Is It Possible to Prevent Alzheimer’s Disease with Viagra (Sildenafil)?

 I'm not waiting for exact proof, I do Cialis instead.

Check out the research for yourself, when I asked my doctor he pooh-poohed the idea, saying it was to early to tell. I'm ignoring him.

• Erectile Dysfunction Drugs (5 posts to February 2024) 

The latest here:

Is It Possible to Prevent Alzheimer’s Disease with Viagra (Sildenafil)?

The descent into dementia is horrific. It can creep up gradually, robbing people of their personalities as well as their memories. Friends, family and co-workers have a hard time dealing with the forgetfulness and cognitive dysfunction. Family members often struggle to help their loved one stay safely at home, but frequently that becomes an overwhelming task. For those who have had to deal with dementia, the question we get most often is, “How can I prevent Alzheimer’s disease myself?” A study in the Journal of Alzheimer’s Disease (March 19, 2024) was titled “Sildenafil as a Candidate Drug for Alzheimer’s Disease.”

In case you don’t recognize the drug sildenafil, it is the generic name for Viagra! That’s right, the medication that the FDA approved for erectile dysfunction in 1998.

The Pharmaceutical Industry Dropped the Ball:

With nearly 7 million people suffering from Alzheimer disease it should come as no surprise to learn that drug companies have been trying hard to come up with effective treatments. It would be a billion-dollar bonanza for any drug company if it had a medication that actually improved memory and/or helped keep people out of nursing homes. Families would be ecstatic if there were ever such a breakthrough.

A nursing home can cost any where from $80,000 to $120,000 a year. Many people would be willing to spend their life savings to stay out of such a facility. If there were a medicine that could accomplish that, a pharmaceutical manufacturer could charge $100,000 a year or more. Do the math. That would equal $500,000,000,000. If you lost count of the zeroes, that is $500 billion, which is a mind-boggling amount of money.

Drug companies are thrilled if a medication earns a billion dollars in a single year. A $5 billion drug is a blockbuster. A $500 billion dollar drug would bankrupt insurance companies and families. If it worked, though, people would likely pay, just as they now are paying over $100,000 a year for some cancer drugs.

The Anti-Amyloid Drug Disappointment

We have written a lot about the disappointing results from anti-amyloid drugs. The FDA approved three medications in recent years. One, Aduhelm, was discontinued. You can read about this hot mess at this link. The others include donanemab (Kisunla) and lecanemab (Leqembi). Estimating price is tricky, but we have seen numbers like $32,000 for Kisunla and $26,500. That is not the full story, though. CBS News did an in-depth report (Aug. 1, 2023) titled: “The real costs of the new Alzheimer’s drug, Leqembi — and why taxpayers will foot much of the bill:”

“In addition to the company’s $26,500 annual price tag for the drug, treatment could cost U.S. taxpayers $82,500 per patient per year, on average, for genetic tests and frequent brain scans, safety monitoring, and other care, according to estimates from the Institute for Clinical and Economic Review, or ICER.”

“To qualify for Leqembi, patients must undergo a PET scan that looks for amyloid plaques, the protein clumps that clog the brains of many Alzheimer’s patients. About 1 in 5 patients who took Leqembi in the major clinical test of the drug developed brain hemorrhaging or swelling, a risk that requires those taking the drug to undergo frequent medical checkups and brain scans called MRIs.”

More about anti-amyloid drugs shortly.

What About Generic Sildenafil (Viagra) To Prevent Alzheimer’s Disease?

The pharmaceutical industry and a lot of neuroscientists don’t seem terribly excited about the paper in the Journal of Alzheimer’s Disease (JAD) (March 19, 2024) involving Viagra. Maybe that’s because sildenafil is relatively inexpensive (anywhere from $15 to $30 for 30 pills with a coupon). It does not fit the classic anti-amyloid model of AD that has prevailed for so long.

The JAD study was ambitious. It suggests that the ED drug Viagra might reduce the risk of developing Alzheimer disease. Researchers at the Cleveland Clinic identified genes involved in the development of amyloid plaques and tau tangles in the brain. These are distinctive markers of dementia. Analysis showed that sildenafil (the generic name for Viagra) had the potential to interact with these genes in a positive way.

Then the investigators evaluated two large patient databases of insurance claims. People taking sildenafil were substantially less likely to be diagnosed with Alzheimer disease than those taking the blood pressure pill spironolactone. Test tube research had previously shown that the drug could improve neuron growth and reduce the accumulation of toxic tau.

