Vaccination for the herpes zoster virus that causes shingles is generally done after age 50. Evidence from widely used vaccines suggests that many forms of vaccination produce long-term trained immunity effects, which include increased resistance to unrelated pathogens, and a reduction in innate immune system inflammatory signaling in older individuals. Insofar as vaccination is connected with reduced incidence of an inflammatory disease, this may well be the important mechanism. Equally, in the case of Alzheimer's disease, some evidence suggests that persistent viral infection may be an important contributing factor in the onset and progression of this condition for other reasons. None of this is completely cut and dried - there are contradictory findings and clinical trial outcomes. But on balance, the evidence leans towards a protective effect of vaccination.
Clinical and subclinical reactivations of the neurotropic herpesvirus (the varicella zoster virus) that causes chickenpox and shingles may constitute a chronic immune stressor that drives inflammatory pathways in both the peripheral and central nervous system, interfering with neuroimmune homeostasis in older age. The varicella zoster virus has also recently been linked to amyloid deposition and aggregation of tau proteins, as well as cerebrovascular disease that resembles the patterns commonly seen in Alzheimer's disease. Reducing clinical and subclinical reactivations of the virus through herpes zoster (HZ) vaccination might thus have a beneficial impact on the development or progression of dementia, as well as neuroimmune health and cognitive reserve in older age more broadly.
Moreover, it is possible that HZ vaccination, and potentially vaccinations in older age more generally, act on the dementia disease process through a pathogen-independent immune mechanism. Such an effect might counteract immunosenescence and would add to the growing body of evidence suggesting that vaccines frequently have broader health benefits beyond their intended target.
Using natural experiments, we have previously reported that live-attenuated HZ vaccination appears to have prevented or delayed dementia diagnoses in both Wales and Australia. Here, we find that HZ vaccination also reduces mild cognitive impairment diagnoses and, among patients living with dementia, deaths due to dementia. Exploratory analyses suggest that the effects are not driven by a specific dementia type. Our approach takes advantage of the fact that individuals who had their eightieth birthday just after the start date of the HZ vaccination program in Wales were eligible for the vaccine for 1 year, whereas those who had their eightieth birthday just before were ineligible and remained ineligible for life. The key strength of our natural experiments is that these comparison groups should be similar in all characteristics except for a minute difference in age. Our findings suggest that live-attenuated HZ vaccination prevents or delays mild cognitive impairment and dementia and slows the disease course among those already living with dementia.
Link: https://doi.org/10.1016/j.cell.2025.11.007
View the full article at FightAging
