Viral infections cause a lot of mischief! One need look no further than COVID-19 to verify that there can be long-lasting complications after such illnesses. The neuroscience community has long ignored the idea that viruses might play an important role in the development of dementia. But over 40 years ago, a pathologist named Melvyn J. Ball, MD, linked herpes simplex virus (HSV) type 1 to Alzheimer dementia. A study recently published in Nature Medicine (July 25, 2024) reveals that the shingles vaccine (Shingrix) “is associated with a significantly lower risk of dementia in the 6 years post-vaccination.” That is way better than the pricey drugs the FDA has recently approved to treat Alzheimer’s disease. Maybe the experts should start considering shingles vaccines against dementia!
A VERY Short History of Vaccines:
Vaccinations are considered one of the great advances in modern medicine. Diseases like smallpox, polio, diphtheria, measles, whooping cough, influenza and tetanus used to kill hundreds of millions of people around the world.
People who survived their infection might be disabled for life. Polio victims sometimes needed leg braces or wheelchairs to get around. Those who caught smallpox were often left with disfiguring scars or blindness.
Nowadays, most of these dangerous diseases are preventable with vaccinations. Other infections, however, may have lasting consequences that scientists are just starting to recognize.
Infections That Can Cause Long-Lasting Complications:
Lyme Disease:
The bacterium Borrelia burgdorferi can cause chronic Lyme symptoms, even when an infection is treated with antibiotics. Symptoms may include fatigue, brain fog, body aches and heart damage.
ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome):
The cause of ME/CFS remains somewhat mysterious. People often complain of a flu-like illness. It may be caused by an enterovirus. Symptoms can include extreme exhaustion, brain fog, body aches, headaches, joint pain, GI problems and so much more.
Bartonellosis:
The Bartonella bacteria can cause cat scratch fever, trench fever and many long-lasting symptoms. This germ is spread by fleas, sand flies and body lice, to name just a few of the vectors. Veterinarians are especially vulnerable to bartonellosis because so many pets have fleas. Long-lasting symptoms of the disease include relapsing fever, eye problems, foot pain, anemia, fatigue, arthritis and brain fog, to name just a few.
Long COVID:
COVID-19 is the most recent example of residual symptoms brought on by an infection. It is estimated that 18 million Americans now suffer from long-lasting post-COVID conditions. Those include chronic fatigue, cardiovascular complications, neurological symptoms, brain fog and diabetes.
There are many other infectious agents that can also cause chronic symptoms. They include the polio virus, Epstein Barr virus, West Nile virus, dengue virus and many more viruses and bacteria. The old idea of one and done is long gone. Perhaps you noted that “brain fog” is a common complaint of patients who experience one of these infections.
Infections That Can Cause Long-Lasting Mischief:
Gum disease (periodontitis) is an infection of the tissues around the teeth. It has been linked to heart attacks, heart disease and strokes (Frontiers in Cardiovascular Medicine, Feb. 27, 2023).
Hard-to-treat adult-onset asthma may also be related to infection. Chlamydia pneumoniae causes sore throats, sinus infections, laryngitis and bronchitis in its acute phase. Symptoms sometimes last for several weeks.
According to the CDC, C. pneumoniae infections might also raise the risk of a person developing arthritis or atherosclerosis as well as asthma. These conditions may not show up until after the infection appears to be long gone.
A lot of people think of influenza as little more worrisome than the common cold. Now evidence from the Netherlands shows a clear link between flu infections and heart attacks (NEJM Evidence, July 2024).
Heart attacks were six times more likely to occur during the week after suffering an episode of the flu. There is evidence that vaccinating against influenza can also protect people from major adverse cardiovascular events (European Heart Journal Suppl., Feb. 14, 2023).
A New/Old Vision of Dementia:
Let me offer you a metaphor that might, or might not, be a fair representation of the origins of Alzheimer disease. Imagine a match being lit in a broom closet of a large house. If that match falls on a pile of rags, it might slowly start a smoldering fire. Over time, that fire could burn out of control. There would be a lot of smoke and eventually it would burn the house down.
Someone watching from outside might first see the smoke. Eventually that person would detect flames. Finally, the fire would become fully apparent and eventually the whole house would be demolished.
What if one of the metaphorical matches of Alzheimer’s disease is a viral infection? Trying to put out the fire by sucking up the smoke would be fruitless. The only way to prevent the brain from burning down would be to either prevent the match from lighting in the first place or putting out the fire before it could take hold.
Tens of billions of dollars have been spent creating and developing medications that eliminate beta amyloid plaque in the brain. If that sticky protein is equivalent to smoke from the fire, eliminating it would do little, if anything, to prevent the “burning” brain from continuing its downward spiral.
