Antiherpetic medication and incident dementia: Observational cohort studies in four countries
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Abstract
Background and purpose: Several epidemiological studies from Taiwan, all using the same data resource, found significant associations between herpes virus infection, antiherpetic medication, and subsequent dementia. We conducted a multicenter observational cohort study using health registry data from Wales, Germany, Scotland, and Denmark to investigate potential associations between antiherpetic medication and incident dementia, and also to comprehensively investigate such associations broken down according to medication type and dose, type of herpes virus, and dementia subtype. Methods: A total of 2.5 million individuals aged 65 years or more were followed up using linked electronic health records in four national observational cohort studies. Exposure and outcome were classified using coded data from primary and secondary care. Data were analyzed using survival analysis with time‐dependent covariates. Results: Results were heterogeneous, with a tendency toward decreased dementia risk in individuals exposed to antiherpetic medication. Associations were not affected by treatment number, herpes subtype, dementia subtype, or specific medication. In one cohort, individuals diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk. Conclusions: Short‐term antiherpetic medication is not markedly associated with incident dementia. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic administration may reflect confounding and misclassification.
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Studies using electronic health records have found a link between VZV and risk of all-cause dementia, AD, vascular dementia, with antivirals decreasing all-cause dementia risk.
“Studies using electronic health records have found a link between VZV and risk of all-cause dementia, AD, vascular dementia, with antivirals decreasing all-cause dementia risk [23,36–40].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [38]
The Introduction reports studies linking VZV infection to incident dementia, and the Dementia incidence results find a small association between antiherpetic medication and lower dementia incidence in some cohorts. The paper does not establish a VZV-specific link to Alzheimer disease or vascular dementia: its findings for those subtypes concern medication exposure, not VZV infection. It also cautions in the Discussion that the medication association was heterogeneous and may reflect confounding, rather than a demonstrated reduction caused by antivirals. Page numbers were not provided in our copy. (LLM, conf=0.88)
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What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- Schnier, C., Janbek, J., Williams, L., Wilkinson, T., Laursen, T. M., Waldemar, G., Richter, H., Kostev, K., Lathe, R., & G Haas, J.
- Affiliations
- University of Edinburgh (GB)
- University of Copenhagen (DK)
- Aarhus University (DK)
- IQVIA (United Kingdom) (GB)
- Division of Infection Medicine University of Edinburgh Edinburgh United Kingdom
- Corresponding author
- Schnier, Christian
- ORCID
- Venue
- European Journal of Neurology
- Publisher
- Wiley
- Published
- 2021-03-19
- Volume
- 28
- Issue
- 6
- Pages
- 1840-1848
- ISSN
- 1351-5101 (ISSN-L)
- 1468-1331
- OpenAlex
- W3134069256
- Cited by
- 52
- References
- 4
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 16 · 2023: 6 · 2022: 10 · 2021: 5
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Neurology (publishedVersion, cc-by-nc)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- Funders
- Benter Foundation
- Medical Research Council (MR/P011349/1)
- Biotechnology and Biological Sciences Research Council (BB/K003801/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- dementia, herpesvirus infection, herpes simplex virus, antiviral agents, dementia risk, dementia subtypes, confounding, misclassification, older adults
- MeSH terms
- Dementia, Herpesviridae Infections, Humans, Registries, Risk Factors, Cohort Studies, Incidence
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