2024-03-07 13:39:06
According to recent research, men prescribed medications to treat newly diagnosed erectile dysfunction (ED) have an 18% lower risk of developing Alzheimer’s disease during a 5-year follow-up period. The results were in Neurology published [1].
The study is the 2nd in recent years to indicate an association between the use of phosphodiesterase type 5 inhibitors (PDE5I) such as sildenafil (Viagra®) or tadalafil (Cialis®) and the risk of Alzheimer’s disease. The results contradict those of a third study in which no association was found.
Interpret results with caution
Although the research results are interesting, experts point out the lack of evidence for treating Alzheimer’s with these drugs and urge caution when interpreting the results.
The authors agree, but believe their results provide impetus for future studies. The results also underline how important it is to find out whether therapies that have already been approved can be repurposed to treat Alzheimer’s.
“The positive results from our large study of over 250,000 men are promising and can be used to improve research capacity and knowledge, potentially impacting clinical use and health policy in the future,” said lead author Dr. Ruth Brauer from University College London (Great Britain) opposite Medscape. “Before recommending the use of PDE5I to reduce the risk of Alzheimer’s disease, further work is needed to validate our results – particularly in a generalizable population that includes women and men without erectile dysfunction.”
Before recommending the use of PDE5I to reduce the risk of Alzheimer’s disease, further work is needed to validate our results. Dr. Ruth Brauer
Study shows strong association
The study was based on primary health care data in the United Kingdom. It includes 269,725 men (mean age 59 years) with newly diagnosed ED, 55% of whom had been prescribed PDE5I.
Participants had no memory or cognitive problems at the start of the study. They were followed up for a median of 5.1 years. The scientists considered a number of potential risk factors for Alzheimer’s, including smoking status, alcohol consumption, body mass index, high blood pressure, diabetes, depression, anxiety and concurrent use of various medications.
During the study period, 749 people in the PDE5I group were diagnosed with Alzheimer’s disease, a rate of 8.1 cases per 10,000 person-years. Among those who didn’t take the medication, 370 developed Alzheimer’s disease, a rate of 9.7 cases per 10,000 person-years.
Overall, taking a PDE5I was associated with an 18% lower risk of Alzheimer’s disease compared to people not taking medication (adjusted hazard ratio [aHR] 0.82; 95%-TO 0,72-0,93).
The association was stronger in people aged 70 or older and in people with a history of high blood pressure or diabetes. The greatest risk reduction was seen among individuals with the most prescriptions during the study period. The results:
Those with 21-50 prescriptions had a 44% lower risk of Alzheimer’s disease (aHR 0.56; 95% CI 0.43-0.73).
Those with more than 50 prescriptions were 35% less likely to be diagnosed with Alzheimer’s disease (aHR 0.65; 95% CI 0.49-0.87).
There was no association with Alzheimer’s risk among people who received fewer than 20 prescriptions.
The scientists also analyzed the associations after introducing a 1- and 3-year lag period after cohort entry to account for the latency between the onset of Alzheimer’s disease and diagnosis. The primary outcomes persisted at a 1-year lag but lost significance at a 3-year lag.
In subgroup analyses, there was evidence of a lower risk of Alzheimer’s disease in patients prescribed sildenafil (aHR 0.81; 95% CI 0.71-0.93). However, there was no evidence of a lower risk in patients receiving tadalafil and vardenafil compared to non-users.
A lower risk of Alzheimer’s disease was found in patients with high blood pressure, diabetes and in men aged 70 or older. However, there was no association in younger men or in men without a history of high blood pressure or diabetes.
Although the scientists considered a variety of potential risk factors, Brauer noted that unmeasured confounders could have influenced the results. These include, for example, physical and sexual activity, which were not recorded and may influence PDE5I exposure.
Experts warn against using the active ingredients too early
Dr. Ozama Ismail, director of scientific programs at the Alzheimer’s Association, commented on the results for Medscape. He pointed out an additional limitation not listed in the publication: Alzheimer’s diagnoses were not made using the “gold standard,” which typically includes imaging biomarkers and postmortem examinations.
“While this study is interesting and suggests a possible association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Ismail, who was not involved in the current study.
“Based on this preliminary finding, over-the-counter phosphodiesterase type 5 inhibitors should not be used to prevent Alzheimer’s disease or other dementias. Always consult your doctor before starting or changing any medication,” Ismail cautioned.
However, the study shows a potential new path for the development of new therapies using already approved active ingredients. This saves time and money.
“However, when considering using an existing drug to treat Alzheimer’s disease, new studies often need to be conducted over longer periods of time and in older people. This is the only way to reflect the diversity of Alzheimer’s patients, says Ismael.
Based on this preliminary finding, over-the-counter phosphodiesterase type 5 inhibitors should not be used to prevent Alzheimer’s disease or other dementias. Dr. Ozama Ismail
Randomized trials are needed
Brauer agrees. She suggests that such a study should also include people with mild cognitive impairments. It was also intended to measure the effects of PDE5Is at predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor.
“The primary endpoint would be change from baseline in cognitive function,” she says. “This approach would enable a comprehensive understanding of the potential therapeutic benefits of PDE5I in Alzheimer’s disease.”
Studies are also needed to better understand the mechanisms by which these drugs may influence Alzheimer’s risk, said Dr. Sevil Yasar and Dr. Lolita Nidadavolu from the Department of Geriatric Medicine and Gerontology at the Johns Hopkins University School of Medicine in Baltimore, Maryland.
The strong association between PDE5I use and the risk of Alzheimer’s disease in people with a history of hypertension or diabetes suggests a “possible neuroprotective effect via a vascular pathway,” they write.
In vitro studies on the role of inflammation and clearance of beta-amyloid could corroborate the results of studies such as this one. And in vivo studies could help explain the mechanisms behind PDE5I use and the lower risk of Alzheimer’s disease, Yasar and Nidadavolu said.
“Ultimately, however, further observational studies exploring the mechanisms will not prove a causal relationship,” they write. “A well-designed randomized controlled trial is required before PDE5I drugs can be prescribed to prevent Alzheimer’s disease.”
The article originally appeared on Medscape.com.
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