Few drugs have captured the world’s attention like Viagra (sildenafil). It changed the treatment of erectile dysfunction (ED) and became a household word. Most health professionals attribute sildenafil’s effectiveness to its ability to relax smooth muscle. This leads to the inflow of blood to the corpus cavernosum of the penis and a sustained erection. But the drug has a number of other pharmacological actions. Scientists at the Cleveland Clinic did an impressive job a few years ago exploring possible drugs to prevent Alzheimer disease (Nature Aging, Dec. 6, 2021). One that looks especially promising is sildenafil. Can Viagra help prevent dementia?
Evidence That Viagra Helps Prevent Dementia:
British scientists recently reported on some intriguing research involving drugs to treat erectile dysfunction (Neurology, Feb. 27, 2024). They reviewed 270,000 medical records of men who were at least 40 years old and newly diagnosed with erectile dysfunction. Those who already had a diagnosis of dementia or cognitive impairment were not included in the analysis.
During an average five-year follow-up, 1,119 men received a diagnosis of Alzheimer disease. Those taking ED drugs such as sildenafil or tadalafil were almost 20% less likely to develop dementia. The more frequently men used these drugs, the better the outcome. The authors call for randomized controlled trials to confirm their results showing that Viagra helps prevent dementia.
The Search for Old Drugs to Fight Alzheimer’s Disease:
Drug companies want above all to develop new treatments for hard-to-treat diseases. That’s because they can patent them and make tons of money. Very few pharmaceutical manufacturers are willing to spend money on medicines that have lost their patents and are available generically at low cost.
But repurposing old, inexpensive medications can be extremely helpful. The researchers at the Genomic Medicine Institute at the Cleveland Clinic wanted to do exactly that in their quest to find a drug that might work against Alzheimer disease. They completed this research prior to the British study described above.
The investigators targeted the interplay of two compounds in the Alzheimer disease model—tau and amyloid. They were particularly interested in how these compounds interacted and how a medication might interrupt that process.
A Needle in the Haystack:
The scientists started with gene mapping to identify which medications might reduce accumulation of amyloid and tau in the brain. They cast a wide net. More than 1,600 medications were considered. They narrowed the search to 66 FDA-approved drugs.
Here is what they did next:
“We systematically retrieved anti-AD [Alzheimer disease] clinical, in vivo [test tube] and blood-brain barrier (BBB) properties from publicly available databases for the 66 candidate drugs. Among the 66 drugs, 21 network-predicted drugs have reported clinical or pre-clinical evidence in AD, suggesting reasonable accuracy of our network proximity approach.”
They also reviewed animal research on the best candidates. Viagra topped the list.
In their own words:
“Thus, sildenafil, an FDA approved drug for erectile dysfunction, was selected as the best candidate. Vascular dementia, often occurring with AD, is one of the leading causes of age-related cognitive impairment and sildenafil has been shown to significantly improve cognition and memory in a rat model of vascular dementia. In addition, sildenafil treatment also attenuates the magnitude of the tauopathy in AD Tg2576 transgenic mice. Thus, we selected sildenafil to test the drug user’s relationship with AD outcomes using population-based observational studies.”
Test tube studies also showed that sildenafil helped neurons grow new projections and dampen production of tau.
Examining Insured Individuals and Medicare Advantage Plan Beneficiaries:
Next they analyzed insurance claims covering 7.23 million Americans.
They found that:
“…sildenafil usage was significantly associated with a decreased risk of AD.”
More specifically, people taking sildenafil were 69% less likely to get an Alzheimer diagnosis during six years of follow-up.
Will Viagra Help Prevent Dementia?
The authors were careful to note that this research does not establish cause and effect. For that, we will need randomized controlled trials in humans at risk for dementia. The cohort study described at the top of this article offers support for this concept. For real confirmation, scientists would need to conduct a randomized controlled trial.
The Cleveland Clinic investigators were very methodical in their pursuit of an old drug that might be taught a new trick. Sildenafil has “improved memory, amyloid plaque load, inflammation and neurogenesis [new neuron formation]”
The authors also point out that sildenafil:
“…increased cerebral metabolic rate of oxygen and cerebral blood flow in 12 patients with AD and decreased cerebral vascular reactivity in 8 patients with AD. Altogether, we believe that these data provide a potential mechanism of action of the protective efficacy of sildenafil in AD…”
Not The First Time Sildenafil Has Been Repurposed:
Most people do not realize this, but the FDA has approved sildenafil for both erectile dysfunction and something called pulmonary arterial hypertension. There is actually a brand of sildenafil called Revatio that “is indicated for the treatment of pulmonary arterial hypertension.”
In this condition, the blood vessels that feed the lungs are constricted, which makes it harder for blood to circulate through that organ. This can lead to heart damage. People often experience shortness of breath and fatigue. The dose of sildenafil is lower for pulmonary hypertension than the dose that is prescribed for ED.
Words of Caution:
We absolutely agree with the authors of this study that:
“The association between sildenafil use and decreased incidence of AD does not establish causality, which will require a randomized controlled trial.”
People hoping to ward off dementia should not start using sildenafil based on this preliminary research. We absolutely need well-conducted clinical trials to prove or disprove the theory. Remember, Viagra has side effects. They include
• Heartburn
• Headache
• Insomnia
• Flushing
• Muscle pain
• Shortness of breath
• Rash
• Runny nose, sinusitis
• Visual changes, loss of vision
And sildenafil can interact with many other drugs.
Nevertheless, we think some government agency or philanthropic organization should pay for a clinical trial to answer the question: Could Viagra help prevent dementia? The sooner such research is started, the better!
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