Abstract
BACKGROUND: Herpes zoster is a potential risk factor for dementia. The effectiveness of the recombinant zoster vaccine for preventing dementia is uncertain. METHODS: This retrospective cohort study used de-identified claims data from the Optum Labs Data Warehouse database from January 1, 2017, to December 31, 2022, to determine whether the recombinant zoster vaccine is associated with a reduced risk of dementia. Immunocompetent patients with ≥365 days of continuous enrollment were included, with the risk period starting upon age-eligibility for the recombinant zoster vaccination. Cox regression adjusted for time-fixed and time-updated measures every six months was implemented to estimate hazard ratios for dementia. Herpes zoster diagnosis and antiviral therapy were also assessed. RESULTS: There were 4,502,678 individuals (median [IQR] age, 62 [54-71] years; 51 % female) included in this study: 206,297 (4.6 %) were partially vaccinated, and 460,413 (10.2 %) were fully vaccinated. The incidence rate of dementia was 99.1 cases per 10,000 person-years in the fully vaccinated group, 108.2 cases per 10,000 person-years in the partially vaccinated group, and 135.0 cases per 10,000 person-years in the unvaccinated group. After adjustment, vaccination was significantly associated with a decreased risk of dementia for two doses (hazard ratio (HR): 0.68; 95 % CI: 0.67-0.70; P < .001) and for one dose (HR 0.89; 95 % CI: 0.87-0.92; P < .001). Having a herpes zoster diagnosis before the first vaccination dose was associated with an increased hazard of dementia (HR 1.47; 95 % CI: 1.42-1.52; P < .001) compared to those with no diagnosis. Antivirals used to treat zoster infection were protective against dementia (HR 0.42; 95 % CI: 0.40-0.44; P < .001). CONCLUSIONS: These findings suggest that the recombinant zoster vaccine is associated with a decreased risk of dementia and highlight an additional benefit of vaccination beyond preventing herpes zoster.