular resistance, and reduced cerebral metabolic rate. Improved blood flow to the brain could, in theory, reduce the risk of developing Alzheimer’s disease. 

 

So, what concrete information does this new study bring? 

The results of this study published in Nature Aging in 2021, although encouraging, show only an association between sildenafil and reduced risk of Alzheimer’s disease, but are not able to demonstrate causality – that is, there is no evidence that taking sildenafil is the cause of reduced risk of Alzheimer’s in the studied population. 

Furthermore, the observation period was only six years, which is too short for a long progressive disease like Alzheimer’s dementia. Moreover, one should also consider that men who go to the doctor for erectile dysfunction are already different from those who are pre-symptomatically affected by Alzheimer’s disease. Another criticism of this study is that the proportion of women in the study was naturally low, but in fact women have a greater risk of developing Alzheimer’s disease. 

This study has raised hope in a large proportion of dementia’s researchers. However, controlled clinical trials have yet to be conducted to assess the long-term clinical benefits of sildenafil in Alzheimer’s and to prove the cause-and-effect relationship.  For now, this association is just an interesting hypothesis that demands further testing for proof before “reducing the risk of Alzheimer’s disease” enters the list of indications for the use of Sildenafil. 

Although the study is scientifically of great interest, we do not recommend using Viagra exclusively for this purpose, as there is not yet strong evidence of a corresponding effect.   

 

Conclusion:  

Science has long been searching for a drug that can reduce the risk of Alzheimer’s disease. A new study has used the methodology of computer-assisted data analysis to find candidates among already approved drugs for other indications that could also be effective in Alzheimer’s disease. Here, the Viagra active ingredient sildenafil, a drug used to treat erectile dysfunction and pulmonary hypertension, has emerged as a promising candidate.  Although the study brings us hope of finding a drug that can prevent this devastating disease, its results need to be proven by clinical trials that assess long-term efficacy and safety.  

We do not advise the use of Viagra for this purpose as we do not yet have consistent evidence. Moreover, it is now well established that drug monotherapies are not the sole solution for effective causal Alzheimer’s treatment. To date, the multifactorial lifestyle changes described in our project are the most effective – and above all the most side-effect-free – form of prevention and treatment of AD. 

We, the team of Knowledge stops Dementia, will keep you well informed! 

Reference: 

Fang, J., Zhang, P., Zhou, Y. et al. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nat Aging 1, 1175–1188 (2021). https://doi.org/10.1038/s43587-021-00138-z