Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study
Abstract
OBJECTIVE: Some infectious diseases have been found to be associated with cognitive impairment and dementia. However, the relationship between herpes zoster and dementia has received little attention. This study aimed to investigate this association as well as associations of antiviral treatments for herpes zoster and incident dementia using a large national sample. METHODS: Cases were identified from the Taiwan National Health Insurance Research Database with a new diagnosis of herpes zoster (ICD-9-CM code: 053) between 1997 and 2013. Each identified individual with a case of herpes zoster was compared with 1 sex-, age-, and residence-matched control subject. Both groups were followed until the first diagnosis of dementia (ICD-9-CM codes: 290.0 to 290.4, 294.1, 331.0 to 331.2, and 331.82), withdrawal from the registry, or the end of 2013. Cox regression analyses and competing risk model were applied, adjusting for sex, age, residence, depression, autoimmune disease, ischemic stroke, traumatic brain injury, alcohol use disorder, and antiviral treatments for herpes zoster to evaluate the risk of interest. RESULTS: A total of 39,205 cases with herpes zoster were identified. Of the 78,410 study and comparison subjects, 4,204 were diagnosed as having dementia during a mean (SD) follow-up period of 6.22 (4.05) years. Herpes zoster was associated with a slightly increased risk of dementia in the fully adjusted model (hazard ratio [HR] = 1.11; 95% CI, 1.04-1.17). Prescriptions of antiviral therapy were associated with a reduced risk of developing dementia following the diagnosis of herpes zoster (HR = 0.55; 95% CI, 0.40-0.77). CONCLUSIONS: Herpes zoster was associated with an increased risk of dementia, independent of potential confounding factors. Antiviral treatment might be protective in preventing dementia in patients with herpes zoster.
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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 [37]
Zoster infection is associated with a very slight increased risk of all-cause dementia (HR 1.12).
“A second study demonstrated a very slight increased risk of developing all-cause dementia after zoster infection (HR 1.12).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Chen et al., 2018
Antiherpetic treatment after zoster infection is associated with decreased dementia risk (HR 0.47).
“Again, a significant decrease in dementia risk was observed in patients that received antiherpetic treatment (HR 0.47) (Chen et al., 2018).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Chen et al., 2018
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Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper
Molero, J., Moreno, S., Rodríguez‐Artalejo, F., Ruiz‐Galiana, J., Cantón, R., Ramos, P. D. L., Botella, A. G., García‐Lledó, A., Hernández‐Sampelayo, T., Gómez‐Pavón, J., et al. (2023) · Revista Española de Quimioterapia · doi:10.37201/req/004.2023 · Cited by 20 · see citing works
Update on modifiable risk factors for Alzheimer’s disease and related dementias
Jaisa-aad, M., Muñoz-Castro, C., & Serrano-Pozo, A. (2024) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001243 · Cited by 17 · see citing works
Wang, Y., Song, X., Wang, Y., Huang, L., Luo, W., Li, F., Qin, S., Wang, Y., Xiao, J., Wu, Y., et al. (2020) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2020.1794789 · Cited by 21 · see citing works
Eckerström, M., Nilsson, S., Zetterberg, H., Blennow, K., & Grahn, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-79800-2 · Cited by 20 · see citing works
Charonis, S. A., James, L. M., & Georgopoulos, A. P. (2020) · Current Research in Translational Medicine · doi:10.1016/j.retram.2020.06.002 · Cited by 21 · see citing works
Lee, M., Huang, C., Chen, Y., Yang, Y., & Chen, V. C. (2020) · International Journal of Cancer · doi:10.1002/ijc.33307 · Cited by 20 · see citing works
“Data from this database have been used in many epidemiological studies in Taiwan.22,23”
MethodSelf-citationFrancesco, M. A. D. (2024) · Viruses · doi:10.3390/v16010133 · Cited by 22 · see citing works
“Patients with herpes zoster showed a significantly increased risk of developing AD Retrospective cohort studies [95,96] Studies showed an association between CMV and moderate–severe dementia Population cohort study [99] HSV-1 Seroprevalence study [104] CMV, EBV, and HHV-6-infected patients shared…”
BackgroundInfluentialGao, J., Feng, L., Wu, B., Xia, W., Xie, P., Ma, S., Liu, H., Meng, M., & Sun, Y. (2023) · Neurological Sciences · doi:10.1007/s10072-023-07038-7 · Cited by 19 · see citing works
“Two epidemiological studies conducted in Taiwan of China, using the same data sources, showed that herpes-virus infection is associated with dementia [21, 27].”