The authors describe their research in somewhat technical, but understandable language:

“Sildenafil is a selective PDE5 inhibitor and PDEs are broadly expressed in human brain. Recent studies have shown that sildenafil has beneficial effects in various preclinical models of AD by modulating neuronal plasticity, reducing tau phosphorylation, improving cognitive impairment, decreasing amyloid betaplaque accumulation, and enhancing the level of BDNF [brain-derived neurotrophic factor]. Our previous study found that sildenafil increased neurite growth and decreased phospho-tau (pTau181) in AD patient iPSC-derived neurons, mechanistically supporting its potential beneficial effect in AD.

“Furthermore, two pilot trials demonstrated beneficial effects of sildenafil in treatment of AD, where a single dosage of 50 mg sildenafil reduced spontaneous neural activity in the right hippocampus in 10 patients; and increased the cerebral metabolic rate of oxygen and cerebral blood flow in 12 patients; and decreased cerebral vascular reactivity in 8 patients.

“Recent observations involving data from over 30 million insured members validates the association between sildenafil use and reduced risk of AD. This study showed that sildenafil could reduce the risk of AD by 60% which in consonant with our findings.”

We grant you that this is pretty technical. The authors sum up their research by suggesting that:

“…sildenafil can be a potential repurposable drug for the treatment of AD and warrants further testing in more functional models and randomized controlled clinical trials.”

Sadly, we do not expect any drug company to take them up on this suggestion. Sidenafil is incredibly cheap compared to anti-amyloid drugs. And drug companies cannot make money on medications that have lost their patents. It remains to be seen whether other funding groups will sponsor randomized controlled trials to demonstrate whether sildenafil or other ED drugs that inhibit PDE5 could be truly effective against Alzheimer’s disease.

A Recent Visitor to This Website Wanted a 2026 Update:

We received this question from a visitor to www.PeoplesPharmacy.com:

Q. A few years ago you wrote about a Viagra study. It looked really promising, because it showed a 30 to 54 percent reduction in Alzheimer’s disease from a drug that isn’t even taken daily! I really hope that researchers will follow up with a clinical trial.

Meanwhile, men could try taking Viagra. But what about women?

A. Back in 2024 researchers reported preliminary results suggesting that sildenafil (Viagra) might help protect against Alzheimer’s disease (AD). One report noted that sildenafil reduced phosphorylation of tau, one of the important risk factors neurologists note for this dementia (Journal of Alzheimer’s Disease, 2024). In addition, the investigators analyzed medical records in two large databases and found, as you wrote, a significant reduction in AD.

Another study also relied on medical records and found that men taking sildenafil or a similar drug were also less likely to develop AD over five years (Neurology, Feb. 7, 2024).

 The researchers concluded:

“…a randomized controlled trial including both sexes and exploring various PDE5I [sildenafil-like drugs] doses would be beneficial to confirm the association between PDE5I and AD.”

So far as we can tell, only one such study has been published (Journal of Prevention of Alzheimer’s Disease, Nov. 2025). The study of mirodenafil was small and did not show benefit in people who had already been diagnosed with AD. We are still waiting for a large, well-controlled, long-term trial.

The Anti-Amyloid Bet: A Big Disappointment

The results of anti-amyloid drugs have been disappointing at best. One experimental treatment that struck out was solanezumab. This monoclonal antibody (“mab”) was designed to harness the brain’s immune system to attack and remove amyloid.

Researchers know that beta-amyloid protein clumps together to form plaques in the brains of people with Alzheimer disease. They made the assumption that getting rid of these plaques would protect the brain against dementia. Unfortunately, although solanezumab was quite good at reducing brain levels of amyloid, it was no better than placebo at slowing cognitive decline.

A Familiar Failure:

This is not the first time an anti-amyloid drug has produced disappointing results. Since 2000, the pharmaceutical industry has tested more than 200 compounds.

Some investigators are beginning to question the amyloid theory of Alzheimer disease. There is even a suggestion that amyloid might play a protective role when the brain is under attack by pathogens. That is because it seems to have antimicrobial activity (Molecular Pharmaceutics, April 2012; Biological Chemistry, July 2012).

