Shingles vax tied to reduced dementia risk

Immunization with the non-live recombinant zoster vaccine (RZV) or live-attenuated zoster vaccine (ZVL) is associated with reductions in the risk of dementia relative to the 23-valent pneumococcal polysaccharide vaccine (PPSV23), according to a large observational study in adults aged ≥50 years.

“What originally piqued our interest are a number of scientific studies that have been implicating the role of herpes zoster (HZ) vaccination on the potential risk of dementia,” said Patrick Schwab from GSK, Baar, Switzerland, during his presentation at AAIC 2024. “We thus conducted a retrospective matched-cohort study to estimate the effect of HZ vaccination on all-cause dementia.”

Schwab and his team utilized the US Optum de-identified Electronic Health Record dataset, which covers 100+ million unique lives and 7,000+ hospitals and clinics. Data were collected over an average of around 7 years of follow-up. Cohorts were grouped by vaccine exposure (RZV, ZVL, and/or PPSV23). PPSV23 was chosen as an elective control although it does not target HZ.

Three matched cohorts were formed: RZV vs PPSV23 (n=168,667), ZVL vs PPSV23 (n=382,038), and RZV vs ZVL (n=45,851). To analyse the data, the team applied cutting-edge artificial intelligence and machine learning methodology to try to approximate a randomized clinical trial setting as closely as possible using covariate adjustments. This was also done to address a number of gaps such as the potential for confounding and the risk of selection bias.

Compared with PPSV23, both RZV and ZVL were associated with a reduction in the risk of dementia, but the effect was greater with the former (relative risk [RR], 0.76, 95 percent confidence interval [CI], 0.69–0.84; p<0.0001) than with the latter (RR, 0.86, 95 percent CI, 0.86–0.90; p<0.0001) at 3 years.

Although the effect appeared to have waned at 5 years, the reductions in the risk of dementia remained significant for both RZV (RR, 0.80, 95 percent CI, 0.71–0.90; p<0.0005) and ZVL (RR, 0.92, 95 percent CI, 0.89–0.95; p<0.0001) as opposed to PPSV23.

When comparing the two HZ vaccines, RZV outdid ZVL in reducing the risk of dementia at both 3 years (RR, 0.73, 95 percent CI, 0.60–0.89; p<0.005) and 5 years (RR, 0.77, 95 percent CI, 0.64–0.92; p<0.005).

There are no clear mechanisms that could explain for the protective effect of shingles vaccines against dementia. It could, however, be attributed to the vaccines’ protection against HZ, as the disease itself apparently increases the likelihood of developing dementia. [Neuron 2023;111:1086-1093; J Alzheimers Dis 2022;88:1189-1200]

The immunostimulants in the recombinant vaccine type may also factor in and may explain for its greater protective effect as opposed to the live-attenuated version of the vaccine. [Curr Opin Immunol 2019;59:42-48]

Schwab called for further investigations to establish a concrete causal relationship between HZ vaccination and reduced dementia risk. “These are quite exciting findings for their consistency, [but] the evidence warrants future follow-ups to better understand the association and the findings in totality.”

While extensive actions were taken to mitigate and quantify the risk of confounding, Schwab noted that unmeasured confounding cannot be fully ruled out given the retrospective nature of the study.

Compelling early results

“[Nonetheless, this] study adds to the growing body of evidence that suggests an association between shingles vaccination and reduced risk of dementia. These are compelling early results, which we are investigating further with additional retrospective and mechanistic studies to advance the field,” said GSK Chief Scientific Officer Tony Wood, in a separate report.

ZVL is no longer available for use in the US (as of November 2020). The US Centers for Disease Control and Prevention now recommends two doses of RZV for adults aged: 1) ≥50 years for the prevention of shingles and its associated complications; and 2) ≥19 years who are, or will be, immunosuppressed or immunodeficient. [https://www.cdc.gov/shingles/hcp/vaccine-considerations, accessed August 15, 2024]