Researchers look more deeply into the possible role of herpes zoster in dementia

Could shingles increase patients’ risk for dementia? And if an association is established, could shingles vaccination protect against it? Or is it “healthy vaccinee bias” at play? What about the potential for adult vaccines against other infections? Researchers wants answers to these questions, according to a recent article in the Journal of American Medicine (JAMA).According to the Public Health Agency of Canada, nearly one in three Canadians develops herpes zoster in their lifetime. There are an estimated 130,000 new cases of shingles in Canada each year, 17,000 of which lead to of post-herpetic neuralgia and 20 of which lead to death via complications. As explained in the JAMA article, infections in general are emerging as a risk factor for dementia, noting that before penicillin, syphilis infection was a main cause of dementia. The article also stated that the idea of infection, especially shingles, being the cause of dementia has gained in attention in part because long-standing wisdom around the etiology of Alzheimer’s is losing ground. The hypothesis that a major cause of Alzheimer’s is the accumulation of amyloid-B protein in the brain has not been borne out by recent studies.Mixed resultsThe article spoke to experts who pointed out that research studies on the relationship between infections, vaccines and dementia risk have been observational, with mixed results—some finding no association and others suggesting infections increase dementia risk and that vaccines lower it.Observational studies on vaccines are challenging due to potential bias: People who choose to get vaccinated are often healthier than those who don't, making it hard to account for factors like smoking, alcohol use or weight, all of which are linked to dementia risk. This “healthy vaccinee bias” is difficult to eliminate in such studies.However, a study published in Nature Medicine in July (and reported on in the Medical Post) was unique in that it got around usual healthy vaccinee bias because there was a rapid switch from the old Zostavax (zoster vaccine live) vaccine to the new Shingrix (recombinant zoster) vaccine in the U.S. Using health records, the researchers compared nearly 104,000 each of those who had received the old and new vaccines.The study showed that, compared to those who received the older vaccine, the recombinant shingles vaccine was linked to a significantly lower risk of dementia within six years after vaccination. Specifically, it extended diagnosis-free time by 17%, equivalent to 164 additional days without a dementia diagnosis. “It might well be that the vaccine is delaying dementia rather than preventing it altogether,” said lead author Dr. Maxime Taquet, a psychiatrist at the University of Oxford.Pneumococcal vaccinesSome research suggests compromised immunity rather than a specific pathogen may be what is playing a role in Alzheimer's disease. Svetlana Ukraintseva and colleagues from Duke University’s Social Science Research Institute researched this and published their results in a June 2024 article in Experimental Gerontology.The authors found that shingles, pneumonia and fungal infections diagnosed between ages 65 and 75 were associated with a 16% to 42% higher risk of Alzheimer’s disease later in life. In contrast, the shingles and pneumococcal vaccines given at the same ages were associated with a 15%-to-21% lower risk. Vaccines may rejuvenate the aging immune system, the authors noted, though live and non-live vaccines could have different effects. And while infections may increase dementia risk, they could also enhance the immune system’s ability to fight cancer. “Trade-offs are everywhere,” Ukraintseva wrote.Another study showed that vaccination against herpes zoster, pneumococcus and tetanus/diphtheria reduced Alzheimer’s risk by about 3% after eight years. Infections may contribute to brain inflammation and neurodegeneration, noted author Dr. Paul Schulz, and vaccines might reduce this risk by preventing or lessening the severity of infections.With an aging population and dementia (and shingles) becoming more common with age, it’s an urgent area of study, noted the JAMA article.

Researchers look more deeply into the possible role of herpes zoster in dementia

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