Erectile Dysfunction Drugs as Potential Therapy for Cognitive Decline: Preclinical and Translational Evidence

Erectile dysfunction (ED) and cognitive decline share overlapping vascular, metabolic, and neurodegenerative mechanisms, particularly in aging populations. Phosphodiesterase type 5 inhibitors (PDE5-Is), such as sildenafil and vardenafil, are widely used to treat ED by elevating cyclic guanosine monophosphate (cGMP) levels and enhancing vascular function. Emerging evidence suggests that PDE5-Is may also benefit cognitive function by promoting neurovascular coupling, synaptic plasticity, and neuroprotection. This review synthesizes clinical, preclinical, and mechanistic studies on PDE5-Is in the context of learning, memory, and Alzheimer’s disease, highlighting their potential as therapeutic agents for cognitive impairment.