If, on the other hand, viruses are the matches, then vaccinating against the resulting sparks or treating with anti-viral medications might actually slow or stop the brain fire from progressing.
Which Vaccines Help Against Dementia?
Vaccines may also play a key role in preventing dementia. There is growing evidence that herpes viruses could be contributing to the development of Alzheimer disease (Journal of Alzheimer’s Disease, Feb. 13, 2024).
Several vaccinations have shown potential to reduce the likelihood of developing dementia. They include flu shots (NPJ Vaccines, March 2, 2024) and BCG vaccine used to prevent tuberculosis or treat bladder cancer (Journal of Alzheimer’s Disease, March 19, 2024). BCG stands for Bacillus Calmette-Guérin. It is a 100-year-old vaccine that was originally developed to fight TB.
Even more exciting, research suggests that people who get vaccinated against shingles (herpes zoster) lower their risk for dementia (Brain and Behavior, Feb. 2024).
This meta-analysis of five studies involving over 100,000 patients concluded:
“Our data demonstrated that patients who had herpes zoster vaccination were at a significantly lower risk of developing dementia.”
More Proof That Vaccines Prevent Dementia:
The latest study on this topic in Nature Medicine (July 25, 2024) is titled:
“The recombinant shingles vaccine is associated with lower risk of dementia”
What is a recombinant shingles vaccine? It is Shingrix from GSK. It contains glycoprotein E (gE) from the chicken pox (varicella-zoster) virus. The vaccine is over 90% effective at preventing an attack of shingles.
The investigators compared Shingrix (FDA approved in 2017) to an older shingles vaccine (Zostavax) that was approved in 2006.
People who received the more effective vaccine
“…were at a lower risk of dementia in the next 6 years…translating into 17% more time lived diagnosis-free, or 164 additional diagnosis-free days among those affected.”
That isn’t to say the older Zostavax vaccine was ineffective, though. The meta-analysis of five studies described above (Brain and Behavior, Feb. 2024) concludes that all shingles vaccinations are associated with a lower risk of dementia.
It also appears that all vaccinations may reduce the risk of developing dementia. That is the conclusion of an article published in the Journal of Alzheimer’s Disease (Pre-press, Aug. 7, 2023):
“The Impact of Routine Vaccinations on Alzheimer’s Disease Risk in Persons 65 Years and Older”
They reviewed 16 million medical records from an insurance claims database. About 1.6 million senior citizens were followed for more than eight years. Those who were vaccinated for tetanus and diphtheria were 30% less likely to receive a diagnosis of Alzheimer disease. Shingles vaccinations (herpes zoster or HZ shots) lowered the risk by 25%. Pneumonia vaccines also reduced the likelihood of developing dementia by about 27%.
For our sophisticated readers, these were relative risk reductions. Absolute risk dropped by 2 to 3 percent.
The authors concluded:
“Using a retrospective cohort study, we found that there were significant decreases in AD for patients 65 and older who received a Tdap/Td [tetanus and diphtheria] vaccination (30%), an HZ [herpes zoster] vaccination (25%), or a pneumococcal vaccination (27%) versus separate unvaccinated groups over an 8-year period. Our main analysis results are consistent with other studies of these three vaccines suggesting a possible preventative effect on dementia.”
The Shingrix vaccine actually produced better results. People who received at least one dose of this shingles vaccine reduced their likelihood of developing Alzheimer disease by 73%.
Shingles Vaccines Against Dementia:
An earlier study from Wales also suggested that the shingles vaccine could reduce the risk of developing dementia (MedRxiv, May 25, 2023). First, a word of caution. This study has been published as a “preprint.” That means it has not yet been certified by peer review. That said, the idea of using shingles vaccines against dementia is extraordinary. There is also evidence to suggest that influenza vaccines can prevent heart attacks and deaths from cardiovascular disease.
The Accidental Experiment of Vaccines Against Dementia:
The authors of this preprint introduce their article by describing disappointments with available treatments against dementia.
They write:
“Despite decades of large-scale investments into research on dementia, including hundreds of failed phase 2 and phase 3 clinical trials of pharmaceutical agents for the prevention or treatment of dementia, the root causes of dementia still remain largely unclear. Recently, there has been growing scientific recognition that viruses may play a role in the pathogenesis of dementia. Different lines of evidence, including the observation that herpesviruses can seed β-amyloid – a hallmark of Alzheimer’s dementia – in mice, suggest a possible role for herpesviruses in particular in the pathogenesis of dementia.”
These investigators analyzed data from Wales to see whether the shingles vaccine might prevent the cognitive decline of dementia.
In Wales, people born before Sept. 2, 1933 were ineligible for the Zostavax vaccination to prevent shingles, whereas those born on Sept. 2, 1933 and thereafter were eligible. The researchers established that there were no other important differences between the older people in their study population.
