Hainsworth, AH; Arancio, O; Elahi, FM; Isaacs, JD; Cheng, F
(2023)
PDE5 inhibitor drugs for use in dementia.
Alzheimer's and Dementia: Translational Research and Clinical Interventions, 9 (3).
e12412.
ISSN 2352-8737
https://doi.org/10.1002/trc2.12412
SGUL Authors: Hainsworth, Atticus Henry
|
PDF
Published Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
|
|
PDF (Supplementary information)
Published Version
Available under License Creative Commons Attribution. Download (366kB) | Preview |
|
![]() |
Microsoft Word (.docx)
Accepted Version
Available under License Creative Commons Attribution. Download (231kB) |
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. HIGHLIGHTS - Potent phosphodiesterase-5 (PDE5) inhibitors are in clinical use as vasodilators. - In animals PDE5 inhibitors enhance synaptic function and cognitive ability. - In humans the PDE5 inhibitor sildenafil is associated with reduced risk of Alzheimer's disease. - Licensed PDE5 inhibitors have potential for repurposing in dementia. - Prospective clinical trials of PDE5 inhibitors are warranted.
Item Type: | Article | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Additional Information: | © 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Alzheimer's and Dementia: Translational Research and Clinical Interventions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2352-8737 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dates: |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher License: | Creative Commons: Attribution 4.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projects: |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/115530 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher's version: | https://doi.org/10.1002/trc2.12412 |
Statistics
Actions (login required)
![]() |
Edit Item |