February 7, 2024

expert reaction to observational study of erectile dysfunction drugs and risk of Alzheimer’s Disease

A study published in Neurology looks at erectile dysfunction drugs and risk of Alzheimer’s Disease.

Dr Francesco Tamagnini, Neurophysiologist at the Reading School of Pharmacy, University of Reading, said:

“The role of nitric oxide neurotransmission in the consolidation, encoding and retrieval of memory has been known for a few years. Nitric oxide is both involved peripherally on erectile function (by mediating vasodilation) and centrally in cognition, by modulating neuronal function. For example, nitric oxide dependent transmission has been observed as needed for perirhinal cortex-dependent visual recognition memory (Tamagnini et al., 2013).

“In theory it is possible that promoting nitrergic transmission could improve memory function, but the question remains whether the observed association is describing a direct effect. This is a great study but more hard evidence is needed to test a mechanism of action. It could be that it exerts a therapeutic effect directly affecting neurons (if the drug is able to cross the blood brain barrier) and/or by increasing blood flow but both these hypotheses need to be tested.”

Dr Ivan Koychev, Senior Clinical Researcher, Dementia Platform UK, University of Oxford, said:

“This is a large study demonstrating a relationship between prescription of phosphodiesterase type 5 inhibitors and reduced risk of Alzheimer’s disease in men. The risk appears to be dose-dependent i.e. higher risk reduction with more prescriptions. 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. 

“The study is limited through the challenge in drawing causal relationships in epidemiological studies. Also, these types of drugs is typically taken as needed, so it is difficult to know how much was actually taken and at what frequency. In addition, the link to Alzheimer’s disease in particular is contentious as it is known that a significant proportion of dementia cases diagnosed as Alzheimer’s clinically have additional or alternative pathologies. 

“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 profile. Clinical trials where these drugs are given against a dummy pill to people at risk are required to decide on their usefulness for dementia prevention. It is worth noting that the blinding of such trials (i.e. ensuring that neither the patients nor researchers know what is given) will be limited given the physiological effects of the drugs.”

Dr Leah Mursaleen, Head of Research at Alzheimer’s Research UK, said:

“Developing drugs for diseases like Alzheimer’s is a costly process and can take many years. Being able to repurpose drugs already licensed for other health conditions could help accelerate progress and open up new avenues to prevent or treat dementia-causing diseases.

“This research looked at medical records of nearly 270,000 men with erectile dysfunction, and found that those prescribed drugs known as PDE5Is – including common brand name Viagra – also appeared to have a lower risk of developing Alzheimer’s.

“While this is an encouraging finding, it doesn’t yet confirm whether these drugs are directly responsible for reducing Alzheimer’s risk, nor whether they can slow or stop the disease.  Further research – including clinical trials – will be needed to confirm whether these drugs can indeed play a role in preventing or treating Alzheimer’s. 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. We also need to understand how this evidence might apply to more diverse populations.. The only way to do this is to keep up momentum in dementia research through continued investment.”

“If you want to discuss any treatments you are taking, your first port of call is to speak to your doctor.”

Prof Tara Spires-Jones, President of the British Neuroscience Association and Professor at the UK Dementia Research Institute at the University of Edinburgh, said:

“This study by Adesuyan and colleagues found an association between prescription of drugs used to treat erectile dysfunction and a reduced risk of developing Alzheimer’s disease. The study was well-conducted, and authors are appropriately cautious in their interpretation of the data. This study does not conclusively prove that erectile dysfunction drugs reduce Alzheimer’s risk but provide good evidence that this type of drug is worth further study in future.”

‘Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease’ by Matthew Adesuyan et al. was published in Neurology at 21:00 UK time on Wednesday 7th February.

DOI: 10.1212/WNL.0000000000209131

Declared interests

Prof Tara Spires-Jones: I have no conflicts with this study.

For all other experts, no reply to our request for DOIs was received.