A nationwide analysis of electronic health records from more than 100 million US patients found that shingles vaccination may be associated with lower dementia incidence, whereas recurrent shingles increased dementia risk.
At 3 years following vaccination, investigators found that the patients who received the live-attenuated zoster vaccine had a 33% lower risk of dementia compared with those who received the 23-valent pneumococcal polysaccharide vaccine. The recombinant zoster vaccine, given in two doses, showed a 27% lower risk, and both associations persisted at 5 years.
Recurrent herpes zoster, caused by the reactivation of the varicella-zoster virus, was associated with an increased likelihood of dementia, particularly within the decade following the second shingles episode.
Vaccine protection varied across groups. Among female patients aged 50 years and older, dementia risk declined by roughly one-third with the live-attenuated vaccine at 3 years following the index date. In female patients aged 80 to 89 years who completed two recombinant vaccine doses, dementia incidence decreased by 39% at 3 years and 27% at 5 years. For the live-attenuated vaccine, the protective effects diminished over time, consistent with declining shingles immunity. The pneumococcal vaccine served as an active control since it targets a similar population but doesn't prevent shingles, reducing potential bias linked to health care behavior.
The investigators analyzed de-identified data from the Optum electronic health record database, which includes records from more than 7,000 hospitals and clinics between 2007 and 2023. Patients aged 50 years and older were included. One-to-one propensity-score matching accounted for nearly 400 baseline factors such as demographics, comorbidities, medications, and health care use. Dementia outcomes were compared among matched cohorts who received zoster or pneumococcal vaccines, and among those with recurrent shingles episodes. Sensitivity tests and temporal analyses were used to address residual confounding.
The study’s observational design limited causal interpretation. Possible misclassification of vaccination or dementia diagnoses may have occurred because of coding errors, and pharmacy data were incomplete. Follow-up for the recombinant vaccine was shorter due to its more recent introduction.
The investigators indicated that their findings supported further investigation into viral reactivation and its potential role in neurodegenerative disease pathways. They noted that the broader implications extended beyond individual vaccine protection. “Establishing [varicella-zoster virus] reactivation as a modifiable risk factor for progression to dementia could have wide implications for public health, prevention, and potential future development of dementia-targeting therapies,” said lead study author Vitaly Polisky, PhD, of GSK Biologicals SA. The investigators recommended long-term studies to determine whether preventing varicella-zoster virus reactivation could help delay or reduce dementia onset.
Full disclosures can be found in the published study.
Source: Nature Medicine
