Abstract
BACKGROUND: Herpes zoster (HZ) infection increases dementia risk, but it is not known if herpes zoster vaccination is associated with lower risk for dementia. We determined if HZ vaccination, compared to no HZ vaccination, is associated with lower risk for incident dementia. METHODS AND FINDINGS: Data was obtained from Veterans Health Affairs (VHA) medical records (10/1/2008-9/30/2019) with replication in MarketScan® commercial and Medicare claims (1/1/2009-12/31/2018). Eligible patients were ≥65 years of age and free of dementia for two years prior to baseline (VHA n = 136,016; MarketScan n = 172,790). Two index periods (either start of 2011 or 2012) were defined, where patients either had or did not have a HZ vaccination. Confounding was controlled with propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between HZ vaccination and incident dementia in all patients and in age (65-69, 70-74, ≥75) and race (White, Black, Other) sub-groups. Sensitivity analysis measured the association between HZ vaccination and incident Alzheimer's dementia (AD). HZ vaccination at index versus no HZ vaccination throughout follow-up. VHA patients mean age was 75.7 (SD±7.4) years, 4.0% were female, 91.2% white and 20.2% had HZ vaccination. MarketScan patients mean age was 69.9 (SD±5.7) years, 65.0% were female and 14.2% had HZ vaccination. In both cohorts, HZ vaccination compared with no vaccination, was significantly associated with lower dementia risk (VHA HR = 0.69; 95%CI: 0.67-0.72; MarketScan HR = 0.65; 95%CI:0.57-0.74). HZ vaccination was not related to dementia risk in MarketScan patients aged 65-69 years. No difference in HZ vaccination to dementia effects were found by race. HZ vaccination was associated with lower risk for AD. CONCLUSIONS: HZ vaccination is associated with reduced risk of dementia. Vaccination may provide nonspecific neuroprotection by training the immune system to limit damaging inflammation, or specific neuroprotection that prevents viral cytopathic effects.