Spotlight on the Shingles Vaccine—Again! - by Eric Topol

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News and Analyses<br>Spotlight on the Shingles Vaccine—Again!<br>Two new studies add to a remarkable body of evidence for benefit<br>Eric Topol<br>Jan 22, 2026

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Last April I wrote a Ground Truths entitled “The Shingles Vaccine and Reduction of Dementia.” At the time many were unaware of this unanticipated relationship based on 2 large natural experiments. Two new studies this week have advanced our understanding about the potential biological impact of the Shingles vaccine, independent of its effects for preventing Shingles or direct action vs. herpes zoster virus and reinforced its protection from dementia, ~80% of which is attributable to Alzheimer’s disease. In this post I won’t get into the details of what I previously wrote (please link back for more perspective), but instead devote the text to the new findings. I’ll come back to this summary Figure below shortly.

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A Fourth Natural Experiment: Canada

Today in Lancet Neurology, another Shingles vaccine natural experiment was reported that had unique features to help establish cause-and-effect for the vaccine (Zostavax, the live attenuated virus vaccine) and reduction of dementia. To be clear, a natural experiment is an observational study that is based on a naturally occurring situation or policy, such as a country’s policy for vaccine eligibility by birthdate. In many ways, these experiments can be considered better than randomized trials because there are no or minimal selection criteria, they are typically orders of magnitude larger with respect to number of individuals assessed, and they are real world rather than in context of a clinical trial which is subject to the— “Hawthorne effect’”—just being part of a study can have an impact.<br>In the new study of Canadians, the focus was on over 464,000 people aged 70 years and older who were enrolled in a primary care network; and the more than 250,000 from that group who were born in Ontario. The vaccine eligibility cutoff of birthdate before and after Jan 1, 1946 broke the groups from Ontario into two, for either being or not being vaccinated. With 5.5 years of follow-up, there was an absolute 2.0 per cent point reduction of dementia. Using a second date-of-birth eligibility (Jan 1, 1945) in Ontario, the findings were replicated. Using the same birth cohorts for Ontario compared with the other Canadian provinces that did not implement a Shingles vaccine program, as shown below, the differences for dementia reduction irons ere pronounced, increasing over the length of follow-up. This ability to triangulate by birthdates and to other parts of the country without a vaccine program is unique among the 4 natural experiments and helps to further support a cause-and-effect relationship.

Context With All Four Natural Experiments

Previously, there were natural experiments published for the country of Wales by Eyting et al (N=280,000), Australia by Pomirchy and colleagues (N-101,219), and a US comparison of the live attenuated vs recombinant (Shingrix) vaccine by Taquet et al (N=103,615). The numbers in parentheses refer to the number of people assessed, each analysis enabled by birthdate cutoffs. The reports from Wales, Australia and Canada all used the Zostavax (old) Shingles vaccine whereas the US study assessed the difference between recombinant Shingrix vs Zostavax with the main finding of a 17% increase in dementia-free time. All 4 of the reports included an in-depth analysis of potential confounders, showing, as you would expect, minimal differences between groups vaccinated or unvaccinated.<br>In the simplified Figure below, I’ve highlighted the consistent reduction in new dementia diagnosis during extended follow-up, along with the differences by sex with 3 of the 4 studies showing significantly greater impact in women. Notably, 3 of these publications were spearheaded by Pascal Geldsetzer at Stanford University.

A recent paper in Cell added another feature about the Shingles vaccine (Zostavax) drawn for the natural experiments. The vaccine not only helped prevent or delay mild cognitive impairment but also slowed the disease course among those with dementia, and reduced deaths attributable to dementia.

Share Ground Truths<br>Shingles Vaccine and Slowing of Biological Aging

In the Journal of Gerontology, Jung Ki Kim and colleagues from the University of Southern California, published a novel study of 3,884 participants, part of the US Health and Retirement study cohort, age 70+ (in 2016) for 7 domains of biology. Half (49.6%) had a Shingles vaccine. The 7 domains were: 1. adaptive immunity (biomarkers of B and T cells and their subtypes); 2. innate immunity (natural killer cells, other white blood cells besides lymphocytes); 3. Inflammation (IL-6, C-reactive protein, and 7 other blood inflammation markers); 4. epigenetic aging (PhenoAge, GrimAge, DundedinPACE); 5. Transcriptomic aging...