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Could PDE5 inhibitors benefit dementia?

Atticus Hainsworth, St George’s University of London, London, UK comments on recent investigations into the use of PDE5 inhibitors in dementia. A session at the AAIC 2022 meeting was dedicated to new research on this topic. Work was presented by Feixiong Chen from the Cleveland Clinic who used an endophenotype disease module-based methodology for Alzheimer’s disease (AD) drug repurposing, which identified sildenafil as a potential disease risk modifier. Data from over 7 million individuals showed that sildenafil usage was significantly associated with a 69% reduced risk of AD. Studies in iPSC-derived neurons developed from AD patients further showed that sildenafil increases neurite growth and decreases phospho-tau expression. Dr Hainsworth comments on future research endeavors that have arisen from Dr Chen’s observations, most notably further investigation into the effects of chronic usage of sildenafil and the potential mechanistic links with dementia risk. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.