Varicela Zoster Vaccine is associated to reduction of Vascular Dementia

In a study recently published (Apr - 2022) in Alzheimer's Dement (NY) Reduced dementia incidence after varicella zoster vaccination in Wales 2013-2020 - PubMed (nih.gov), a population of 156,000 took the Varicella Zoster vaccine and was followed up from 2013 to 2020 in Wales.

Research into the association of vaccination with dementia serves several purposes. Any association would highlight the contribution of the immune system and/or of pathogens to the disease progression to dementia and would allow a deeper understanding of the natural history of dementia. In addition, vaccination strategies could be developed to cost-effectively reduce the rate of dementia.

Chronic infection with human herpes viruses (HHVs) has recently been highlighted as a potential contributing factor to the development of dementia, especially Alzheimer′s Dementia (AD). Population-wide observational cohort studies indicate a moderate to non-existing positive association of a diagnosis of HHV infection with incident dementia, and some studies point to a potential mediating role of antiherpetic medication.

The objective of this observational cohort study using retrospectively, collected national health data was to analyze the association of shingles vaccination with incident dementia in Wales between 2013 and 2020. Furthermore, the investigators analyzed whether that association was mediated by a reduction of diagnosed shingles and whether the association was different for AD than for vascular dementia (VaD).

People exposed to the vaccine had a 39% reduced hazard of dementia diagnosis after vaccination. This association is similar to the study by Scherrer et al. Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination | The Journals of Gerontology: Series A | Oxford Academic (oup.com) who found a 43% reduction in dementia in those vaccinated against shingles. It compares favourably to the modifiable risk factors for dementia in later life summarized in Livngston et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission - PubMed (nih.gov)smoking (relative risk [RR]: 1.6), depression (RR: 1.9), social isolation (RR: 1.6), physical inactivity (RR: 1.4), diabetes (RR: 1.5), and air pollution (RR: 1.1).

The reduction in dementia in those exposed to the vaccine was slightly more pronounced for VaD than for AD. This is an interesting finding because, none of the vaccine studies have separately analyzed dementia subtypes. If true, these findings point toward an association between shingles vaccination and cerebrovascular pathologies rather than an association of vaccination with the pathological accumulation of toxic proteins in the brain such as amyloid beta (Aβ) peptide and tau. Indeed, in addition to cutaneous, ocular, pulmonary, hepatic, and renal lesions, VZV infection has been implicated in vascular pathology, most prominently in cerebral arteries. VZV vasculopathy can develop in the absence of any skin rash, pointing to dissociation between cutaneous lesions (required for shingles diagnosis) and cerebrovascular pathology.

This study shows a clear association between shingles vaccination and reduced dementia incidence, which is consistent with other observational cohort studies. As such, non-exposure to a vaccine, be it a shingles vaccine or Tdap, could potentially be used as an early warning sign of deteriorating health, and it would be interesting to analyze whether vaccine exposure could be used in predictive modeling. Although it cannot exclude a true effect, these results lead to suspect that the unexpected greater association with VaD than with AD, and the fact that other vaccines such as Tdap and BCG were also associated with reduced dementia in other studies, points more to a selection bias associated with vaccination than a genuine vaccine effect. . Secondary analysis of results from randomized controls trials into the efficacy of shingles vaccination might provide important insights.?