The Prevagen Promise:

Prevagen has been widely advertised on television as a “breakthrough” that is “clinically shown to improve short term memory.” The active ingredient, apoaequorin, was originally derived from a protein in jellyfish.

The Federal Trade Commission and the New York Attorney General charged the maker of this dietary supplement with “making false and unsubstantiated claims that the product improves memory, provides cognitive benefits, and is ‘clinically shown’ to work.”

The company, Quincy Bioscience, “vehemently disagrees with these allegations…” and maintains that “Prevagen improves memory and supports healthy brain function.”

ConsumerLab.com wrote an article titled: “Does Prevagen really improve memory?”

“According to the Prevagen website, ‘Prevagen is an over-the-counter supplement for healthy brain function and memory improvement.” A disclaimer indicates that these statements are “Based on a clinical study of subgroups of individuals who were cognitively normal or mildly impaired.’ Its package also claims that Prevagen supports ‘healthy brain function, sharper mind, and clearer thinking.’

“However, as discussed below, there is little evidence that Prevagen (from Quincy Bioscience) provides any meaningful benefit in terms of memory improvement, and the extent of potential improvement appears to be minimal. Due to actions by the FTC, the marketing claims for Prevagen have been scaled back from earlier claims that it treats conditions such as head injuries and Alzheimer’s disease.”

ConsumerLab.com goes on to discuss litigation:

“In March 2024, a jury verdict for another case brought against Prevagen by the state of New York (Federal Trade Commission et al v. Quincy Bioscience Holding Company, Inc. et al, Case #1:17-cv-00124) found that all eight statements challenged in the suit, including “Prevagen improves memory” and “Prevagen improves memory within 90 days,” lacked support by “competent and reliable scientific evidence.” Furthermore, the jury found two of the statements to be deceptive or materially misleading: These were that “Prevagen reduces memory problems associated with aging” and “Prevagen is clinically shown to reduce memory problems associated with aging.”

You can read the full ConsumerLab.com report at this link.

These days, Prevagen commercials are very careful about the language that is used. What you will see and hear are the words:

“Prevagen For Your Brain“

Another 2026 commercial asks: “What do you do to take care of your brain?” 

It recommends:

“Daily Brain Care” with Prevagen because “It’s made for your brain.”

The asterisk on the screen states: “not evaluated by the FDA. Not intended to treat/prevent disease.”

Can You Prevent Alzheimer’s Disease?

A Finnish study recruited older people with average or below-average cognitive scores. It demonstrated through a randomized trial of improvements in diet, exercise, cognitive training, blood pressure and cholesterol control that these could lead to significant improvement in cognitive scores (Lancet, June 6, 2015).

A Researcher Who Claims to Have Reversed Dementia:

Readers who would like to learn more about how a variety of preventive strategies may wish to listen to our interview with Dale Bredesen, MD. It can be found at PeoplesPharmacy.com. In it, he describes his multifactorial interventions to reverse dementia.

You may also find a more recent interview with Dr. Bredesen of interest as well:

Show 1412: Beyond Amyloid: The Science That Could Change the Course of Alzheimer Disease
A personalized approach considering multiple factors may be helpful for changing the course of Alzheimer disease.

You can listen to the podcast on Apple Podcasts at this link or on Spotify.

We would be grateful if you would share this article with someone you think might find it helpful.

Citations

• Greeley, D., et al, "A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhibitor, in patients with mild-to-moderate Alzheimer's disease," Journal of Prevention of Alzheimer's Disease, Nov. 2025, doi: 10.1016/j.tjpad.2025.100337
• Gohel, D., et al, " Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons," Journal of Alzheimer's Disease, March 19, 2024, doi: 10.3233/JAD-231391

Cialis is an erectile dysfunction drug. Could it also help you live longer?

 Since the stroke already has me in the high risk category of cardiovascular disease I'm already taking Cialis daily. Better blood flow to the brain. Hasn't your doctor immediately put you on this to save some neurons from the neuronal cascade of death in the first week? 

And this:

Erectile Dysfunction Drugs May Protect Against Alzheimer’s August 2024

Cialis is an erectile dysfunction drug. Could it also help you live longer?

Tadalafil – better known by its brand name Cialis – is one of the most commonly prescribed drugs for erectile dysfunction.

But in some biohacking and wellness circles, it's increasingly being repurposed for an entirely different reason.

