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Cited by 368Herpesvirus Infections and TreatmentsCytomegalovirus and herpesvirus researchDementia and Cognitive Impairment Research

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections—a Nationwide, Population-Based Cohort Study in Taiwan

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Tzeng, Nian-Sheng, Chung, Chi-Hsiang, Lin, Fu-Huang, Chiang, Chien-Ping, Yeh, Chin-Bin, Huang, San-Yuan, Lu, Ru-Band, Chang, Hsin-An +7 more·2018·Neurotherapeutics
DOI 10.1007/s13311-018-0611-xPMC PMC5935641
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Abstract

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P < 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 [95% CI 0.079-0.108], P < 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations.

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  • HSV-2 seropositivity has been associated with decreased memory performance, but appeared to be unrelated to global cognition and other cognitive domains, or the risk of all-cause dementia, AD, vascular dementia and other dementias.

    “HSV-2 seropositivity has also been associated with decreased memory performance, but appeared to be unrelated to global cognition and other cognitive domains, or the risk of all-cause dementia, AD, vascular dementia and other dementias [27,28].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [28]

    The Results report that genital and non-genital HSV infections were associated with increased overall dementia risk, and that HSV infections were associated with increased risks of AD, vascular dementia, and other dementia—the opposite direction from the cited sentence’s dementia-risk claim. The Discussion says the study included HSV-1 or HSV-2 infections, but also says serology data were unavailable; it therefore does not directly test HSV-2 seropositivity. The paper reports no memory-performance or cognitive-domain finding. (LLM, conf=0.75)

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  • Antiherpetic treatment nearly eliminates the increased dementia risk after HSV infection.

    “This risk was nearly eliminated in patients that received antiherpetic treatment (Tzeng et al., 2018).”

    From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Tzeng et al., 2018

  • New HSV infection in people over 50 is associated with about a threefold increased risk of all-cause dementia.

    “One study demonstrated a significantly increased risk of developing all-cause dementia (~3-fold increase) in patients greater than 50 years of age following a new HSV infection.”

    From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Tzeng et al., 2018

  • The advent of acyclovir in the late 1980s considerably modified the prognosis of HSV-1 encephalitis.

    “The advent of acyclovir, in the late 1980s, considerably modified the prognosis of HSV-1 encephalitis [54–56].”

    From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [56]

  • Previous research has found that the development of anti-herpes medications had a positive impact, reducing the incidence of Alzheimer's disease.

    “Previous research has found that the development of anti-herpes medications had a positive impact, reducing the incidence of AD [56].”

    From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [56]

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1 retracted

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3 of the 67 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Tzeng NS, Chiang WS, Chen SY, et al. The Impact of Pharmacological Treatments on Cognitive Function and Severity of Behavioral Symptoms in Geriatric Elder Patients with Dementia: Pharmacological Treatments on in Elder Patients with Dementia. Taiwanese J Psychiatry. 2017;311:69-79.
  2. Daulatzai MA. Fundamental Role of Pan-Inflammation and Oxidative-Nitrosative Pathways in Neuropathogenesis of Alzheimer's Disease. Am J Neurodegener Dis. 2016;51:1-28.

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Authors
Tzeng, N.-S., Chung, C.-H., Lin, F.-H., Chiang, C.-P., Yeh, C.-B., Huang, S.-Y., Lu, R.-B., Chang, H.-A., Kao, Y.-C., Yeh, H.-W., Chiang, W.-S., Chou, Y.-C., Tsao, C.-H., Wu, Y.-F., & Chien, W.-C.
Affiliations
  • Tri-Service General Hospital (TW)
  • National Defense Medical Center (TW)
  • Tamkang University (TW)
Corresponding author
Chien, Wu-Chien
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2018-04
Volume
15
Issue
2
Pages
417-429
ISSN
1878-7479 (ISSN-L)
DOI
10.1007/s13311-018-0611-x
PMC
PMC5935641
OpenAlex
W2790037954
Cited by
356
References
67
Citations by year
2026: 34 · 2025: 35 · 2024: 41 · 2023: 40 · 2022: 49 · 2021: 59 · 2020: 48 · 2019: 29 · 2018: 21
FWCI
30.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Tri-Service General Hospital Research Foundation (TSGH-C105-130, TSGH-C106-002, TSGH-C107-004)
Topics
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
herpes simplex, dementia risk, antiviral therapy, neurodegeneration, Taiwan
MeSH terms
Aged, Antiviral Agents, Dementia, Female, Herpes Simplex, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Taiwan, Proportional Hazards Models

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