Researchers from the University College London Hospitals point out that repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for AD risk reduction has shown promise in animal studies, but evidence in humans has remained inconclusive.
To remedy that, the study team conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with ED. Results were published in the journal Neurology.
The researchers used electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database) to identify men aged 40 years or older with a new diagnosis of ED between 2000 and 2017. The study excluded men with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms.
The study team then used diagnostic read codes to identify any occurrence of incident AD. A secondary analysis examined the association between AD and the cumulative number of PDE5I prescriptions.
The study ultimately included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93).
Results indicate that the associated risk of AD decreased in men receiving more than 20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21 to 50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for more than 50 prescriptions. “Sensitivity analysis with a 1-year lag period 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),” the authors explained.
“PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions,” according to the study. “The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized, controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.”
Background information in the article noted that PDE5Is are one of the most widely used drugs that have been repurposed. “Sildenafil, the first PDE5I, was originally developed for the treatment of hypertension and angina,” the researchers advised.
“The intended vasodilatory effects were also found to cause smooth muscle relaxation in the corpus cavernosum, making sildenafil (Viagra) an effective repurposed treatment option for erectile dysfunction (ED). The repurposing possibility of PDE5I continued beyond ED, and in 2005, sildenafil also became licensed for the treatment of pulmonary arterial hypertension (PAH).”
The study explains that the primary clinical effects of PDE5I are a result of raised cyclic guanosine monophosphate, a secondary messenger that is degraded by the phosphodiesterase enzyme. It noted that two cohort studies investigating the association between PDE5I and AD were conducted in the United States—one finding that use of sildenafil in older adults was associated with a 69% reduced risk of AD compared with nonuse, and the other determining no evidence of association between PDE5I and risk of AD when compared with endothelin receptor antagonists in patients with PAH.
“Given the discrepancy in findings between previous studies and the clinical data supporting the potential repurposing effects of PDE5I on neurologic disease, we conducted a large population-based cohort study to determine whether the use of PDE5I compared with nonuse is associated with a lower risk of AD in a homogenous population of men with ED, the authors explained.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
