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Cited by 44Dementia and Cognitive Impairment ResearchHerpesvirus Infections and TreatmentsAlzheimer's disease research and treatments

Herpes Simplex Viral Infection Doubles the Risk of Dementia in a Contemporary Cohort of Older Adults: A Prospective Study

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Vestin, Erika, Boström, Gustaf, Olsson, Jan, Elgh, Fredrik, Lind, Lars, Kilander, Lena, Lövheim, Hugo, Weidung, Bodil·2024·Journal of Alzheimer’s Disease
DOI 10.3233/jad-230718PMC PMC10894565
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Abstract

Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer’s disease (AD). Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to anti-herpesvirus treatment and potential APOE ɛ4 carriership interaction. Methods: This study was conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001–2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied. Results: Cumulative AD and all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE ɛ4 or anti-CMV IgG. Similar results were obtained for HSV-1. Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.

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  • A link between HSV-1 seropositivity and AD has been found, and a recent prospective cohort study showed HSV-1 infection can double AD risk.

    “On the one hand, a link between HSV-1 seropositivity and AD has been found, and a recent prospective cohort study showed HSV-1 infection can double AD risk [25,26].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [26]

    The Introduction reports an association between HSV-1 and dementia risk and discusses associations between HSV seropositivity and AD or dementia risk. But the Discussion says this cohort found more than doubled incident dementia risk, not a statistically significant association with AD; its AD hazard ratio was similar in magnitude. Thus the claim substitutes AD risk for the study’s demonstrated dementia-risk finding. (LLM, conf=0.91)

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Cited by

Sorted by citations

Authors
Vestin, E., Boström, G., Olsson, J., Elgh, F., Lind, L., Kilander, L., Lövheim, H., & Weidung, B.
Affiliations
  • Uppsala University (SE)
  • Umeå University (SE)
Corresponding author
Weidung, Bodil
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2024-02-01
Volume
97
Issue
4
Pages
1841-1850
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-230718
PMC
PMC10894565
OpenAlex
W4391486491
Cited by
44
References
3
Citations by year
2026: 15 · 2025: 25 · 2024: 4
FWCI
12.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DiVA at Umeå University (Umeå University) (submittedVersion, cc-by)
  • Uppsala University Publications (Uppsala University) (submittedVersion, cc-by)
Funders
  • Demensförbundet
  • Umeå Universitet
  • Uppsala Universitet
  • Svenska Läkaresällskapet
  • Region Uppsala
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
herpes simplex virus, herpes simplex virus type 1
MeSH terms
Aged, Alzheimer Disease, Antibodies, Viral, Apolipoproteins E, Cytomegalovirus Infections, Herpes Simplex, Humans, Immunoglobulin G, Immunoglobulin M, Prospective Studies, Herpesvirus 1, Human

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