Shingles vaccination and dementia: generation of cause-and-effect evidence

Using a series of natural experiments (published in Nature, Cell, JAMA, and The Lancet Neurology), Dr. Geldsetzer's group has generated a unique body of evidence that shingles vaccination has a protective effect on the development of dementia. In this research, he has been taking advantage of a natural randomization created by the date of birth-based eligibility rules for shingles vaccination that several countries have used. This allowed for a comparison of groups of individuals who differ in their age by just a few weeks but have a large difference in their probability of ever receiving shingles vaccination. The basic intuition of the power of this approach is that if one takes, at random, a thousand individuals born in one week and a thousand born just a week later, one would not expect any differences between them including in their health-related behaviors (e.g., diet and exercise). This avoids the common confounding concerns in more standard epidemiological studies. 

Dr. Geldsetzer believes that his group may have identified a one-off, inexpensive, off-patent, safe, and readily scalable tool for dementia prevention and, potentially, for the maintenance of neuroimmune health in older age more generally. His vision is to more conclusively test the effects of shingles vaccination for dementia prevention and treatment, and to generate insights into the mechanisms linking the vaccine to dementia. The ultimate goal of these efforts is to positively impact population health at scale and identify new directions for dementia disease drug and vaccine development. 

Pascal Geldsetzer is an Assistant Professor of Medicine at Stanford University and a Biohub Investigator. His research focuses on identifying and evaluating the most effective interventions for improving health at older ages. In addition to leading several randomized trials, his methodological emphasis lies on the use of natural experiments to ascertain causal effects in large observational datasets, particularly in electronic health record data. He has won an NIH New Innovator Award (in 2022), a Biohub investigatorship (in 2022), and three NIH R01 grants as Principal Investigator (in 2023 and 2024). In 2026, he was named one of the 100 most influential people in health and medicine globally by TIME Magazine (The TIME100 Health list) for his work on the link between shingles vaccination and dementia. He is currently trying to raise funds from philanthropy for a large-scale clinical trial of shingles vaccination for dementia prevention.

Some viruses that specifically target the nervous system, like certain herpesviruses, might contribute to dementia. This is because these viruses stay in the nervous system for life, cause inflammation, and reactivate as people age.

In the UK, the shingles vaccine was offered to certain people based on their date of birth. This created a situation where people born just days apart had very different chances of getting vaccinated but were otherwise bound to be similar. This is a crucial advantage compared to existing studies that have simply compared those who decide to get vaccinated (and are often more health-motivated and healthier) with those who do not. Taking advantage of this situation in health records from Wales, we found evidence that getting the shingles vaccine lowered the risk of developing dementia over seven years. This study was published in Nature. Our finding has since been confirmed by our group in different populations and settings.

In this project, he will attempt to leverage clinical trial data to more conclusively test this relationship and provide mechanistic insights.

"The MIND Prize will allow my group to take critical next steps in confirming and extending a unique body of evidence that we have never had before for a potential preventive tool for dementia."