Herpes zoster as a vaccine-preventable risk factor increases the risk of dementia: A nested case-control study in Chinese population

Herpes zoster, a vaccine-preventable disease caused by the reactivation of varicella-zoster virus, has been linked to an increased risk of dementia in high-income countries. However, evidence from populations with low vaccination coverage remains limited. To address this gap, we conducted a nested case-control study using electronic health records from Yichang, China. A total of 51,843 incident dementia patients aged 50 y and older were matched with 338,877 controls by sex, age, and visit date. A documented clinical history of herpes zoster was significantly associated with an elevated risk of all-cause dementia (adjusted odds ratio [aOR] = 1.48; 95% confidence interval [CI]: 1.41-1.56), with the highest risk observed among individuals with herpes zoster involving the central nervous system (aOR = 1.59, 95%CI: 1.46-1.73). Among the dementia cases with prior HZ diagnosis, both Alzheimer's disease (aOR = 1.44, 95%CI: 1.14-1.79) and vascular dementia (aOR = 1.82, 95%CI: 1.49-2.21) showed increased risks following herpes zoster infection, with vascular dementia demonstrating a stronger association and more rapid progression (median time from first herpes zoster diagnosis to dementia onset: 1.5 y versus 2.2 y for Alzheimer's disease). The findings, derived from a population with minimal herpes zoster vaccination coverage, identify herpes zoster as a potentially modifiable risk factor for dementia. These also underscore the potential dual public health benefit of herpes zoster vaccination in preventing both acute infection and long-term cognitive decline.