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Varicella-zoster virus reactivation and the risk of dementia
Vitaly Polisky, Maria Littmann, Aleksei Triastcyn, Max Horn, Andreas Georgiou, Robyn Widenmaier, Bruno Anspach, Halima Tahrat et al.. Nature Medicine, 2025-10-06
Topic: Risk, prevention and care in population studies
Varicella-zoster virus (VZV) is a neurotropic virus that establishes lifelong latency in humans. VZV reactivation is associated with a wide range of symptoms, including herpes zoster (HZ; also known as shingles), and has been implicated in the development of dementia, although to an unknown extent. Here we present a large-scale longitudinal analysis of health records from more than 100 million individuals in the United States that demonstrates a consistent relationship of VZV reactivation with dementia after controlling for nearly 400 measured characteristics (covering demographics, socioeconomic factors, comorbidities, medications, proxies for healthcare-seeking behavior, shifts in clinical guidelines and completeness of records). We found that recurrent HZ was associated with an increased risk of dementia compared to a single HZ episode. Additionally, exposure to HZ vaccines was associated with a reduced risk of dementia compared to the control 23-valent pneumococcal polysaccharide vaccine. Furthermore, the reduced risk of dementia after administration of the live-attenuated zoster vaccine waned over time and was highly correlated with a waning of the vaccine-mediated protection against HZ. The dementia risk reduction at 3 and 5 years postexposure was also stronger in individuals who received multiple as opposed to only one dose of the recombinant HZ vaccine and those at greater risk of HZ. Our findings strongly implicate VZV reactivation as a modifiable risk factor for dementia.
Key findings
- VZV reactivation is associated with a wide range of symptoms, including herpes zoster (HZ; also known as shingles), and has been implicated in the development of dementia, although to an unknown extent.
- We found that recurrent HZ was associated with an increased risk of dementia compared to a single HZ episode.
- Additionally, exposure to HZ vaccines was associated with a reduced risk of dementia compared to the control 23-valent pneumococcal polysaccharide vaccine.
- Our findings strongly implicate VZV reactivation as a modifiable risk factor for dementia.
Why it matters
In health records from more than 100 million individuals, recurrent herpes zoster was associated with increased dementia risk compared with a single episode, and exposure to herpes zoster vaccines was associated with reduced dementia risk compared with a control vaccine. The reduced risk after the live-attenuated zoster vaccine waned over time in line with waning protection against herpes zoster, and the authors say their findings strongly implicate varicella-zoster virus reactivation.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 63/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 42 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 26.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Patrick Schwab: h-index 17 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41053450) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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Read the original
- DOI: 10.1038/s41591-025-03972-5
- PubMed: 41053450
- Original source →
- Free full text: Nature Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Polisky, V., Littmann, M., Triastcyn, A., Horn, M., Georgiou, A., Widenmaier, R., et al. (2025). Varicella-zoster virus reactivation and the risk of dementia. Nature Medicine. https://doi.org/10.1038/s41591-025-03972-5
Vancouver
Polisky V, Littmann M, Triastcyn A, Horn M, Georgiou A, Widenmaier R, et al. Varicella-zoster virus reactivation and the risk of dementia. Nature Medicine. 2025. doi:10.1038/s41591-025-03972-5. PMID: 41053450.
BibTeX
@article{polisky2025-41053450,
author = {Polisky, Vitaly and Littmann, Maria and Triastcyn, Aleksei and Horn, Max and Georgiou, Andreas and Widenmaier, Robyn and Anspach, Bruno and Tahrat, Halima and others},
title = {{Varicella-zoster virus reactivation and the risk of dementia}},
journal = {Nature Medicine},
year = {2025},
doi = {10.1038/s41591-025-03972-5},
pmid = {41053450},
url = {https://doi.org/10.1038/s41591-025-03972-5}
}
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