Eyting M, Xie M, Michalik F, Heß S, Chung S, Geldsetzer P.
A natural experiment on the effect of herpes zoster vaccination on dementia.
Nature. 2025 Apr 2; Epub 2025 Apr 2
PubMed.
A recent report on the protective effects of vaccines regarding dementias is admirable and encouraging. However, I'd like to offer a wider perspective.
The first report that vaccines might retard dementia was published 23 years ago by researchers in Canada (Verreault et al., 2001), followed by more than 20 reports confirming the protective effect (Greenblatt and Lathe, 2024). Because not all these studies are cited by Eyting et al., we summarize the overall position.
First, all vaccines tested show some protective effect, irrespective of which specific microbial agent they target. These include diphtheria, hepatitis, herpes zoster, influenza, pneumococcus, tuberculosis (BCG), and typhoid. Second, an adjuvant-only vaccine preparation also displayed benefits. Third, the protection was dose-dependent—more vaccine, more protection. In a different study, of more than 700 routinely prescribed medications, only four had protective effects, and all were vaccines (Wilkinson et al., 2022). Overall, despite large variations between different studies, vaccine administration may reduce subsequent overall dementia incidence by up to 50 percent.
These findings are inconsistent with agent-specific protection. Diverse microbes are being found in Alzheimer's disease brain, ranging from bacteria to fungi to viruses, all of which could potentially cause neuronal dysfunction. Instead, the vaccine studies point directly to nonspecific immune boosting—the concept of immunopotentiation or "trained immunity," as elegantly put forward by Mihai Netea, Peter Aaby, and others—that specific microbial agents, and/or the molecules they release, provoke beneficial changes in the immune system that can last for months to years or more (Netea et al., 2020; Aaby et al., 2023).
There is broadening evidence that the development of dementing illnesses may be linked to diverse infections that can each precipitate neuronal dysfunction. In this wider context, the nonspecific effects of vaccines—and their associated adjuvants—that can spur the immune system warrant greater attention as a cost-effective public health measure.
Written with Charles Greenblatt.
References:
Aaby P, Netea MG, Benn CS.
Beneficial non-specific effects of live vaccines against COVID-19 and other unrelated infections.
Lancet Infect Dis. 2023 Jan;23(1):e34-e42. Epub 2022 Aug 26
PubMed.
Xie M, Eyting M, Bommer C, Ahmed H, Geldsetzer P.
The effect of herpes zoster vaccination at different stages of the disease course of dementia: Two quasi-randomized studies.
medRxiv. 2024 Aug 23;
PubMed.
Greenblatt CL, Lathe R.
Vaccines and Dementia: Part II. Efficacy of BCG and Other Vaccines Against Dementia.
J Alzheimers Dis. 2024;98(2):361-372.
PubMed.
Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LA, van der Meer JW, Mhlanga MM, Mulder WJ, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E.
Defining trained immunity and its role in health and disease.
Nat Rev Immunol. 2020 Jun;20(6):375-388. Epub 2020 Mar 4
PubMed.
Verreault R, Laurin D, Lindsay J, De Serres G.
Past exposure to vaccines and subsequent risk of Alzheimer's disease.
CMAJ. 2001 Nov 27;165(11):1495-8.
PubMed.
Wilkinson T, Schnier C, Bush K, Rannikmäe K, Lyons RA, McTaggart S, Bennie M, Sudlow CL.
Drug prescriptions and dementia incidence: a medication-wide association study of 17000 dementia cases among half a million participants.
J Epidemiol Community Health. 2022 Mar;76(3):223-229. Epub 2021 Oct 27
PubMed.
Comments
University of Edinburgh
A recent report on the protective effects of vaccines regarding dementias is admirable and encouraging. However, I'd like to offer a wider perspective.
The first report that vaccines might retard dementia was published 23 years ago by researchers in Canada (Verreault et al., 2001), followed by more than 20 reports confirming the protective effect (Greenblatt and Lathe, 2024). Because not all these studies are cited by Eyting et al., we summarize the overall position.
First, all vaccines tested show some protective effect, irrespective of which specific microbial agent they target. These include diphtheria, hepatitis, herpes zoster, influenza, pneumococcus, tuberculosis (BCG), and typhoid. Second, an adjuvant-only vaccine preparation also displayed benefits. Third, the protection was dose-dependent—more vaccine, more protection. In a different study, of more than 700 routinely prescribed medications, only four had protective effects, and all were vaccines (Wilkinson et al., 2022). Overall, despite large variations between different studies, vaccine administration may reduce subsequent overall dementia incidence by up to 50 percent.
These findings are inconsistent with agent-specific protection. Diverse microbes are being found in Alzheimer's disease brain, ranging from bacteria to fungi to viruses, all of which could potentially cause neuronal dysfunction. Instead, the vaccine studies point directly to nonspecific immune boosting—the concept of immunopotentiation or "trained immunity," as elegantly put forward by Mihai Netea, Peter Aaby, and others—that specific microbial agents, and/or the molecules they release, provoke beneficial changes in the immune system that can last for months to years or more (Netea et al., 2020; Aaby et al., 2023).
There is broadening evidence that the development of dementing illnesses may be linked to diverse infections that can each precipitate neuronal dysfunction. In this wider context, the nonspecific effects of vaccines—and their associated adjuvants—that can spur the immune system warrant greater attention as a cost-effective public health measure.
Written with Charles Greenblatt.
References:
Aaby P, Netea MG, Benn CS. Beneficial non-specific effects of live vaccines against COVID-19 and other unrelated infections. Lancet Infect Dis. 2023 Jan;23(1):e34-e42. Epub 2022 Aug 26 PubMed.
Xie M, Eyting M, Bommer C, Ahmed H, Geldsetzer P. The effect of herpes zoster vaccination at different stages of the disease course of dementia: Two quasi-randomized studies. medRxiv. 2024 Aug 23; PubMed.
Greenblatt CL, Lathe R. Vaccines and Dementia: Part II. Efficacy of BCG and Other Vaccines Against Dementia. J Alzheimers Dis. 2024;98(2):361-372. PubMed.
Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LA, van der Meer JW, Mhlanga MM, Mulder WJ, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Jun;20(6):375-388. Epub 2020 Mar 4 PubMed.
Verreault R, Laurin D, Lindsay J, De Serres G. Past exposure to vaccines and subsequent risk of Alzheimer's disease. CMAJ. 2001 Nov 27;165(11):1495-8. PubMed.
Wilkinson T, Schnier C, Bush K, Rannikmäe K, Lyons RA, McTaggart S, Bennie M, Sudlow CL. Drug prescriptions and dementia incidence: a medication-wide association study of 17000 dementia cases among half a million participants. J Epidemiol Community Health. 2022 Mar;76(3):223-229. Epub 2021 Oct 27 PubMed.
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