Online clinics and influential figures are promoting it as a kind of all-purpose longevity drug – delivering benefits for the cardiovascular system, brain and even athletic performance.

The drugs aren't approved for preventing heart attack and stroke, let alone for extending life.

However, the enthusiasm does reflect growing interest among some experts in the field of cardiology and men's health that tadalafil and other drugs in its class could have a legitimate role in preventive health.

"It's a serious area of discussion," says Dr. Robert Kloner, director of cardiovascular research at the Huntington Medical Research Institutes and a professor at the University of Southern California. 

"Cardiovascular disease remains the number one killer – and we have these drugs that may have a potential benefit, but we have to learn a lot more."

The buzz of longevity

Tadalafil belongs to the same class of drugs as sildenafil, i.e., Viagra – with the primary difference being that its effect lasts considerably longer.

While both have been on the market for decades, a handful of large studies, many of them published in recent years, have shown that men taking the drug fare better: They have lower rates of cardiovascular disease and death, and, in some cases, are less likely to develop dementia.

The major studies in this area are observational – and retrospective – meaning they can only show associations, not that tadalafil was the definitive cause.

Want the latest stories on the science of healthy living? Subscribe to NPR's Health newsletter.

But the findings are remarkably "consistent" across the literature, says Kloner, whose lab has studied these medications extensively. "It's a very interesting signal."

The research has surfaced in the online longevity conversation, and prominent voices – from Stanford neuroscientist and podcaster Andrew Huberman to the immortality-seeking tech mogul Bryan Johnson – have talked up the idea of taking tadalafil for more than sex.

Even some women are getting on board.

"It seemed very harmless," says Kristi Sawicki, who holds a doctorate in molecular oncology and has built a following on social media around longevity.

"If anything it's going to help blood flow and that can be beneficial to our brain and our heart," she told NPR.

Sawicki started taking tadalafil about a year ago.

It was one of the offerings in the online telehealth clinic she used for her GLP-1 prescription. That prompted her to dig into the research herself.

"It's a very well-understood mechanism," she says.

As someone with a family history of heart disease, she saw taking tadalafil as "low-hanging fruit" for cardiovascular health – and has also noticed other benefits, like a better pump in the gym.

The studies

While mostly used for erectile dysfunction, both tadalafil and sildenafil are approved for treating a rare form of high blood pressure affecting the lungs. Tadalafil can also be prescribed for symptoms of an enlarged prostate in men.

In essence, these medications – known as PDE-5 inhibitors – work by preventing the breakdown of a signaling molecule, which in turn helps relax smooth muscle cells and dilate blood vessels.

This not only improves blood flow in one particular region but also relaxes and widens blood vessels throughout the body, Kloner says.

Sildenafil – approved in the late '90s – was famously developed as a drug to treat chest pain caused by poor blood flow to the heart, until its "side effects" were recognized and drug makers changed course.

There's evidence – mostly from small trials in humans – that PDE-5 inhibitors like tadalafil may benefit blood-vessels. Plus, lab and animal research have suggested these drugs can also have anti-inflammatory effects.

The studies drawing on medical records of men who were prescribed these drugs, primarily for erectile dysfunction, have shown sizable effects.

For example, an analysis by Kloner of more than 8,000 men taking tadalafil found they had a 55% lower rate of dying from cardiovascular causes and a 44% lower rate of overall mortality during the study period.

Another study – this based on more than half a million patients – showed a 32% lower risk of dementia among those taking tadalafil, along with improved mortality.

"We were particularly fascinated by the dementia piece," says Dr. Dietrich Jehle, chair of emergency medicine at the University of Texas Medical Branch in Galveston and lead author of the analysis, noting that data from the U.K. has also indicated a lower risk of Alzheimer's disease.

Researchers like Kloner and Jehle emphasize that without prospective studies – ideally randomized trials – these findings need to be read with caution. There could be unknown factors that influence why men who seek out medications for erectile dysfunction are less likely to die and develop certain diseases. Kloner also acknowledges the drugs are not as well studied in women.

The problem, he says, is that pharmaceutical companies aren't incentivized to run these costly studies because generic versions of the drugs are already available.

"It's not something that cardiologists are routinely recommending, I'll tell you that," Kloner says. "But these drugs in general are very safe."

The online marketplace

Much of the current marketing around tadalafil comes from direct-to-consumer online clinics, where it's often advertised alongside other trendy wellness and longevity therapies.