InfluentialBernstein, H., Keilhoff, G., Dobrowolny, H., et al. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-019-00995-1 · Cited by 18 · see citing works
Symptomatic Herpes Simplex Virus Infection and Risk of Dementia in US Veterans: a Cohort Study
Young‐Xu, Y., Powell, E. I., Zwain, G., Yazdi, M. T., Gui, J., & Shiner, B. R. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01084-9 · Cited by 18 · see citing works
Infectious Disease as a Modifiable Risk Factor for Dementia: A Narrative Review
Farrer, T. J., Moore, J. D., Chase, M., Gale, S. D., & Hedges, D. W. (2024) · Pathogens · doi:10.3390/pathogens13110974 · Cited by 17 · see citing works
“In a large population sample in Taiwan, Chen et al. (2018) [92], while identifying a slightly increased risk of dementia among those with herpes zoster (shingles) (HR: 1.11; 95% CI: 1.04–1.17), also demonstrated that individuals prescribed antiviral therapy were at a decreased risk of dementia (HR:…”
InfluentialBubak, A. N., Beseler, C. L., Como, C. N., Coughlan, C. M., Johnson, N. R., Hassell, J. E., Blackmon, A. M., Mescher, T., Schmid, D. S., Coleman, C., et al. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa513 · Cited by 17 · see citing works
Recombinant zoster vaccine is associated with a reduced risk of dementia
Rayens, E. A., Sy, L. S., Qian, L., Ackerson, B. K., Tubert, J. E., Luo, Y., Modha, P. P., Calderon, R., Chmielewski-Yee, E., Oraichi, D., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-69289-0 · Cited by 16 · see citing works
Shinomoto, M., Kasai, T., Tatebe, H., et al. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-020-00227-w · Cited by 14 · see citing works
“Similar results have also been observed in varicella zoster virus (VZV) infections [3].”
ResultBubak, A. N., Beseler, C. L., Como, C. N., Tyring, S. K., Haley, C. T., Mescher, T., Hassell, J. E., Cohrs, R. J., Potter, H., & Nagel, M. A. (2020) · Journal of NeuroVirology · doi:10.1007/s13365-020-00830-7 · Cited by 15 · see citing works
Yeh, J.-Y., Hou, T.-Y., Tseng, W.-T., Chen, V. C.-H., Yang, Y.-H., Kuo, T.-Y., Weng, J.-C., Lee, C. T.-C., Chen, Y.-L., & Lee, M.-J. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s242153 · Cited by 14 · see citing works
“The database has been used in numerous epidemiologic studies.(28,29)”
MethodSelf-citationPotential Role for Herpesviruses in Alzheimer’s Disease
Duggan, M. R., Torkzaban, B., Ahooyi, T. M., & Khalili, K. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200814 · Cited by 13 · see citing works
Alzheimer's disease and herpes viruses: Current events and perspectives
Pinchera, B., Filippo, I. D., Cuccurullo, F., Salvatore, E., & Gentile, I. (2024) · Reviews in Medical Virology · doi:10.1002/rmv.2550 · Cited by 13 · see citing works
Chen, V. C., Yang, Y., Kuo, T., Lu, M., Tseng, W., Hou, T.-Y., Yeh, J.-Y., Lee, C. T., Chen, Y., Lee, M., et al. (2020) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796020000608 · Cited by 13 · see citing works
“The database has been used in many epidemiologic studies in Taiwan (Lee et al ., 2017; Chen et al ., 2018).”
MethodSelf-citationStructural and mechanistic insights into herpesvirus helicase–primase and its therapeutic inhibitors
Yao, Q., Mercier, A., Nayak, A., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-02168-4 · Cited by 12 · see citing works
“…hosts, causing a wide spectrum of life-threatening sequelae (for example, encephalitis and pneumonitis) 2,3 , while a growing body of evidence points towards an association between these pathogens and an increased risk of dementia in older adults, including Alzheimer’s disease 4–7 .”
