According to i According to the results of a study published in Neurology, the use of phosphodiesterase 5 (PDE5i) inhibitors in men with erectile dysfunction is associated with a reduced risk of developing incident Alzheimer’s disease. «According to estimates, 57 million people in the world suffer from dementia and the forecasts for 2050 bring this number to 157 million» begin the authors, coordinated by Ruth Brauer of University College London (United Kingdom), recalling that Alzheimer’s disease is the most common form of dementia.
As Brauer and colleagues point out, research is making progress in identifying therapies that can reduce amyloid plaques in patients with early-stage disease, but interventions are still needed to prevent or delay the development of this dementia.
A link to be investigated
Numerous studies conducted on animal models have suggested a possible neuroprotective effect linked to the use of PDE5i, but the results in humans do not allow definitive conclusions to be reached.Hence the idea of carrying out a study on a large and homogeneous population to understand whether the use of PDE5i compared to non-use was associated with a lower risk of Alzheimer’s.
Based on information from the IQVIA Medical Research Data UK database, Brauer and colleagues identified men aged 40 and older diagnosed with erectile dysfunction and with no previous diagnosis of dementia, confusion or cognitive decline.
Out of a total of 269,725 men enrolled in the study, 1,119 developed Alzheimer’s disease during the 5-year follow-up, and the analysis adjusted for potential confounders showed an 18% reduction in the risk of developing this dementia (Hazard Ratio [HR]: 0.82) in those who used PDE5i compared to those who did not use them.
«The risk reduction was greater in men who received a greater number of prescriptions for PDE5i during follow-up,» explain the authors, who also conducted a sensitivity analysis establishing two different «lag» periods (1 and 3 years) to account for the prodromal phase of Alzheimer’s disease.
On balance, the sensitivity analysis with a delay period of 1 year confirmed the primary results (HR 0.82), as opposed to that with a delay period of 3 years (HR 0.93).
It’s not (yet) time for repurposing
The idea of repurposing a drug with a different indication than the one for which it was originally created represents a quick and cost-effective way to deploy new effective therapies.In particular, PDE5i are not new to such an approach: sildenafil, a molecule belonging to this class of drugs, was initially developed to treat hypertension and angina, but has become «famous» for the treatment of erectile dysfunction. Subsequently, the molecule was also approved for the treatment of pulmonary arterial hypertension.
Regarding the repositioning of PDE5i drugs in the neurological field, and in particular to counteract Alzheimer’s, the same authors are cautious and point out first of all that the new data highlight an association and not a cause-effect relationship.
«The results are based on prescriptions and not on actual drug use, and we cannot be sure that we have eliminated all potential confounding factors in the analysis,» Brauer and colleagues note, suggesting new studies in larger populations and including women to confirm the findings and make them more generalizable.
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