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The recombinant shingles vaccine (Shingrix) was associated with a larger reduction in dementia risk than the live shingles vaccine (Zostavax), an analysis of more than 200,000 U.S. older adults showed.

Over a 6-year follow-up period, adults who predominantly received the recombinant herpes zoster vaccine had a 17% increase in time without a dementia diagnosis (restricted mean time lost ratio 0.83, 95% CI 0.80-0.87, P<0.0001) compared with those who received the live vaccine, reported Maxime Taquet, PhD, of the University of Oxford in England, and co-authors.

This translated into 164 additional days without a dementia diagnosis, Taquet and colleagues reported in . The reduction in dementia risk was present in both men and women, but greater in women.

The recombinant shingles vaccine also was tied to a lower risk of dementia compared with two other vaccines commonly used in older people -- influenza and tetanus/diphtheria/pertussis (Tdap) vaccines.

"The size and nature of this study makes these findings convincing, and should motivate further research," Taquet said in a statement.

"They support the hypothesis that vaccination against shingles might prevent dementia," he continued. "If validated in clinical trials, these findings could have significant implications for older adults, health services, and public health."

Several studies have linked viral illnesses with subsequent dementia. Human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) have been found in postmortem tissue samples of people with Alzheimer's disease at levels up to twice as high as non-Alzheimer's disease samples, for example.

Researchers also have suggested that herpes simplex virus 1 (HSV-1) coupled with an APOE4 gene may raise Alzheimer's risk considerably. Based on early HSV-1 research, a trial of the (Valtrex) in mild Alzheimer's disease is currently underway.

Last year, a preprint study in Wales suggested that the live shingles vaccine may be associated with a 20% reduction in dementia risk, with the relationship stronger in women than men.

"Although previous studies have suggested immunization against herpes viruses might protect against dementia, particularly in women, this took advantage of a change in vaccine type to overcome the many confounding variables that may have provided alternative explanations," noted Robert Howard, MD, of University College London, who wasn't involved with the new Oxford study.

"The next question is how does vaccination exert this dementia protection effect?" Howard on the U.K. Science Media Centre. "Is it through suppression of virus or is the induced immune response targeting a step in the molecular pathology of Alzheimer's disease?"

In the U.S., the in October 2017. In 2018, it received a preferential recommendation by the CDC's Advisory Committee on Immunization Practices (ACIP) over the live shingles vaccine. As of November 2020, the live shingles vaccine was , according to the CDC.

Taquet and co-authors used TriNetX electronic health records in the U.S. to study 103,837 individuals ages 65 and older who received a first dose of shingles vaccine between November 2017 and October 2020; 95% received the recombinant vaccine. These older adults were propensity-score matched with 103,837 individuals who received their first dose between October 2014 and September 2017 (98% had the live vaccine). People with previous diagnoses of dementia or neurodegenerative disease were excluded from the study.

Median follow-up was 4.15 years in the recombinant vaccine group, and 6.0 years in the live vaccine group. The primary outcome was a first diagnosis of dementia from 3 months (to exclude possible pre-existing dementia) to 6 years post-vaccination in a time-to-event analysis, based on ICD-10 codes.

Associations between recombinant shingles vaccination and dementia were consistent across dementia types except frontotemporal and Lewy body dementia. Older adults vaccinated after October 2017 also were less likely to have a herpes zoster infection post-vaccination.

The study was observational and cannot show causality, the researchers acknowledged. It relied on electronic health records, which may have had errors. Being diagnosis-free does not mean participants were disease-free, they pointed out.

Nonetheless, the findings are "intriguing and encouraging," said co-author Paul Harrison, FRCPsych, also of the University of Oxford. "Anything that might reduce the risk of dementia is to be welcomed, given the large and increasing number of people affected by it."

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