Recombinant Zoster Vaccination May Reduce Dementia Risk in Older Adults

1. In this target trial emulation, receipt of the recombinant zoster vaccine (RZV) was associated with a reduced risk of dementia among older adults admitted to skilled nursing facilities.

2. The association was more pronounced among women and among individuals who had not previously received the live attenuated herpes zoster vaccine.

Evidence Rating Level: 2 (Good)

Study Rundown: Several studies have reported an association between herpes zoster (HZ) infection and an increased risk of dementia. Because the recombinant zoster vaccine (RZV) substantially reduces HZ incidence in older adults, there has been growing interest in whether vaccination may also lower dementia risk. Previous research demonstrated a reduced risk of dementia among recipients of the live attenuated HZ vaccine; however, this vaccine is no longer available in the United States. This study evaluated the association between RZV administration and dementia risk among nursing facility residents who were vaccinated either during admission or, if discharged, within 12 months of admission. Individuals who received RZV experienced a 24% lower relative risk of developing dementia compared with those who were not vaccinated. The protective association was more pronounced among women and among individuals who had not previously received the live HZ vaccine. Subgroup analyses restricted to participants without evidence of cognitive impairment at baseline yielded similar results, supporting the robustness of the findings. Sensitivity analyses using a broader definition of dementia, including any dementia-related diagnostic code or initiation of anti-dementia medication, also demonstrated a protective association, although the effect was attenuated when the outcome was limited to new anti-dementia medication use alone. Additionally, RZV recipients had a lower risk of death during follow-up. Despite these promising findings, a negative control analysis revealed an association between RZV receipt and increased wellness visits, suggesting the presence of residual confounding and limiting causal inference. Overall, the study provides evidence that RZV may reduce dementia risk in older adults, although pragmatic randomized controlled trials are needed to confirm this potential benefit.

Click to read this study in AIM

Relevant Reading: Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis

In-Depth [retrospective cohort study]: This target trial emulation evaluated the association between recombinant zoster vaccine (RZV) administration and dementia risk among older adults admitted to skilled nursing facilities for post-acute or long-term care in the United States. Data were obtained from a large nursing home electronic health record vendor and linked Medicare databases, providing information on demographics, clinical assessments, medications, vaccinations, and healthcare utilization. The study included new admissions between January 1, 2017, and December 31, 2022. Residents were excluded if they were younger than 66 years, lacked continuous Medicare coverage during the preceding year, had pre-existing dementia, were receiving hospice care, had recent herpes zoster infection, had previously received RZV, or had died before the index date. The primary outcome was incident dementia, defined using validated combinations of dementia-related diagnostic codes and anti-dementia medication use. A total of 509,926 residents from 5,550 skilled nursing facilities were included (mean age 79.3 years; 63.6% women). After 12 months of follow-up, 8,843 individuals received at least one RZV dose, of whom 69% completed the two-dose series. Most vaccinations (87%) occurred after discharge from the facility. Compared with unvaccinated participants, vaccinated individuals were slightly younger, had fewer comorbidities, and were more likely to have previously received the live attenuated zoster vaccine. Over four years, the unadjusted cumulative incidence of dementia was 18.3% among vaccinated participants and 24.8% among unvaccinated participants. After adjustment using inverse probability weighting, RZV administration within 12 months of admission was associated with a 24% relative reduction in dementia risk (relative risk, [RR] 0.76; 95% confidence interval [CI], 0.69-0.84). The association was stronger in women and in those without prior receipt of the live zoster vaccine. Similar findings were observed among participants without baseline cognitive impairment and across multiple sensitivity analyses. RZV was also associated with lower mortality (RR 0.76; 95% CI 0.75-0.76). Although negative control analyses suggested some residual confounding, the association remained attenuated but significant after calibration. Overall, these findings suggest that RZV may be associated with a reduced risk of dementia among older adults admitted to nursing facilities.

Image: PD

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