Association between recombinant herpes zoster vaccination and dementia risk in older adults newly admitted to post-acute and long-term care

Importance: Ecological and observational studies have shown a protective association between herpes zoster (HZ) vaccination and dementia risk, yet many had methodological limitations or examined the live HZ vaccine that is no longer available in the US. Improved access to linked electronic health records for patients receiving post-acute care and long-term care permit robust comparisons of dementia risk in adults eligible to receive the recombinant HZ vaccine. Objective: Emulate a randomized trial in observational data to estimate the association of the recombinant HZ vaccine (RZV) with incident dementia risk among older adults newly admitted for post-acute or long-term care in nursing homes (NHs). Design: Retrospective cohort study with target trial emulation and the clone censor approach. Setting: U.S. NHs that use PointClickCare as their electronic health record. Participants: Individuals who were admitted to a NH between 01/01/2017-12/31/2022; Medicare fee-for-service beneficiaries; did not have prevalent dementia; and eligible to receive RZV as of admission. Exposures: Receive one or more RZV doses within one year of admission vs. do not receive any RZV over four years of follow-up. Results: We identified 509,926 eligible NH residents (mean age 79 years; 36% men). Among those alive, uncensored, and without dementia at 12 months of follow-up, 8,843 received one or more doses of RZV. Receipt of RZV within one year of NH admission was associated with a 5.8% lower absolute risk (95%CI: -3.9% to -7.5%) of newly diagnosed dementia over four years (risk ratio [RR] = 0.76 [95%CI: 0.69-0.84]; cumulative incidence in 1+ RZV vs. no RZV: 18.8% vs. 24.6%). Associations were smaller in men (RR=0.82 [95%CI: 0.68-1.01]) and those with prior live HZ vaccination (RR=0.86 [95%CI: 0.65-1.09]). Bias analyses based on two negative control outcomes (NCOs) attenuated, but did not fully explain, the main effect of RZV on dementia risk (bias-adjusted RR = 0.82 [wellness visit NCO] and RR = 0.88 [hip fracture NCO]). Conclusions and Relevance: Administering RZV within 1 year of NH admission may reduce dementia risk. As RZV uptake was low overall, new NH residents would benefit from increased RZV vaccination uptake.