Herpes simplex virus infection and the risk of dementia: a systematic review and meta-analysis
Elhalag, R. H., Motawea, K. R., Talat, N. E., Rouzan, S. S., Mahmoud, N., Hammad, E. M., Reyad, S. M., Mohamed, M., & Shah, J. (2023) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000000951 · Cited by 10 · see citing works
Weinmann, S. A., Rawlings, A. M., Koppolu, P., Rosales, A. G., Prado, Y. K., & Schmidt, M. A. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296957 · Cited by 11 · see citing works
Yoshikane, A., Miura, H., Shima, S., et al. (2024) · Emerging infectious diseases · doi:10.3201/eid3012.240538 · Cited by 10 · see citing works
Common infections and neuroimaging markers of dementia in three UK cohort studies
Green, R., Sudre, C. H., Warren‐Gash, C., Butt, J., Waterboer, T., the Insight 46 study team, Hughes, A. D., Schott, J. M., Richards, M., Chaturvedi, N., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13613 · Cited by 9 · see citing works
Thapa, S., Shah, S., Bhattarai, A., Panah, M. Y., Chand, S., & Mirmosayyeb, O. (2024) · Health Science Reports · doi:10.1002/hsr2.1941 · Cited by 10 · see citing works
“2,9 The VZV is a neurotrophic virus that lies dormant in the sensory ganglia.”
BackgroundInfluentialHerpes zoster and long-term risk of subjective cognitive decline
Yeh, T., Curhan, G. C., Yawn, B. P., Willett, W. C., & Curhan, S. G. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01511-x · Cited by 13 · see citing works
“Some studies also suggest that antiviral treatment may reduce the risk of dementia among individuals who had HZ [7, 37].”
BackgroundHerpes Infections and Dementia: Rebutting Alternative Fact
Lathe, R., Tzeng, N., & Itzhaki, R. F. (2019) · Neurotherapeutics · doi:10.1007/s13311-018-00700-5 · Cited by 9 · see citing works
Mayburd, A. L., Koivogui, M., & Baranova, A. V. (2019) · PLoS ONE · doi:10.1371/journal.pone.0224315 · Cited by 9 · see citing works
Zhang, Y., Liu, W., & Yang, X. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1471736 · Cited by 11 · see citing works
“Notably, despite being a conference abstract, Chen et al. (23) provided the required data for analysis and was included to collect a larger number of studies.”
Marra, F., Gomes, K., Liu, E., Vadlamudi, N. K., Richardson, K., & Cragg, J. J. (2025) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2025.2546741 · Cited by 13 · see citing works
“31,32,34,36 There was an estimated 16% reduction in the risk of dementia (RR 0.84; 95% CI: 0.71, 0.99, I 2 = 73%).”
InfluentialDoes antiherpetic antiviral therapy reduce the risk of dementia?
Itzhaki, R. F. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00596-4 · Cited by 9 · see citing works
Olson, M. N., Dawes, P., Murray, L. F., Barton, N., Sundstrom, J., Orszulak, A. R., Chigas, S. M., Tran, K., Aylward, A. J., Caliandro, M. F., et al. (2026) · npj Dementia · doi:10.1038/s44400-026-00066-y · Cited by 7 · see citing works
- Authors
- Chen, V. C.-H., Wu, S.-I., Huang, K.-Y., Yang, Y.-H., Kuo, T.-Y., Liang, H.-Y., Huang, K.-L., & Gossop, M.
- Affiliations
- Chang Gung University (TW)
- Mackay Memorial Hospital (TW)
- Ministry of Health and Welfare (TW)
- National Taiwan University (TW)
- Chang Gung Memorial Hospital (TW)
- King's College London (GB)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2018-02-21
- Volume
- 79
- Issue
- 1
- Pages
- 16m11312
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2773840635
- Cited by
- 142
- References
- 0
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 20 · 2023: 13 · 2022: 20 · 2021: 21 · 2020: 21 · 2019: 14 · 2018: 3
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- 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, antiviral therapy, cognitive impairment, dementia risk, neurodegeneration
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Antiviral Agents, Dementia, Female, Herpes Zoster, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Sex Factors, Taiwan, Cohort Studies, Comorbidity, Incidence, Proportional Hazards Models, Case-Control Studies
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