For example, AgelessRx – a company that Sawicki promotes in her online content – sells a monthly $70 prescription of low dose tadalafil for longevity purposes.

In an interview with NPR, the company's medical director, Dr. Jenell Decker said she felt the data were strong enough to warrant offering it to both men and women over 40.

"In longevity, that's what you have to do with a lot of things, you have to infer," she says, "because if you wait until a person is already showing symptoms, you're already behind."

But some experts are troubled by this off-label use of the medication, without better data in humans.

"Absence of evidence of harms doesn't mean there isn't harm," says Dr. Steve Nissen, chief academic officer of the Cleveland Clinic Heart, Vascular & Thoracic Institute. "In the absence of randomized controlled trial data, it's pretty hard to justify."

Expert panel evaluating the merits

There are signs tadalafil could be gaining wider acceptance outside of the online wellness and optimization world.

The topic came up recently during the latest meeting of an influential medical group, known as the Princeton Consensus Panel, which focuses on men's sexual function and cardiovascular health.

The group of medical experts – which included Kloner and other preventive cardiologists – arrived at consensus language that low dose tadalafil is "appropriate" for a subset of men who are at elevated risk of developing cardiovascular disease due to the build up of plaque in their arteries, according to Dr. Martin Miner, who co-chaired the June conference. (Their formal recommendations are not yet published.)

In an email to NPR, Miner acknowledged some were "hesitant" to endorse this broader use of tadalafil because there were no randomized controlled trials, but ultimately decided to do so, based on the existing observational research.

"This is not for all men," says Miner, who directs the Men's Health Center at Brown University in Providence, R.I., though he does prescribe it for many of his patients who're at higher risk of cardiovascular disease.

"I believe men need all the help we can give them due to the longevity gap in this country," he added.

Erectile Dysfunction Drugs May Protect Against Alzheimer’s

 Your competent? doctor has a lot of analysis to do on this. Ask them how often you should be taking the drug; daily, weekly?

 Have fun asking your doctor this question.

Maybe because of these:

Viagra Shows Promise in Boosting Brain Blood Flow for Dementia Prevention

Or this:New Data Support Viagra for Alzheimer’s Prevention

Or this:Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons

Or maybe this: FDA Approves 'Female Viagra' Amid Cheers and Jeers August 2015.

But this for the negative view: Does Viagra really help prevent Alzheimer’s? Not so fast

Can Women Benefit From Viagra?

The latest here:

Erectile Dysfunction Drugs May Protect Against Alzheimer’s

Summary: A new study suggests a potential association between erectile dysfunction (ED) drugs and a reduced risk of developing Alzheimer’s disease, though it does not establish causality.

The study tracked 269,725 men over five years, finding those prescribed ED medication had an 18% lower risk of Alzheimer’s after adjusting for other factors. While the drugs, originally developed for high blood pressure, show promise in preventing Alzheimer’s, further research is needed to confirm these findings and explore the mechanisms behind the association.

The study underscores the urgent need for new treatments to delay or prevent Alzheimer’s disease.

Key Facts:

1. Participants taking ED drugs exhibited an 8.1 per 10,000 person-years rate of Alzheimer’s development, compared to a 9.7 rate among those not on the medication.
2. After adjustments, ED drug users had an 18% reduced risk of Alzheimer’s disease compared to non-users.
3. The study suggests a need for more research, including randomized controlled trials, to verify these results and consider their applicability to women.

Source: AAN

The drugs used to treat erectile dysfunction may also be associated with a reduced risk of Alzheimer’s disease, according to a study published in the February 7, 2024, online issue of Neurology.

The study does not prove that erectile dysfunction drugs reduce the risk of Alzheimer’s disease. It only shows an association.

Erectile dysfunction drugs, which work by dilating blood vessels to allow more blood to flow through, were first developed to treat high blood pressure. A new study suggests that the drugs may be tied to a reduced risk of Alzheimer’s disease.

The association was strongest in those who were issued the most prescriptions over the study period. Credit: Neuroscience News

“Although we’re making progress with the new treatments for Alzheimer’s disease that work to clear amyloid plaques in the brain for people with early stages of the disease, we desperately need treatments that can prevent or delay the development of Alzheimer’s disease,” said study author Ruth Brauer, PhD, of the University College London in the United Kingdom.

“These results are encouraging and warrant further research.”

