medwireNews: Giving the recombinant shingles vaccine to adults aged 65 years or older is associated with a significantly lower risk for dementia in the 6 years post-vaccination than the live alternative, which already offers some protection against the condition, shows a study published in Nature Medicine.
The study investigators report that individuals who received the recombinant vaccine were 17% less likely than those receiving the live vaccine to be diagnosed with dementia (a restricted mean time lost [RMTL] ratio of 0.83) in the 6 years following vaccination. This translated to an additional 164 days lived without a dementia diagnosis.
Maxime Taquet (University of Oxford, UK) and colleagues explain that they “leveraged a natural experiment opportunity in the United States,” as discontinuation of the live vaccine in October 2017 led to a rapid uptake of the recombinant vaccine enabling them to compare dementia incidence before and after the transition.
The investigators drew data from the electronic health records of more than 100 million patients from 62 healthcare organizations in the USA. They used propensity-score matching to compare 103,837 individuals (53.4% women), who received their first dose of shingles vaccine between November 2017 and October 2020 – 95% of whom received the recombinant vaccine – with the same number of individuals receiving their first dose between October 2014 and September 2017, 98% of whom received the live vaccine.
The cohorts were matched for 60 covariates, including sociodemographic factors (such as age, sex, ethnicity, race, and marital status), comorbidities, and history of herpes infection, as well as history of influenza vaccination. Individuals with a diagnosis of dementia, including vascular dementia, Parkinson’s disease, or degenerative diseases of the nervous system before or up to 1 month after vaccination were excluded.
The participants were followed up for a mean of 4.15 and 6.00 years after the first dose of the recombinant and live vaccines, respectively.
Taquet and team say that the “clinically meaningful” increase in time lived without dementia among individuals given the recombinant versus live vaccine was found in both women and men, although women were significantly more likely than men to remain diagnosis free, at 22% versus 13%.
They add that the results are “a particularly large effect size given that the live shingles vaccine is itself associated with a lower risk of dementia.”
Moreover, the increased dementia diagnosis-free time was consistent across dementia subcategories, with the exception of Lewy body and frontotemporal dementia. And the results were similar when analysis was restricted to those receiving the predominant vaccine, an exposure window of 6 months either side of the October 2017 vaccine change, only those receiving either vaccine rather than both, and after adjusting for socioeconomic deprivation.
In addition, the recombinant vaccine cohort was 35% less likely to have a herpes zoster infection within 6 years than the live vaccine cohort (RMTL, 0.65), with outcomes similar for men and women.
Finally, both vaccines were associated with a lower risk for dementia than the influenza and tetanus–diphtheria–pertussis (Tdap) vaccines (RMTL ratios, 0.73–0.86) also commonly given to this age group.
The reasons the shingles vaccines might protect against dementia “remain unclear,” say the study authors, although herpes infection has long been hypothesized as a risk factor for dementia, which may explain the superior dementia protection offered by the recombinant vaccine.
However, protection for both herpes and dementia after vaccination wanes over time, with hazard ratios for dementia protection falling from significantly lower than 1 in the first year to approaching and sometimes exceeding 1 in the years following, they add, which “could imply the vaccine delays, rather than prevents dementia onset.”
The investigators acknowledge the limitations of the observational study including those inherent to the use of electronic health record data and the fact that the impact of multiple vaccine doses was not investigated.
Nevertheless, they conclude that the robust results “provide a rationale for conducting a randomized control trial aiming to confirm the findings and inform future cost–effectiveness analysis of the recombinant vaccine.”
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