PDE5 inhibitor drugs for use in dementia
Abstract
Alzheimer's disease and related dementias (ADRD) remain a major health‐care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase‐5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia. Potent, selective, Food and Drug Administration–approved PDE5 inhibitors are already in clinical use (sildenafil, vardenafil, tadalafil) as vasodilators in erectile dysfunction and pulmonary arterial hypertension. Animal data indicate cognitive benefits of PDE5 inhibitors. In humans, real‐world patient data suggest that sildenafil and vardenafil are associated with reduced dementia risk. While a recent clinical trial of acute tadalafil on cerebral blood flow was neutral, there may be chronic actions of PDE5 inhibition on cerebrovascular or synaptic function. We provide a perspective on the potential utility of PDE5 inhibitors for ADRD. We conclude that further prospective clinical trials with PDE5 inhibitors are warranted. The choice of drug will depend on brain penetration, tolerability in older people, half‐life, and off‐target effects.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2023
- Source ID
- 10.1002/trc2.12412
Entities
People
- Atticus H Hainsworth
- Fanny M. Elahi
- Feixiong Cheng
- Jeremy D. Isaacs
- Ottavio Arancio
Organizations
- Alzheimer's Association
- British Heart Foundation
- Case Western Reserve University
- Chan Zuckerberg Initiative
- Columbia University
- Genomic Medicine Institute
- Icahn School of Medicine at Mount Sinai
- Larry L. Hillblom Foundation
- National Institutes of Health
- Rainwater Charitable Foundation
- St George's University Hospitals NHS Foundation Trust
- St George's, University of London
- United States Department of Defense