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Varicella-zoster virus reactivation and the risk of dementia.
Nat Med. 2025 Dec; 31(12):4172-4179.NMed

Abstract

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.

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Authors+Show Affiliations

Polisky V
GSK, Heidelberg, Germany.
Littmann M
GSK, Heidelberg, Germany.
Triastcyn A
GSK, Baar, Switzerland.
Horn M
GSK, Baar, Switzerland.
Georgiou A
GSK, Baar, Switzerland.
Widenmaier R
GSK, Toronto, Ontario, Canada.
Anspach B
GSK, Rockville, MD, USA.
Tahrat H
GSK, Rockville, MD, USA.
Kumar S
GSK, Collegeville, PA, USA.
Buser-Doepner C
GSK, Collegeville, PA, USA.
Geldsetzer P
Division of Primary Care and Population Health, Department of Medicine, Stanford University, Stanford, CA, USA. Chan Zuckerberg Biohub, San Francisco, CA, USA.
Van Duijn CM
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Schwab P
GSK, Baar, Switzerland. patrick.x.schwab@gsk.com.

MeSH

HumansDementiaHerpesvirus 3, HumanHerpes ZosterVirus ActivationMaleHerpes Zoster VaccineFemaleAgedMiddle AgedRisk FactorsLongitudinal StudiesUnited StatesAged, 80 and overAdult

Pub Type(s)

Journal Article

Language

eng

PubMed ID

41053450

Citation

Polisky, Vitaly, et al. "Varicella-zoster Virus Reactivation and the Risk of Dementia." Nature Medicine, vol. 31, no. 12, 2025, pp. 4172-4179.
Polisky V, Littmann M, Triastcyn A, et al. Varicella-zoster virus reactivation and the risk of dementia. Nat Med. 2025;31(12):4172-4179.
Polisky, V., Littmann, M., Triastcyn, A., Horn, M., Georgiou, A., Widenmaier, R., Anspach, B., Tahrat, H., Kumar, S., Buser-Doepner, C., Geldsetzer, P., Van Duijn, C. M., & Schwab, P. (2025). Varicella-zoster virus reactivation and the risk of dementia. Nature Medicine, 31(12), 4172-4179. https://doi.org/10.1038/s41591-025-03972-5
Polisky V, et al. Varicella-zoster Virus Reactivation and the Risk of Dementia. Nat Med. 2025;31(12):4172-4179. PubMed PMID: 41053450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Varicella-zoster virus reactivation and the risk of dementia. AU - Polisky,Vitaly, AU - Littmann,Maria, AU - Triastcyn,Aleksei, AU - Horn,Max, AU - Georgiou,Andreas, AU - Widenmaier,Robyn, AU - Anspach,Bruno, AU - Tahrat,Halima, AU - Kumar,Sanjay, AU - Buser-Doepner,Carolyn, AU - Geldsetzer,Pascal, AU - Van Duijn,Cornelia M, AU - Schwab,Patrick, Y1 - 2025/10/06/ PY - 2025/03/06/received PY - 2025/08/18/accepted PY - 2025/12/16/medline PY - 2025/10/7/pubmed PY - 2025/10/6/entrez SP - 4172 EP - 4179 JF - Nature medicine JO - Nat Med VL - 31 IS - 12 N2 - 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. SN - 1546-170X UR - https://www.unboundmedicine.com/medline/citation/41053450/full_citation DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓7 ↑52]

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