April 2, 2025 from GEN Edge News
A Natural Experiment with Big Implications
In a large, population-based study published in Nature, researchers led by Stanford Medicine found that older adults who received the shingles (zoster) vaccine were 20% less likely to develop dementia over a seven-year period. The study took advantage of a unique public health policy in Wales that made eligibility for the vaccine dependent on a person’s exact birthdate, creating what researchers called a “natural experiment.”
Dr. Pascal Geldsetzer, assistant professor of medicine at Stanford and lead author, explained that comparing people born just before and just after the eligibility cutoff date minimized bias:
“What makes the study so powerful is that it’s essentially like a randomized trial with control group—those a little bit too old to be eligible for the vaccine—and an intervention group—those just young enough to be eligible.”
Strong, Consistent Results
Researchers analyzed data from over 280,000 Welsh adults aged 71–88 who did not have dementia at the start of the program. Those just young enough to qualify for the vaccine were compared with those just too old to be eligible. This approach minimized confounding factors like lifestyle, education, or pre-existing health differences.
Over seven years, those who received the vaccine had a 3.5 percentage point lower chance of developing dementia — a 20% relative reduction.
“It was a really striking finding. This huge protective signal was there, any which way you looked at the data.”
said Geldsetzer.
The effect was especially strong in women, who may have stronger immune responses to vaccines and are more likely to develop shingles.
A Shift in the Dementia Research Landscape
The findings support a growing theory that viruses affecting the nervous system — like varicella zoster virus, which causes shingles — may play a role in the development of dementia. Traditionally, dementia research has focused on brain plaques and tangles associated with Alzheimer’s disease. But new thinking is shifting toward viral triggers and immune system interactions.
Dr. Anupam B. Jena, a Harvard professor who wrote an accompanying editorial in Nature, commented:
“The vaccine could represent a cost-effective intervention that has public-health benefits strongly exceeding its intended purpose.”
Next Steps: More Research and Possibly a Trial
The study only examined the older, live-attenuated version of the shingles vaccine, which has since been replaced by a newer protein-based version (Shingrix). Whether this newer vaccine has the same or stronger dementia-protective effect is still unknown.
Geldsetzer hopes to launch a randomized controlled trial using the older vaccine to establish a definitive causal relationship. He and his team have already replicated the findings in health record datasets from other countries, including Canada, England, Australia, and New Zealand, seeing the same strong protective effect.
Considering an IME or document review to resolve an insurance claim, legal file, or workplace health and safety issue?
Our specialists provide evidence-based opinions, so get in touch with Western Medical today to learn more about our services.