A Shot in the Arm for the Brain

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By Mary Carpenter

THE RECENT proposal to put Covid vaccinations on a regular annual schedule has raised new questions—specifically about the future of Covid vaccines but also about vaccinations in general. While repeat Covid vaccines without a sufficient several-month interval between shots could reduce the impact of each shot, all currently recommended vaccines not only confer disease protection but might also be good for brain health.

“All types of vaccinations were associated with a trend toward reduced dementia risk,” according to a multicenter study by Chinese researchers. Comparing dementia risk in vaccinated versus unvaccinated populations in 17 studies (altogether 1,857,134 participants), their analysis found vaccinations associated with a 35% lower dementia risk.

“Routine adult vaccination… may be an effective strategy for dementia prevention,” write the Chinese researchers. “A growing body of research suggests that the immune system and infections play an important role in the development of dementia: bacterial, fungal and viral infections may cause neurotoxic inflammation and oxidative stress in the brain, which can lead to neurodegeneration.”

“People who received at least one influenza vaccine were 40% less likely than their non-vaccinated peers to develop Alzheimer’s disease over the course of four years,” report neurologists Avram Bukhbinder, now at Mass General, and Paul Schultz at University of Texas, Houston—who looked at the effects of flu vaccination on a large nationwide sample of adults age 65 and older. “The strength of this protective effect increased with the number of years that a person received an annual flu vaccine.”

“Vaccinations against flu, pneumonia and shingles appear to offer protection against Alzheimer’s and Parkinson’s diseases, the most frequent forms of age-related neurodegeneration,” according to radiation oncologist Steven Lehrer at Mt. Sinai in New York.  Other vaccines associated with “significant” reduced dementia risk by the Chinese researchers: rabies, tdap (tetanus, diphtheria and pertussis) and hepatitis B.

Vaccines may help reduce the risk of dementia by preventing infectious diseases that create system-wide inflammation. But that can’t be the whole story, because while different vaccines have varying efficacies against the relevant pathogens, Lehrer writes, “significant reductions in dementia risk can be observed after almost all types of vaccination.”

“Protection against bacterial and viral infection is beneficial to the brain since these infections may activate dormant herpes simplex type 1 and herpes zoster virus,” he suggests. Another theory involves off-target or non-specific effects (NSEs) of vaccinations, for example, training the body’s immune system to prevent pathogens from entering the brain and thus reducing the risk of dementia caused by chronic and abnormal neuroinflammation.

One “unanswered question: are the AD-risk-reducing effects of flu, pneumonia, and shingles vaccinations cumulative?” asks Lehrer. And one caveat noted by the Chinese researchers: Although most vaccine studies control for demographics, comorbidities and medication use, the brain-protection effect of vaccination might reflect “the different health characteristics and lifestyles between vaccinated and unvaccinated populations, such as better knowledge of disease prevention, higher education and income, and greater social support.”

The only seasonal vaccine currently recommended by the CDC is for influenza. In addition, adults 50 and older should receive the shingles vaccine, and those 65 and older should get vaccine protection against pneumonia. Adults who did not receive the pertussis vaccine as an adolescent should receive one Tdap vaccine, and all adults should get Td (tetanus and diphtheria) or Tdap every ten years.

For chickenpox, likely exposure to the virus for anyone born before approval of the varicella vaccine in 1995 should provide immunity. And the recommendation for vaccination against hepatitis B covers ages 19 through 59, as well as those 60 and older with risk factors or who choose to get the vaccine.

For the proposed annual Covid vaccination, too many questions about the virus remain unanswered, according to the NBC report on the FDA advisory committee’s review. Because Covid has failed to settle into a predictable seasonal pattern like that of the flu, for example, it could be hard to determine when to schedule such a vaccine. Said New England Journal of Medicine Editor-in-Chief Eric Rubin, “The virus may mutate multiple times a year or it may not.”

Boosting every six months provided “very strong suppression” of infection, according to an analysis by researchers at the University of North Carolina at Charlotte and Yale University. In their six-year projection, one in 10 people who received updated boosters every six months would contract Covid —compared to three out of 10 of those who received an annual shot, and nine out of 10 among those who didn’t get a booster at all.

“The durability question “is a big one,” University of Toronto immunologist Jennifer Gommerman told Science —whether an annual Covid booster could offer enough protection for a whole year, and how much that might vary by a person’s age. Experts worry that policy decisions might outpace the data.

For now, confusion over how well boosters work may be one reason for low uptake of the newer bivalent shot—by only 40% of people 65 and older, the most vulnerable population. Many mistakenly believe they are protected against infection or severe disease because of previous vaccination or infection, while others appear wary of the new-technology messenger-RNA vaccines made by Pfizer and Moderna—or are reluctant to undergo the side effects, such as flu-like symptoms that can persist for several days.

The bivalent booster has, in new research from this January, proved as effective against the latest Omicron viral sub-variants XBB and XBB.1.5 as it was against earlier sub-variants. Based on North Carolina vaccine registry data for those over age 12, the booster showed 58.7% effectiveness against hospitalization compared to 25% for the original monovalent vaccine, as well as 61.8% effectiveness against infection versus 24.9% for the earlier vaccine.

But this research shows effectiveness only “for at least the first three months after vaccination,” as does most other Covid vaccine research. I’ve had two bivalent boosters, the last one five months ago, and am having trouble finding out whether and how to get what would be my sixth Covid vaccine. With new information about how vaccination might boost brain health, I’m ready for my next shot.

—Mary Carpenter regularly reports on need-to-know topics in health and medicine.