The study involved 269,725 male participants with an average age of 59 who were newly diagnosed with erectile dysfunction. Participants did not have any memory or thinking problems at the start of the study.

They were then followed for an average of five years. The study compared the 55% of the participants who had prescriptions for erectile dysfunction drugs to the 45% who did not have prescriptions.

During the study, 1,119 people developed Alzheimer’s disease.

Among the participants taking erectile dysfunction drugs, 749 developed Alzheimer’s disease, which corresponds to a rate of 8.1 cases per 10,000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study.

Among those who did not take the drugs, 370 developed Alzheimer’s disease, which corresponds to a rate of 9.7 cases per 10,000 person-years.

Once researchers adjusted for other factors that could affect the rate of Alzheimer’s disease, such as age, smoking status and alcohol consumption, they found that people who took erectile dysfunction drugs were 18% less likely to develop Alzheimer’s than people who did not take the drugs.

The association was strongest in those who were issued the most prescriptions over the study period.

“More research is needed to confirm these findings, learn more about the potential benefits and mechanisms of these drugs and look into the optimal dosage,” Brauer said. “A randomized, controlled trial with both male and female participants is warranted to determine whether these findings would apply to women as well.”

The study was based on prescription records. A limitation of the study is that researchers did not have information on whether participants actually filled the prescriptions and used the drugs.  

About this neuropharmacology and Alzheimer’s disease research news

Author: Renee Tessman
Source: AAN
Contact: Renee Tessman – AAN
Image: The image is credited to Neuroscience News

Original Research: The findings will appear in Neurolog

New Data Support Viagra for Alzheimer’s Prevention

 

But is it the drug or the amount of sex they are having? An easy piece of research to accomplish; WHOM will do that? What about for women?

Sex linked to better brain power in older age

 My doctor said it wasn't proven enough to do this.

But this for the negative view: Does Viagra really help prevent Alzheimer’s? Not so fast

The latest here:

New Data Support Viagra for Alzheimer’s Prevention

A new study provides more evidence that sildenafil (Viagra) which is used to treat erectile dysfunction (ED) may help protect against Alzheimer's disease (AD).

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in AD among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

"Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer's, which is in great need of new therapies," Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

"We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil's potential against this devastating neurological disease," Cheng noted. 

The study was published online on March 1, 2024, in the Journal of Alzheimer's Disease. 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of AD relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of AD in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of AD in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on AD risk, as previously reported by Medscape Medical News.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced AD risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD.

"We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer's disease," Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Cheng had no relevant disclosures.

Sildenafil(Viagra) as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons

 

But is it the drug or the amount of sex they are having? An easy piece of research to accomplish; WHOM will do that?

Sex linked to better brain power in older age

 My doctor said it wasn't proven enough to do this.

But this for the negative view: Does Viagra really help prevent Alzheimer’s? Not so fast

The latest here:

Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons

Article type: Research Article

Authors: Gohel, Dhruv^{a; 1} | Zhang, Pengyue^{b; 1} | Gupta, Amit Kumar^{a; 1} | Li, Yichen^a | Chiang, Chien-Wei^c | Li, Lang^c | Hou, Yuan^a | Pieper, Andrew A.^{d; e; f; g; h} | Cummings, Jeffreyⁱ | Cheng, Feixiong^{a; j; k; *}

Affiliations: [a] Genomic Medicine Institute,Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA | [b] Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA | [c] Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA | [d] Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA | [e] Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA | [f] Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA | [g] Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA | [h] Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH, USA | [i] Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA | [j] Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA | [k] Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

Correspondence: [*] Correspondence to: Feixiong Cheng, PhD, Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Tel.: +1 216 4447654; Fax: +1 216 6361609; E-mail: chengf@ccf.org.

Note: [1] These authors contributed equally to this work.

Abstract: 

 Background: 

Alzheimer’s disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. Objective: To investigate the potential therapeutic benefit of sildenafil on AD. 

Methods: 

We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil’s mechanism-of-action. 

Results:

We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32– 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49– 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. 

Conclusions:

These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.

Keywords: KeywordsAlzheimer’s disease, induced pluripotent stem cells, phosphodiesterase-5 (PDE5), real-world patient data, RNA-sequencing, sildenafil, tau phosphorylation

DOI: 10.3233/JAD-231391

Journal: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2024

Accepted 18 January 2024

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Published: 01 March 2024

Price: EUR 27.50