REVIEW OF: Eyting M et al, Nature 2025;641:438–446

STUDY TYPE: Prospective cohort study (natural experiment)

What is the connection between vaccines and dementia? Observational studies of influenza, pneumococcal, and shingles vaccines suggest lower dementia rates among vaccinated adults. But these findings are vulnerable to confounding, especially healthy-user bias, as people who get vaccinated tend to be healthier and more engaged in care to begin with. This study sidestepped that problem by taking advantage of a quirk in Wales: Adults born on or after September 2, 1933 were eligible for the live zoster vaccine (Zostavax), while those born just days earlier were not. That cutoff created two nearly identical groups differing mainly in vaccine eligibility.

Researchers followed 282,541 adults born between 1925 and 1942 for 7 years using electronic health records. They tracked new dementia diagnoses and examined dementia-related deaths using national mortality data.

Vaccine eligibility led to a 3.5 percentage point absolute reduction in dementia diagnoses, corresponding to a 20% relative reduction. The protective association was stronger in women, though vaccine effectiveness against shingles itself did not differ by sex. Population mortality data from England and Wales showed similar patterns, with vaccine eligibility associated with 1 fewer dementia-related death for every 20 cases over 9 years. That consistency across datasets makes it less likely the results are due to chance or confounding.

CARLAT TAKE

This study provides some of the strongest quasi-experimental evidence yet that preventing shingles might also lower dementia risk. The caveat: It looked at Zostavax, which has now been largely replaced by Shingrix, and we don’t know if the newer vaccine carries the same benefit. Still, when you’re recommending shingles vaccination to older adults, you can reasonably mention a possible long-term brain benefit. Just don’t promise quick cognitive dividends.