No evidence that herpes zoster is associated with increased risk of dementia diagnosis
Open accessAbstract
Objective: To investigate whether herpes zoster (HZ) was associated with subsequent increased risk of dementia diagnosis. Methods: We conducted a historical cohort study using primary care electronic health records from the Clinical Practice Research Datalink in the United Kingdom. Individuals with incident HZ aged ≥40 years from 2000 to 2017 were matched with up to four individuals without HZ by age, sex, primary care practise and calendar time. The primary outcome was a new diagnosis of all‐cause dementia. We used the Cox proportional hazards regression adjusting for demographic, lifestyle and clinical confounders to assess any association between HZ and dementia. We investigated interactions with sex, frailty index and antiviral treatment and conducted various sensitivity analyses. Results: The cohort comprised 177,144 individuals with HZ and 706,901 matched unexposed individuals (median age 65 years (IQR 55.1–75.0), 40% male) followed for a median duration of 4.6 years (IQR 2.0–8.1). In total, 26,585 (3%) patients had an incident dementia diagnosis recorded and 113,056 patients died (12.8%). HZ was associated with a small reduction in dementia diagnosis (adjusted HR 0.92 (95% CI 0.89–0.95)), occurring predominantly in frail individuals and females. For patients who were fit (578,115, 65%), no association was seen (adjusted HR 0.97, 95% CI 0.92–1.02). There was no association between HZ and a composite outcome of dementia or death (adjusted HR 1.00, 95% CI 0.99–1.02). Dementia risk did not vary by prescription of antiviral agents. Sensitivity analyses showed consistent results. Interpretation: HZ was not associated with increased dementia diagnosis in a UK primary care‐based cohort.
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Some studies have failed to find a link between VZV and AD, including those that utilize electronic health records or titer measurements.
“However, some studies have failed to find a link between VZV and AD, including those that utilize electronic health records or titer measurements [25,41,42].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [42]
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1 retracted
Dementia prevention, intervention, and care: 2020 report of the Lancet Commission
Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30367-6 · Cited by 10,430 · cited 1× · see citing works
“Only around 40% of dementia cases are potentially preventable by action on known modifiable risk factors.(3) Combined with the persistent failure of dementia treatment trials, this has prompted renewed urgency in the search for tractable dementia risk factors.”
BackgroundRetractedData Resource Profile: Clinical Practice Research Datalink (CPRD)
Herrett, E., Gallagher, A. M., Bhaskaran, K., Forbes, H., Mathur, R., van Staa, T., & Smeeth, L. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv098 · Cited by 2,667 · cited 1× · see citing works
“The CPRD Gold database contains anonymised primary care records from approximately 7% of the UK population who are broadly representative of the general population by age, sex and ethnicity.(16) Longitudinal records are generated through routine care and include demographic information, clinical events such as diagnos…”
MethodSelf-citationMicroglia in neurodegeneration
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Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study
Chen, V. C.-H., Wu, S.-I., Huang, K.-Y., Yang, Y.-H., Kuo, T.-Y., Liang, H.-Y., Huang, K.-L., & Gossop, M. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16m11312 · Cited by 142 · cited 2× · see citing works
“A small propensity score matched cohort from Taiwan (N = 3384) demonstrated a threefold increase in dementia risk after ophthalmic zoster,(11) but findings from two matched cohort studies using health insurance claims data from Taiwan and Korea suggested that any increased risk of dementia associated with HZ is likely…”
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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
- Warren‐Gash, C., Williamson, E., Shiekh, S. I., Borjas‐Howard, J., Pearce, N., Breuer, J. M., & Smeeth, L.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Department of Haematology University Medical Centre Groningen, University of Groningen Groningen The Netherlands
- University College London (GB)
- Corresponding author
- Warren‐Gash, Charlotte
- ORCID
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2022-02-16
- Volume
- 9
- Issue
- 3
- Pages
- 363-374
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC8935278
- OpenAlex
- W4213124747
- Cited by
- 31
- References
- 4
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 6
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (201440/Z/16/Z)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- herpes zoster, dementia, dementia risk, antiviral therapy, frailty, sex differences, mortality, primary care cohort
- MeSH terms
- Aged, Dementia, Female, Herpes Zoster, Humans, Male, Retrospective Studies, Risk Factors, Cohort Studies, Incidence
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