Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows.
The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by Medscape Medical News, that showed no link between the two.
Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings.
Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD.
“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London in the United Kingdom, told Medscape Medical News.
“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.
The findings were published online February 7 in Neurology.
The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is.
Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.
During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.
Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions.
The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).
There was no association with AD risk in individuals who received fewer than 20 prescriptions.
Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.
In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.
Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes.
Although investigators controlled for a wide range of potential risk factors, Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results.
Interpret With Caution
Commenting on the findings for Medscape Medical News, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments.
“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Brauer, who was not part of the current study.
“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” Ismail cautioned.
However, Ismael added that the study does highlight a potential new avenue for drug repurposing.
“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said.
“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Ismael said.
Randomized Trials Needed
Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor.
“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”
Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, noted Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, in an accompanying editorial.
The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.
In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Yasar and Nidadavolu noted.
“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”
The study was unfunded. The study and editorial authors and Ismail report no relevant financial conflicts.
Kelli Whitlock Burton is a reporter for Medscape who covers neurology and psychiatry.
Source link : https://www.medscape.com/viewarticle/more-data-show-erectile-dysfunction-meds-may-affect-2024a10002q3?src=rss
Publish date : 2024-02-07 21:05:11
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