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How the Shingles Vaccine Guards Against Dementia: New Clues
How do vaccines reduce dementia risk? A new study suggested that immune-boosting adjuvants contained in some vaccines may offer one explanation.
Adults who received the recombinant shingles vaccine Shingrix or the respiratory syncytial virus (RSV) vaccine Arexvy — both of which contain the AS01 adjuvant — had a lower risk for dementia in the 18 months after vaccination than peers who received the flu vaccine, which does not contain the AS01 adjuvant, investigators found.
'The findings are striking. We need studies to confirm whether the adjuvant present in some vaccines contributes to the reduced dementia risk and to understand how it does so,' senior author Paul Harrison, PhD, with the University of Oxford, Oxford, England, said in a statement.
The study was published online on June 25 in the journal npj Vaccines .
Vaccine or the Adjuvant?
For this study, investigators built on a prior analysis of the US patient database TriNetX that showed that adults who received the AS01 shingles vaccine had a lower risk for dementia than peers who received the older shingles vaccine (Zostavax), which does not contain the AS01 adjuvant.
To test the hypothesis that the AS01 adjuvant could be the key driver of the dementia-protective effect, researchers turned again to the TriNetX database and identified 103,798 people who received the AS01 shingles vaccine only, 35,938 who received the AS01 RSV vaccine only, and 78,658 who received both. These cohorts were propensity score matched to an equal number of people who received the flu vaccine and neither the shingles nor the RSV vaccine.
In the 18 months following vaccination, compared to those who received the flu vaccine, the risk for dementia diagnosis was 29% lower in those who received the AS01 RSV vaccine (restricted mean time lost [RMTL] ratio, 0.71) and 18% lower in those who received the AS01 shingles vaccine (RMTL, 0.82).
Individuals receiving both AS01 vaccines had a 37% reduced risk for dementia diagnosis (RMTL, 0.63).
These effects were consistent in men and women and were not explained by reductions in RSV or shingles infections alone. And no difference was observed between the two AS01 adjuvant vaccines, 'suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk,' the investigators said.
'Our data provide support for the hypothesis that, besides protection against their target infection, these vaccines could well protect against dementia via the action of the AS01 components through specific immunological pathways,' they wrote.
In particular, the AS01 adjuvant includes monophosphoryl lipid A (MPL), which activates immune cells, and QS-21, a plant-derived extract that amplifies the immune response.
Animal studies have shown that MPL can improve Alzheimer-related pathology, and other work suggests it triggers immune activity that might reduce the formation of amyloid plaques, a hallmark of Alzheimer's disease.
Caveats and Cautionary Notes
Several experts not involved in the study offered perspective on this research in a statement from the UK nonprofit Science Media Centre.
Julia Dudley, head of Research at Alzheimer's Research UK, said a strength of the study is that it adjusted for factors that could influence risk, such as underlying health conditions and some lifestyle and environmental factors.
'However, as the study is observational and examined past health data, the researchers cannot conclude how the Shingrix and Arexvy vaccines may protect against dementia. We also cannot rule out that the link between vaccine and dementia risk is due to other factors not captured in this study, such as social and lifestyle factors,' Dudley said.
A limitation of the study, highlighted by the authors, is that people could be living with dementia without having a formal diagnosis, 'which could skew the findings,' Dudley commented.
In addition, 'we do not know if the adjuvant is reducing the risk of dementia or delaying its onset. The follow-up period was only 18 months, so more research is needed to determine the potential long-term effects of the vaccines,' Dudley said.
Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, Milton Keynes, England, said the study is 'an interesting, worthwhile, and statistically competent piece of work, but a lot more research needs to be done to make good sense of its possible implications for healthcare.'
'Previous research has provided pretty convincing evidence that vaccination against shingles, in older people, can reduce dementia risk [but] exactly how AS01 might be involved in reducing dementia risk' is unclear, McConway said, and 'we're not yet anywhere near the stage of using the results of the new study to change clinical practice.'
Andrew Pollard, FMedSci, director of the Oxford Vaccine Group, University of Oxford, agreed.
'It is premature to be too certain about the mechanism by which vaccines might reduce dementia risk, but these observations provide further incentive for those eligible to turn up for their scheduled vaccination visits to prevent the unpleasant and potentially serious and life-threatening infections for which they were designed, but with the added possible benefit of a longer dementia-free lifespan. What's not to like?' Pollard commented.
