A large UK study compared those who took a shingles vaccine to those who took only flu or Tdap vaccines.
British investigators theorized that if the association of shingles with a subsequent diagnosis of dementia is causal, a reduction in risk would be expected in those vaccinated against VZV. Previous research has found that those receiving the original live-virus VZV vaccine (Zostavax) were less likely to subsequently develop dementia than those who did not receive the vaccine.
In this new study, the investigators examined the electronic health records of 200,000 people to assess the risk for developing AD or other dementias in people who received either the original live-virus vaccine (during the years it was offered) or the current and more effective recombinant vaccine (Shingrix) which replaced the original vaccine in 2017.
A multivariable analysis showed that in the 6 years following immunization the risk of subsequent dementia was 17% lower in those who received the current and more effective vaccine than in those who received the original vaccine.
The investigators then compared the risk of subsequent dementia in both of the two VZV vaccines to the risk of dementia in similar older individuals who had received the influenza vaccine or the tetanus–diphtheria–pertussis (Tdap) vaccine, but not a VZV vaccine. The risk in those who received the VZV vaccines was 14-27% (confidence interval) lower.
The risk reductions from the VZV vaccines were seen for Alzheimer’s disease and vascular dementia, but not seen for frontotemporal dementia or Lewy body dementia.
Growing evidence supports a role for infection with multiple different types of microbe in the pathogenesis of Alzheimer’s disease (AD) and other dementias. Among the microbes incriminated in several large studies are three herpesviruses: HSV-1, HSV-2 and VZV as well as SARS-CoV-2. Although a role for HHV-6 in the pathogenesis of AD has been proposed, this remains controversial (Komaroff 2020).
Observational studies that find associations between a risk factor (such as an infection) and an outcome (such as dementia) cannot establish causation. If the association is causal, one would expect that vaccination against or treatment of the agent would reduce the risk of subsequent dementia.
A previously reported large epidemiologic study showed a significantly increased risk of AD disease and other dementias in people who had been medically evaluated for herpes simplex virus infection (HSV-1 or HSV-2): (hazard ratio of 2.6, 95% CI: 2.2-2.8) (Tzeng 2018). That same study reported a second, astonishing finding: the risk of subsequent dementia in those people with HSV infection who had been treated with antivirals was 91% lower than the risk in those who had not been treated with antivirals (Tzeng 2018).
The new study, and the past large studies, are consistent with the hypothesis that vaccination against, or treatment of, infections with HSV-1, HSV-2 and VZV offers some protection against the subsequent development of dementia, suggesting that these viruses may be one trigger of the pathogenesis of dementias. Thus, it is plausible that HHV-6, too, might be capable of triggering dementia in some people, although the current evidence for that is weak.
Read the full article: Taquet 2024