A recent large analysis of more than 400 000 American adults suggested that two AS01-adjuvanted vaccines for different pathogens – the respiratory syncytial virus (RSV) vaccine (Arexvy) and the recombinant shingles vaccine (Shingrix) – were tied directly to a lower dementia risk, reports Medpage Today.
Compared with the flu vaccine, the AS01-adjuvanted RSV vaccine was associated with a 29% increase in time without a dementia diagnosis, with a restricted mean time lost [RMTL] ratio of 0.71 (95% CI 0.61-0.83) over 18 months, reported Paul Harrison, BMBCh, DM, of the University of Oxford in England, and colleagues.
For the AS01-adjuvanted shingles vaccine, the RMTL ratio was 0.82 (95% CI 0.74-0.91). Among people who received both AS01 vaccines, the RMTL ratio was 0.63 (95% CI 0.55-0.72).
Both the RSV vaccine and the recombinant shingles vaccine contain an AS01 adjuvant to stimulate the immune system; the flu vaccine does not.
“No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk,” Harrison and co-authors wrote in npj Vaccines.
Previous work by Harrison and colleagues showed the recombinant shingles vaccine was tied to a lower risk of dementia over six years than the live shingles vaccine (Zostavax).
“We wanted to investigate why Shingrix appears more effective than Zostavax in reducing the incidence of dementia. One possibility is that Shingrix contains the AS01 adjuvant, whereas Zostavax does not,” Harrison told MedPage Today.
"We therefore looked at the risk of dementia after the Arexvy RSV vaccine, which contains the same adjuvant, and found it had the same effect on dementia risk as Shingrix,” he said. “While this finding does not prove that the adjuvant is important, it supports the possibility.”
Several studies have shown an association between shingles vaccination and a reduced rate of dementia, noted immunologist Andrew Pollard, MBBS, PhD, of the University of Oxford, who wasn’t involved with the research.
“However, this latest study shows that another vaccine, against the completely unrelated respiratory virus, RSV, is also associated with a reduced rate of dementia. The authors argue this is because of a non-specific effect of these vaccines on the immune system which generates an environment in our bodies that is somehow protective against dementia, though further studies are needed to confirm this,” Pollard wrote on the UK Science Media Centre website.
“Such a mechanism could account for the effects driven by both shingles and RSV vaccines,” he added. “The various studies of the impact of vaccination on dementia are all observational studies, which could have a risk of bias, as it can be challenging to adequately control for differences between those who seek vaccination and those who don’t, but the consistent finding across multiple studies makes the observation more convincing.”
Harrison and colleagues evaluated electronic health record (EHR) data for older US adults in the TriNetX network, including 35 938 people who received the AS01 RSV vaccine only, 103 798 people who received the AS01 shingles vaccine only, and 78 658 who received both.
These were matched with an equal number of people who received the flu vaccine and neither the shingles nor RSV vaccine. Cohorts were matched for 66 covariates, including socio-demographic factors, comorbidities, history of herpes infection, and history of influenza vaccination.
The index date was on or after 1 May 2023, the date the FDA approved the AS01 RSV vaccine. People diagnosed with dementia, Alzheimer’s, Parkinson’s, or other neurodegenerative diseases before the index date or three months after were excluded from the analysis.
The EHR code used to identify the RSV vaccine covered both the AS01-adjuvanted RSV vaccine and a recombinant RSV vaccine that did not contain AS01 (Abrysvo). People identified as having the recombinant RSV vaccine were excluded from the study. Not all records specified an RSV vaccine brand: the researchers estimated that 76% of the cohort had the AS01-adjuvanted shot.
The study was subject to the limitations of EHR data, including no validation of diagnoses and sparse data about socio-economic and lifestyle factors, Harrison and co-authors acknowledged. Unmeasured confounders may have influenced results.
Being diagnosis-free does not mean being disease-free because there can be diagnostic delays, the researchers pointed out.
“However, if diagnostic delays are similar between cohorts, then differences in disease-free time will follow differences in diagnosis-free time,” they noted.
Study details
Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections
Maxime Taquet, John Todd & Paul Harrison.
Published in NPJ Vaccine on 25 June 2025
Abstract
AS01-adjuvanted shingles (herpes zoster) vaccination is associated with a lower risk of dementia, but the underlying mechanisms are unclear. In propensity-score matched cohort studies with 436,788 individuals, both the AS01-adjuvanted shingles and respiratory syncytial virus (RSV) vaccines, individually or combined, were associated with reduced 18-month risk of dementia. No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk.
Medpage Today article – RSV Vaccine Tied to Lower Dementia Risk (Open access)
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