— Recombinant Shingles Vaccine Linked to 164 Days Free from Dementia Diagnosis

Key Points

• Those who received the recombinant shingles vaccine (Shingrix) saw a 17% longer duration without a dementia diagnosis compared to patients who got the live vaccine version.
• This extension translates to 164 more days on average without receiving a dementia diagnosis.
• The findings add to the growing understanding of a potential link between shingles vaccination and the prevention of dementia.

A recent analysis involving more than 200,000 U.S. seniors found that Shingrix, the recombinant shingles vaccine, was more effective at reducing dementia risk than the older live vaccine, Zostavax.

During a six-year follow-up, adults who mainly received Shingrix experienced a 17% increase in time lived without a dementia diagnosis (restricted mean time lost ratio 0.83, 95% CI 0.80-0.87, P<0.0001). This is compared to individuals who received Zostavax, according to lead researcher Maxime Taquet, PhD, from the University of Oxford, and colleagues.

This advantage equated to an additional 164 dementia-free days, the team reported in their publication in Nature Medicine. The observed reduction in dementia risk was present across both genders but appeared more pronounced in women.

Additionally, the recombinant vaccine was associated with a lower dementia risk compared to frequently administered vaccines for older adults, including the flu and tetanus/diphtheria/pertussis (Tdap) vaccines.

"Given the scope of this study, these results are compelling and should encourage further exploration into this area," said Taquet in a press release, adding that "the data supports the theory that shingles vaccination may play a role in preventing dementia."

If subsequent clinical trials validate these findings, it could have profound effects on public health strategies for seniors, including the promotion of this vaccine for dementia prevention."

Past research has drawn connections between viral infections and dementia risk. For example, increased presence of human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) has been detected in postmortem brain samples of Alzheimer’s patients, at rates significantly higher than those who did not have the disease.

Similarly, studies have suggested that infection with herpes simplex virus 1 (HSV-1), coupled with the APOE4 gene, could significantly raise Alzheimer’s risk. Based on such insights, there’s an ongoing trial evaluating the antiviral drug valacyclovir (Valtrex) for mild Alzheimer’s cases.

Research conducted in Wales last year hinted that the live shingles vaccine could reduce dementia risk by 20%, with a stronger effect seen in women than men.

"Earlier research pointed to vaccines for herpes viruses offering a protective effect against dementia, particularly in women," remarked Robert Howard, MD, of University College London, commenting on the new Oxford study. "This study leverages a change in vaccine formulations, which helps mitigate confounding factors," Howard added.

He posed the question, "How exactly does vaccination provide this protection against dementia? Is it through direct suppression of viral pathogens, or does the immune response specifically interrupt a key molecular process involved in Alzheimer’s disease pathology?"

In the U.S., Shingrix was officially approved in October 2017 and received favorable recommendations in 2018 from the CDC's Advisory Committee on Immunization Practices (ACIP), overtaking the live shingles vaccine. By November 2020, Zostavax was no longer available, per the CDC.

To conduct their study, Taquet and his collaborators utilized TriNetX electronic health records from U.S. patients. They specifically looked at data from 103,837 individuals aged 65 and older, who were administered their first shingles vaccine dose between November 2017 and October 2020—95% of whom had received Shingrix. These participants were compared to a similar cohort of 103,837 older adults who were given their vaccine between October 2014 and September 2017—98% of whom were given Zostavax. Individuals with prior dementia or neurodegenerative disease diagnoses were excluded from the analysis.

The median follow-up period was 4.15 years in the recombinant vaccine group versus 6.0 years in the live vaccine group. The primary outcome under study was the first diagnosis of dementia occurring from 3 months (to avoid misclassifying pre-existing cases) up to 6 years post-vaccination, tracked using ICD-10 codes in the health records.

Interestingly, the association between dementia risk reduction and receiving the recombinant shingles vaccine held true across most dementia types, with the exception of frontotemporal and Lewy body dementias. Additionally, older adults vaccinated after October 2017 with Shingrix saw fewer herpes zoster infections following vaccination.

The study’s authors acknowledged their research's observational nature, which cannot determine causation. Data depended on electronic health records, which may contain inaccuracies. Additionally, being free from a diagnosis doesn’t guarantee an absence of disease, they emphasized.

Nonetheless, the outcome is "both intriguing and encouraging," according to co-author Paul Harrison, FRCPsych, also from the University of Oxford. "Any intervention that might reduce dementia risk deserves serious attention, given how widespread and growing this problem is," he said.

Disclosures

The study was funded by the NIHR Oxford Health Biomedical Research Centre.

Neither Taquet nor Harrison reported any ties to relevant industries. However, one of their co-authors has served as a consultant for GSK, the pharmaceutical company behind Shingrix. GSK was not informed of the study until after its publication was confirmed.

Dr. Robert Howard reported no relevant conflicts of interest.

Primary Source

Nature Medicine

Source Reference: Taquet M, et al "The recombinant shingles vaccine is associated with lower risk of dementia" Nat Med 2024; DOI: 10.1038/s41591-024-03201-5.