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 new study in the Journal of Alzheimer’s Disease (March 19, 2024) is titled “Sildenafil as a Candidate Drug for Alzheimer’s Disease.”

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.

We have written a lot lately about the disappointing results from anti-amyloid drugs. The FDA approved two medication in the last few years. One, Aduhelm, was recently discontinued. You can read about this hot mess at this link. The other, lecanemab (Leqembi) is now available. The annual price is listed at $26,500, but that is not the full story. 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 (around $25 for 30 pills with a coupon) and 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.

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. Although most of them have targeted amyloid, the only medication that was approved works on a different mechanism.

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 have 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 recently 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 recent 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.

Can You Prevent Alzheimer’s Disease?

While we wait for the courts to decide the fate of Prevagen and drug companies to come up with better medicines, what can people do to protect their brains? Probably the best results will come from efforts at prevention. 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 recent interview with a leading neuroscientist of interest. In it he describes his recommendations for preventing dementia. It is the last interview of the show.