Alterations in varicella-zoster virus immunity around dementia diagnosis in older adults.

Dementia is a multifactorial clinical syndrome, for which neurotropic herpes viruses have been proposed as potential contributors to disease etiology. While varicella-zoster virus (VZV) vaccination has been associated with reduced dementia risk, little is known about how longitudinal VZV-specific antibody dynamics relate to dementia diagnosis. To investigate this, we analysed VZV-specific IgM and IgG levels in 2,867 samples from 1,612 older adults living in nursing homes. Capillary blood samples were collected at seven sampling periods between 2021 and 2024. Antibody levels were linked to national registry data. Linear mixed-effects models assessed (i) pre-diagnostic differences in antibody levels between individuals who subsequently developed dementia and those who did not, (ii) longitudinal trajectories relative to diagnosis, and (iii) within-individual changes among participants with samples before and after diagnosis. VZV-IgM levels were lower in participants who were later diagnosed with dementia (estimate -0.075 log10, p = 0.037), with VZV-IgG showing a similar trend. Longitudinal models demonstrated increasing VZV antibody levels in the years surrounding dementia diagnosis, with significant yearly increases in IgM (estimate 0.0069 log10, p = 0.008) and a trend for elevated IgG, whereas no corresponding temporal changes were observed for RSV antibodies. Within a subset of participants with samples on both sides of diagnosis (n = 23), VZV-IgM and VZV-IgG levels showed consistent within-individual increases, although statistical power was limited. These findings align with epidemiological evidence linking VZV vaccination to reduced dementia risk and provide new insight into immunological changes accompanying dementia progression. Further studies are warranted to clarify causal mechanisms and the role of antiviral or vaccination strategies in dementia prevention.