There is growing interest in the possibility that Alzheimer's disease is triggered by infection because the Alzheimer's disease brain signature protein, β-amyloid peptide, has antimicrobial activity and therefore β-amyloid peptide could be a consequence rather than a cause of Alzheimer's disease. Several observational cohort and case-control studies have shown reduced rates of dementia after certain types of vaccines. Twenty years ago, Verreault and his colleagues reported that vaccine exposure (diphtheria / tetanus, polio, influenza) was associated with a 25-60% reduction in the subsequent development of Alzheimer's disease.
Klinger and colleagues have demonstrated a significantly reduced risk of developing Alzheimer's disease in patients with bladder cancer exposed to repeated intravesical applications of the Bacillus Calmette-Guérin vaccine, particularly in the 75+ year-old population.
Scherrer and his colleagues showed a significantly reduced rate of dementia in people vaccinated against tetanus, diphtheria and pertussis and shingles compared to those unvaccinated.
Liu and his colleagues found a reduced rate of dementia in patients with chronic kidney disease vaccinated with the influenza vaccine.
Population-wide observational cohort studies indicate a moderate association between a diagnosis of human herpes virus infection and incident dementia, and some studies indicate a potential mediating role of antiherpetic drugs.
The varicella-zoster virus (called VZV, for varicella-zoster virus) is a herpesvirus, also called HHV-3 (human herpesvirus 3), which causes chickenpox or shingles.
Human herpes viruses, also known as varicella-zoster virus, are usually contracted in early childhood when they cause chickenpox, but the virus persists throughout life and may recur in older people as shingles, and has also been associated with postherpetic neuralgia, encephalitis and / or meningitis, and respiratory disease.
To reduce the effects of the re-emergence of human herpes viruses in the elderly, national vaccination strategies have been implemented in the UK and elsewhere.
In Wales, a national shingles vaccination has been carried out since 2013, with the aim of vaccinating people aged 70 years, and a catch-up vaccination at 79 years for unvaccinated people at 70 years.
Until 2018, the only shingles vaccine available in Wales was a live attenuated vaccine against the human herpes virus (Zostavax). Since June 2018, a small proportion of the Welsh population has received the recombinant shingles vaccine (Shingrix).
In this new pre-print publication, Christian Schnier, Janet Janbek, Richard Lathe and Jürgen Haas analyzed the association of shingles vaccination with incident dementia in people vaccinated in Wales between 2013 and 2020 in an observational cohort study using national health data collected retrospectively. In addition, they analyzed whether this association was mediated by a reduction in diagnosed shingles and whether the association had a different degree in Alzheimer's disease and vascular dementia.
People exposed to the vaccine had a 39% reduced risk of being diagnosed with dementia after vaccination. This association is close to that published by Scherrer and colleagues who found a 43% reduction in dementia in people vaccinated against shingles.
The reduction in dementia in people exposed to the vaccine was slightly more pronounced for vascular dementia than for Alzheimer's disease. If true, their results suggest an association between shingles vaccination and cerebrovascular disease, rather than an association of vaccination with the pathological accumulation of toxic proteins in the brain such as the beta-amyloid peptide and the protein tau.
However, their results should be interpreted with caution because the total duration of follow-up of those vaccinated and subsequently diagnosed with herpes zoster was low, resulting in wide confidence intervals in the estimate. People exposed to the shingles vaccine had a lower risk of death from all causes except cancer, this finding could indicate a nonspecific effect of the shingles vaccination.
One potential interpretation of their results, therefore, is that the live attenuated varicella-zoster vaccine acts as an adjuvant that plays a role in immune responses against viruses.
This interpretation is supported by: (i) documented cross-immune protection when infection with one pathogen can alleviate disease caused by a second unrelated pathogen, (ii) the fact that an immune adjuvant (alum) has been reported to delay the development of Alzheimer's disease, (iii) the fact that a potent adjuvant vaccine (Bacillus Calmette-Guérin) reduces the rates of Alzheimer's disease in patients with bladder cancer.
These theories of the negative association between varicella zoster virus vaccination and dementia, however, should be considered, alongside other potential theories. Indeed, their results could come from a selection bias. Indeed, non-specific effects of the vaccine, such as lower mortality, have already been described in observational cohort studies of vaccine efficacy by Simonsen and colleagues, who attributed the association to selection bias for fragility .
To control for the selection bias of frailty, scientists at the Universities of Edinburgh and Copenhagen adjusted frailty between 65 and 70 years of age, retirement home residency, and the multiple illnesses that make up the Charlson Co-morbidity Index.
The authors cannot exclude with certainty that unvaccinated people may have a lower healthy life expectancy. This observation would be supported by the results of vaccine efficacy studies for Zostavax, which showed no significant difference in mortality between people exposed to the vaccine and those exposed to a placebo.
In addition, although their study population was large and representative of the Welsh population, the average follow-up period was rather short, as the introduction of the vaccine into a national campaign was made in 2013, which gave maximum follow-up time. about 6 years old (up to the age of 76).