Phosphodiesterase‐5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia (1).
Phosphodiesterase‐5 (PDE5) inhibitors are in clinical use as vasodilators (1)
- in animals PDE5 inhibitors enhance synaptic function and cognitive ability
- primary clinical effects of PDE5I are a result of raised cyclic guanosine monophosphate (cGMP), a secondary messenger that is degraded by the phosphodiesterase enzyme (PDE) (2)
- studies have shown low levels of cGMP in tandem with raised levels of PDE in the brains of people with Alzheimer's disease
- is evidence that in humans the PDE5 inhibitor sildenafil is associated with reduced risk of Alzheimer's disease (1)
A UK cohort study of men aged ≥40 years with a new diagnosis of erectile dysfunction (n=269,725) found the initiation of PDE-5 inhibitors was associated with a decreased risk of Alzheimer’s disease compared with non-users (adjusted HR 0.82, 95% CI 0.72–0.93) (2):
- sensitivity analysis with a 1-year lag period (excluding those with less than 1 year of follow-up after cohort entry) supported the primary findings (HR 0.82, 95% CI 0.72–0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80–1.08)
- study authors state that this highlights the need to explore the optimal lag period, and they call for a randomised controlled trial including both men and women, exploring various PDE-5 inhibitor doses, to confirm their findings in a wider population
Reference:
- Hainsworth AH, Arancio O, Elahi FM, Isaacs JD, Cheng F. PDE5 inhibitor drugs for use in dementia. Alzheimers Dement (N Y). 2023 Sep 25;9(3):e12412.
- Adesuyan M et al.Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease
A Cohort Study. Neurology February 7th 2024.