During seven years of follow-up, people who had received the herpes zoster vaccine were 20 percent less likely to develop dementia. That was the relative risk. The absolute risk difference was 3.5 percent, still significant.
In Their Own Words:
If you didn’t completely understand our interpretation of the study, here is how the authors describe shingles vaccines against dementia:
“This study found that the zoster vaccine reduced the probability of a new dementia diagnosis by approximately one fifth over a seven-year follow-up period. By taking advantage of the fact that the unique way in which the zoster vaccine was rolled out in Wales constitutes a natural experiment, and meticulously ruling out each possible remaining source of bias, our study provides causal rather than associational evidence.”
They go on to add:
“Our rigorous causal approach allows for the conclusion that herpes zoster vaccination is very likely an effective means of preventing or delaying the onset of dementia. Our substantial effect sizes, combined with the relatively low cost of the zoster vaccine, imply that the zoster vaccine is both far more effective as well as cost-effective in preventing or delaying dementia than existing pharmaceutical interventions.”
Put another way, this study, which offered a sort of natural randomization, suggests that shingles vaccines against dementia are not a far-fetched concept.
We should point out that the Zostavax vaccine considered in this study is less effective than the current Shingrix vaccination. The latest research cited at the top of the article suggests that Shingrix vaccines against dementia are even better at reducing the risk for cognitive decline.
Influenza Vaccines vs. Heart Attacks:
We have been fairly critical about flu shots. That’s because they are not as effective as many people think. Here is just one of our more recent rants about influenza vaccines.
Despite our general disappointment with flu shot effectiveness, these jabs have an added bonus that most people are unaware of.
A recent meta-analysis of randomized vaccine trials reveals that (The American Journal of Medicine, May, 2023):
“Influenza vaccine is a cheap and effective intervention to reduce the risk for all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome among coronary artery disease patients, especially in those with acute coronary syndrome.”
What They Discovered About Flu Shots:
The authors reviewed five clinical trials involving over 4,000 patients with coronary artery disease. Some had severe heart disease and were heart attacks waiting to happen.
People with heart disease who got flu shots reduced their cardiovascular mortality by 46%. That is impressive. The worse the heart disease, the greater the benefit. In other words, people with symptoms of severe heart disease or an impending heart attack got the greatest benefit.
What Are Some Symptoms of Acute Coronary Syndrome?
Significant chest pain including tightness or pressure
Breathing problems such as shortness of breath
Jaw pain or discomfort running down the arm
Faintness or dizziness
Nausea and sweating
How Does an Influenza Vaccine Work Against Heart Disease?
We cannot give you an absolute answer to this question. What we have learned about influenza and COVID-19 is that viral infections can trigger inflammation throughout the body, including the heart. If this occurs within the walls of coronary arteries, it may precipitate plaque rupture. That in turn could start a cascade of events leading to a heart attack.
There is also a growing belief that flu viruses could accelerate atherosclerosis. The idea that an infection could promote heart disease is rather radical, but not that surprising. We have evidence that SARS-CoV-2 can also cause serious cardiovascular complications (Biochemical Pharmacology, Aug. 2020; Immunity, Inflammation and Disease, March, 2023).
Final Words:
The idea that viruses such as influenza or herpes zoster might contribute to long-lasting cardiovascular or neurological disorders is controversial. However, if vaccines could prevent heart attacks or delay the development of dementia, they might revolutionize our approaches to these hard-to-combat conditions.
There is a growing anti-vax movement in the United States. That alarms me. I am not objective about this issue. That’s because I had polio as a child. This was before there were polio vaccines. I also caught whooping cough long before there was a pertussis vaccine. Both diseases could have been fatal.
I still suffer from PTSD because of my days in a polio ward as a child. Children were dying all around me. Being restrained in traction when you are a little kid is a life-altering situation.
I am not advocating that everyone rush out and get a shingles vaccine or an annual flu shot. But I would hope that the anti-vax movement will not discourage people from considering the unexpected health benefits of such vaccinations.
Final-Final Words:
On this week’s nationally syndicated People’s Pharmacy radio show we talk with Bodil Weidung, PhD, of Uppsala University, Sweden and Pascal Geldsetzer, MD, of Stanford University Medicine. Both have been involved in research indicating that herpes viruses could play an important role in the pathogenesis of Alzheimer’s disease. They will describe the nature of their different studies and why neuroscientists need to start thinking creatively about ways to overcome dementia.
You can listen live at 7:00 am on Saturday, August 3, 2024 by streaming the show from WUNC-FM. It is our host NPR station. There are other NPR stations that carry our radio show. Here is a link to find out where else we are heard. If your local NPR station does not yet carry The People’s Pharmacy, why not contact the program director and encourage your station to join us?
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