Dr. Margarita Fedorova discusses whether a vaccine ingredient is quietly protecting the brain. Show citation: Taquet M, Todd JA, Harrison PJ. Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections. NPJ Vaccines. 2025;10(1):130. Published 2025 Jun 25. doi:10.1038/s41541-025-01172-3 Show transcript: Dr. Margarita Fedorova: Welcome to Neurology Minute. My name is Margarita Fedorova, and I'm a neurology resident at the Cleveland Clinic. Today we're exploring a study that raises a compelling question. Could a vaccine ingredient be quietly protecting the brain? A recent study by Taquet et al., published in npj Vaccines in 2025, investigated whether vaccination with an AS01-adjuvanted vaccine is associated with a lower risk of dementia. You might know it as the immune-boosting ingredient in Shingrix, the shingles vaccine, and Arexvy, the new RSV vaccine. We already know from prior work that the Shingrix vaccine was associated with a reduced risk of dementia, but the question this paper asks is why. Is it because preventing shingles itself protects the brain, or is there something specific about the adjuvant that's doing the work? To answer this, the researchers used a large US electronic health record database comparing over 35,000 people who received the AS01-adjuvanted RSV vaccine, over 100,000 who received the AS01-adjuvanted shingles vaccine and over 78,000 who received both. Each matched against individuals who got the seasonal flu vaccine instead. The findings were interesting. People who received the RSV vaccine had a 29% lower risk of new dementia diagnosis over the following 18 months. Those who received the shingles vaccine had an 18% increase in time without dementia, and those who received both had a 37% increase in dementia-free time. Here's a key insight. Both vaccines target completely different viruses, but both contain the same adjuvant. The fact that a similar protective signal was seen with both suggests the benefit may not be about which virus is prevented, and it may be about the AS01 itself. Why might an adjuvant protect the brain? AS01 contains two active components, monophosphoryl lipid A, known as MPL, and QS21. Together they activate macrophages and dendritic cells, triggering cascade that includes a production of interferon gamma. In animal models, stimulation of a receptor called toll-like receptor 4, which MPL activates, has been shown to reduce Alzheimer's-like pathology. The authors also point out that the protective effect appears within just a few months of vaccination, which is hard to explain purely by prevented infections and may point instead to a direct immunological mechanism. Very important caveat. This is an observational study, not a randomized trial, so we can't prove causation. There was also uncertainty about which brand of RSV vaccines some patients received, which could affect the strength of the AS01-specific conclusion. And with all of the dementia studies, it's unclear whether the vaccines prevent dementia or delay its onset. Though even a delay would be clinically meaningful given how few tools we have. What does this mean for clinical practice? For now, it doesn't change your vaccination recommendations. Both Shingrix and Arexvy already indicated in appropriate patients for the primary purposes, but it adds an intriguing possible benefit when counseling patients who ask about vaccines. And it opens the door to a genuinely exciting question. If AS01 has neuroprotective properties, could it be studied in a therapeutic target in its own right? That's the Neurology Minute for today. Keep exploring and we'll see you next time. If you want to read more, please find the paper by Maxime Taquet, et al., titled Lower Risk of Dementia with AS01-Adjuvanted Vaccination Against Shingles and Respiratory Syncytial Virus Infections, published in npj Vaccines in June 2025.

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