Investigating the Neurological Impact of BCG and Influenza Vaccines on Dementia Risk

A tuberculosis vaccine rarely administered in the United States has reached the central nervous systems of older adults in a recent small-scale study, providing direct human evidence for a mechanism underlying a peculiar trend in dementia research.

Marc Weinberg of Massachusetts General Hospital and his colleagues conducted two related one-year, open-label trials involving 23 adults aged 55 and older, 11 of whom had biomarker evidence of Alzheimer’s-related pathology and 12 who did not. By utilizing lumbar punctures to sample cerebrospinal fluid, the researchers demonstrated that the Bacille Calmette-Guérin (BCG) vaccine reaches the brain and modifies immune activity there. The findings were published in July in Communications Medicine.

Weinberg clearly defined the boundaries of the study. What we didn’t do is prove that BCG prevents Alzheimer’s, he stated to CIDRAP News, emphasizing that the team also did not demonstrate that the vaccine treats the disease.

This distinction is crucial for the public. Three unrelated vaccines now exhibit a similar statistical association with reduced dementia rates, and the research has advanced a step closer to explaining the underlying “why” without bringing any closer to an official medical recommendation.

Spinal Fluid Evidence from 23 Older Adults

BCG prevents tuberculosis and is not routinely administered in the United States outside of specific uses, such as treating certain bladder cancers. Scientists at Mass General Brigham studying these off-label applications noticed that individuals receiving BCG appeared to develop Alzheimer’s and other dementias at lower rates.

The new research did not test whether this observation holds true. Instead, it examined a narrower, more mechanical question: whether the vaccine can reach the organ where the effect would theoretically occur.

Participants received two intradermal BCG doses a month apart, followed by blood and spinal fluid samples over the next year. The team discovered durable immune reprogramming in cerebrospinal fluid cells. Shifts in amyloid beta levels—lower in spinal fluid and higher in blood—appeared only in participants without Alzheimer’s-related changes at the outset, not in those who already had them.

With only twenty-three participants and an open-label design lacking a placebo group, the sample size is very small. What this establishes is biological plausibility, not clinical benefit.

Higher-Dose Flu Shots and a Sex Difference

Separate research from Paul Schulz and colleagues at UTHealth Houston has been building a parallel case around influenza vaccination for approximately seven years, following an unexpected signal flagged by a biomedical informatics team in their databases.

Their initial analysis, published in the Journal of Alzheimer’s Disease, compared adults aged 65 and older who received a flu vaccine with those who did not. Three years of vaccination was associated with roughly a 20 percent lower risk of Alzheimer’s, and six years with about a 40 percent lower risk, persisting for at least eight years.

The team then posed a more precise question. By comparing individuals who received a standard-dose flu vaccine with those who received a high-dose version, the healthy vaccinee problem is largely mitigated, as both groups are individuals who seek out vaccinations. In this comparison, published in Neurology and first-authored by Avram Samuel Bukhbinder, the high dose outperformed the standard dose by approximately 15 percent.

The researchers also reported that the apparent anti-dementia effect lasted roughly two years, far exceeding the four to six months of influenza protection, and that women appeared to benefit more from the high dose than men. Given that women develop Alzheimer’s about twice as often as men, this finding warrants further investigation.

Three Unrelated Vaccines, One Recurring Signal

Previous reporting highlighted a shingles vaccine study linking it to a lower dementia risk, which found a 24 percent lower relative risk across more than 500,000 older adults over four years. That work was led by Daniel Harris of the University of Delaware using nursing home records and Medicare claims, and was published in Annals of Internal Medicine. It was funded by GlaxoSmithKline, the manufacturer of the shingles vaccine, a disclosure readers should weigh alongside the finding.

What has changed since that report is the shape of the evidence rather than its strength. A shingles vaccine, an influenza vaccine, and a tuberculosis vaccine target completely different pathogens, yet all three now carry a similar association.

Researchers have offered mechanisms that differ by vaccine. For shingles, the varicella zoster virus resides in nerve tissue, can replicate in cerebral arteries, and raises stroke risk for up to a year after an episode; stroke is an established cause of vascular dementia. For influenza, the leading hypotheses involve the immune system either clearing amyloid plaque more efficiently or reacting to it less aggressively.

Glen Finney, who directs the Memory and Cognition Program at Geisinger Health, has framed the common thread as immune retraining and has raised the question of whether the effect belongs to vaccines broadly or to a specific subset. That remains unanswered.

Association Is Not Prevention

Every study described here is observational except the small BCG trials, and none demonstrates that a vaccine prevents dementia. Researchers involved in this work state that randomized trials comparing vaccines against placebo are the missing piece, as CIDRAP News reported.

Such trials would be slow and difficult. Because a person can receive a recombinant shingles vaccine from age 50 and cognitive changes may take many years to surface, follow-up would need to run for a long time, with all the attrition that implies.

The healthy vaccinee problem also persists. People who keep up with vaccines tend to be healthier, better connected to care, and more likely to have other protective habits, and statistical adjustment only goes so far. The high-dose versus standard-dose comparison addresses this more convincingly than most designs, but it does not eliminate it entirely.

For a household deciding on fall shots, the practical guidance remains unchanged. Influenza and shingles vaccination are recommended for older adults based on what those vaccines were designed to do: prevent serious infection, hospitalization, and death. BCG is not available for this purpose, and no one should seek it out based on a 23-person study.

A reasonable conversation with a clinician covers eligibility for the recombinant shingles vaccine, whether a high-dose or adjuvanted flu vaccine is appropriate at a given age, and what is covered under Medicare Part B or Part D. What is not reasonable is treating any of this as a dementia prevention plan, or delaying an appointment while waiting for trials that may take a decade to report.

Key Questions Answered

What is genuinely new here? A small trial demonstrated that the BCG tuberculosis vaccine reaches the human central nervous system and alters immune activity there, published in July. Separate flu vaccine research compared high-dose and standard-dose recipients.

Do vaccines prevent dementia? No study has shown that. The research describes statistical associations in observational data, and the researchers themselves say randomized trials are needed.

Should someone ask for a BCG vaccine? No. BCG is not used in the United States for this purpose, and the study involved 23 people and tested biology rather than benefit.

Why do three different vaccines show a similar pattern? The leading idea is that vaccination retrains the immune system in ways that may reduce brain inflammation, but the mechanism differs by vaccine, and none is confirmed.

Does this change flu or shingles vaccine advice? No. Both remain recommended for older adults based on infection prevention, which is a separate and far better established benefit.

What is the healthy vaccinee problem? People who get vaccinated tend to be healthier overall, which can make vaccines look more protective than they are. Comparing vaccine doses rather than vaccinated and unvaccinated groups reduces it.

Did women benefit more? In the high-dose flu comparison, researchers reported a larger apparent benefit in women. That finding comes from observational data and has not been confirmed in a trial.

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