New evidence suggests a link between shingles vaccination and a reduced risk of dementia, raising important questions about viral triggers, inflammation, and future prevention strategies.
Study: Recombinant shingles vaccine is associated with a reduced risk of dementia. Image Credit: Demi-point/Shutterstock
A recent study published in the journal Communications Nature found an association between the recombinant shingles vaccine (often called Shingrix) and a lower risk of dementia in adults aged 65 and older. The research, which analyzed health records of over 300,000 individuals, revealed that Shingrix was linked to a 51% lower observed risk of dementia within the study group. This finding is significant as dementia represents a growing global health crisis, and identifying potential preventative measures is crucial.
Specifically, researchers found that receiving two doses of the vaccine was associated with significantly lower risks of both Alzheimer’s disease and vascular dementia. These results remained consistent even after accounting for potential confounding factors, including the health status of those vaccinated, suggesting a genuine reduction in dementia risk that warrants further investigation.
The Burden of Dementia and Viral Hypotheses
Dementia is an umbrella term for a range of neurological conditions that progressively impair daily life. It is now a global public health crisis, affecting approximately 57.4 million people worldwide – a number projected to triple by 2050.
Despite decades of research, the causes of dementia remain complex. While age, genetics, lifestyle, and environmental factors are established risk factors, scientists have long suspected that the varicella-zoster virus (VZV), responsible for both chickenpox and shingles, may also play a role.
Studies have shown that reactivation of VZV in older adults causes shingles, a painful rash that has been linked to increased neuroinflammation and brain damage.
Data from earlier shingles vaccines, such as the live attenuated shingles vaccine (ZVL), also suggested a potential benefit in reducing dementia risk. However, evidence regarding the newer and more effective recombinant shingles vaccine has been limited until now.
Study Design, Population, and Bias Control
This study aimed to address this gap by conducting a retrospective cohort analysis using electronic health records from Kaiser Permanente Southern California. The goal was to examine the reduction in dementia risk, rather than prevention, reflecting the observational nature of the data.
The study population included 65,800 individuals aged 65 or older who received two doses of the recombinant shingles vaccine between April 2018 and December 2020, with an average follow-up of approximately 3.4 years. These individuals were matched in a 1:4 ratio to 263,200 unvaccinated peers based on age, sex, race, ethnicity, prior ZVL vaccination history, and extensive clinical variables. Follow-up began six months after vaccination to minimize misclassification errors related to pre-existing dementia.
The primary outcome was all-cause dementia, defined using International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes. Secondary outcomes included specific dementia subtypes such as Alzheimer’s disease, vascular dementia, and mild cognitive impairment (MCI).
Diagnostic validity was strengthened through targeted review of medical records for coded dementia and MCI cases.
To address potential healthy vaccinee bias, researchers compared the recombinant shingles vaccine recipients with a separate cohort of 65,800 people who received the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine. This comparison helped ensure that the vaccinated groups were similarly health-seeking, although some residual confounding cannot be entirely ruled out.
Observed Associations with Dementia and Cognitive Outcomes
The analyses showed that two doses of the recombinant shingles vaccine were associated with a 51% lower risk of dementia compared to being unvaccinated, with an adjusted hazard ratio of 0.49 and a 95% confidence interval of 0.46 to 0.51. The incidence rates of dementia were 10.74 per 1,000 person-years in the vaccinated group, compared to 23.04 in the unvaccinated group.
A stronger association was observed in women, with an adjusted hazard ratio of 0.45 compared to 0.55 in men. The results were otherwise consistent across all age groups and racial or ethnic categories, although the biological basis for the sex difference remains unclear.
Recombinant shingles vaccine administration was also associated with a 16% reduction in the risk of incident MCI, particularly among individuals followed for less than 3.5 years. Among those who developed MCI, vaccinated individuals experienced a longer median time to progression to dementia, with a median delay of approximately 68 days.
When compared directly with the Tdap vaccinated cohort, recombinant shingles vaccine recipients still had a 27% lower risk of dementia, reinforcing the persistence of the association after accounting for healthy vaccinee effects.
Interpretation, Mechanisms, and Implications for Research
This large, real-world observational study provides evidence that recombinant shingles vaccination is associated with a statistically significant reduction in dementia risk. However, causality cannot be established, and longer follow-up is needed given the slow progression of dementia.
The underlying biological mechanisms remain uncertain. The authors hypothesize that vaccination may reduce viral reactivation, which could otherwise trigger neuroinflammation or damage to brain blood vessels, contributing to progressive neurological decline.
Future research should investigate whether these cognitive associations are specific to the recombinant shingles vaccine, explore the optimal timing and dosage, and evaluate how shingles vaccination could be integrated into broader dementia risk reduction strategies. Longer longitudinal follow-up will be essential to clarify the durability and clinical relevance of these findings.
