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The association between varicella zoster virus and dementia: a systematic review and meta-analysis of observational studies

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Abstract

Purpose

The relationship between varicella zoster virus (VZV) infection and the risk of dementia has not been previously studied specifically. Therefore, this study sought to determine the relationship between studying VZV infection and dementia occurring in the general population by conducting an extensive meta-analysis of published cases.

Method

A systematic literature search was conducted in seven online databases by October 31, 2022. Heterogeneity was tested by the I2 index. Pooled HR and 95% CI were used to estimate the effect of VZV infection on dementia. Sensitivity analyses and publication bias were also performed.

Result

Nine studies involving 3,326,673 subjects were included. VZV infection was associated with an increased risk of dementia (HR = 1.11, 95% CI: 1.02–1.21). The risk of dementia was reduced in those who received antiviral therapy compared to those who did not (HR = 0.84, 95% CI: 0.71–0.99). In addition, VZV infection was found to be associated with an increased risk of developing dementia in the pooled results of the moderate quality study (HR = 1.81,95% CI: 1.27–2.59), and this association persisted when subgroup analyses were performed based on region (Asia: HR = 1.18,95% CI: 1.04–1.33).

Conclusions

Our results suggest that VZV infection might increase the risk of developing dementia, but there is no clear mechanism about the true relationship, and since there is no effective treatment for dementia, and our results suggest that some populations can benefit from antiviral therapy, it is at least arguable that patients who develop VZV infection should be treated with appropriate antiviral medications.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Melesie G, Dinsa H (2013) A literature review on: pathogenesis and management of dementia due to Alzheimer disease. Bio Genet J 1:18–31

  2. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9(1):63-75.e2. https://doi.org/10.1016/j.jalz.2012.11.007

    Article  PubMed  Google Scholar 

  3. Gale SA, Acar D, Daffner KR (2018) Dementia. Am J Med 131(10):1161–1169. https://doi.org/10.1016/j.amjmed.2018.01.022

    Article  PubMed  Google Scholar 

  4. Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 322(7300):1447–1451. https://doi.org/10.1136/bmj.322.7300.1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gorelick PB (2004) Risk factors for vascular dementia and Alzheimer disease. https://doi.org/10.1161/01.STR.0000143318.70292.47

  6. Newman AB, Fitzpatrick AL, Lopez O, Jackson S, Lyketsos C, Jagust W, Ives D, Dekosky ST, Kuller LH (2005) Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 53(7):1101–1107. https://doi.org/10.1111/j.1532-5415.2005.53360.x

    Article  PubMed  Google Scholar 

  7. Vagnucci AJ, Li WW (2003) Alzheimer’s disease and angiogenesis. Lancet 361(9357):605–608. https://doi.org/10.1016/S0140-6736(03)12521-4

    Article  CAS  PubMed  Google Scholar 

  8. Pinchinat S, Cebrián-Cuenca AM, Bricout H, Johnson RW (2013) Similar herpes zoster incidence across Europe: results from a systematic literature review. Bmc Infect Dis 13:170. https://doi.org/10.1186/1471-2334-13-170

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kleinschmidt-DeMasters BK, Gilden DH (2001) The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol 11(4):440–451. https://doi.org/10.1111/j.1750-3639.2001.tb00413.x

    Article  CAS  PubMed  Google Scholar 

  10. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA (2009) Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 8(8):731–740. https://doi.org/10.1016/S1474-4422(09)70134-6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gilden DH, Lipton HL, Wolf JS, Akenbrandt W, Smith JE, Mahalingam R, Forghani B (2002) Two patients with unusual forms of varicella-zoster virus vasculopathy. N Engl J Med 347(19):1500–1503. https://doi.org/10.1056/NEJMoa020841

    Article  PubMed  Google Scholar 

  12. Nagel MA, Gilden D (2014) Update on varicella zoster virus vasculopathy. Curr Infect Dis Rep 16(6):407. https://doi.org/10.1007/s11908-014-0407-z

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bandeira F, Roizenblatt M, Levi GC, Freitas D, Belfort RJ (2016) Herpes zoster ophthalmicus and varicella zoster virus vasculopathy. Arq Bras Oftalmol 79(2):126–129. https://doi.org/10.5935/0004-2749.20160038

    Article  PubMed  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  15. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  16. Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280(19):1690–1691. https://doi.org/10.1001/jama.280.19.1690

    Article  CAS  PubMed  Google Scholar 

  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  18. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. https://doi.org/10.1002/sim.1186

    Article  PubMed  Google Scholar 

  19. Haidich AB (2010) Meta-analysis in medical research. Hippokratia 14(Suppl 1):29–37

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  21. Chen VCH, Wu SI, Huang KY, Yang YH, Kuo TY, Liang HY, Huang KL, Gossop M (2018) Herpes zoster and dementia: A nationwide population-based cohort study. J Clin Psychiat 79(1) https://doi.org/10.4088/JCP.16m11312

  22. Omland LH, Vestergaard HT, Dessau RB, Bodilsen J, Andersen NS, Christiansen CB, Ellermann-Eriksen S, Nielsen L, Andersen C, Lebech AM, Obel N (2021) Characteristics and Long-term Prognosis of Danish Patients with Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared with the Background Population. J Infect Dis 224(5):850–859. https://doi.org/10.1093/infdis/jiab013

    Article  CAS  PubMed  Google Scholar 

  23. Shim Y, Park M, Kim J (2022) Increased incidence of dementia following herpesvirus infection in the Korean population. Medicine (United States) 101(41):E31116. https://doi.org/10.1097/MD.0000000000031116

    Article  Google Scholar 

  24. Lopatko Lindman K, Hemmingsson ES, Weidung B, Brännström J, Josefsson M, Olsson J, Elgh F, Nordström P, Lövheim H (2021) Herpesvirus infections, antiviral treatment, and the risk of dementia—a registry-based cohort study in Sweden. Alzheimer's: Transl Res Clin Interv 7(1) https://doi.org/10.1002/trc2.12119

  25. Schnier C, Janbek J, Williams L, Wilkinson T, Laursen TM, Waldemar G, Richter H, Kostev K, Lathe R, Haas JG (2021) Antiherpetic medication and incident dementia: Observational cohort studies in four countries. Eur J Neurol 28(6):1840–1848. https://doi.org/10.1111/ene.14795

    Article  PubMed  Google Scholar 

  26. Schmidt SAJ, Veres K, Sørensen HT, Obel N, Henderson VW (2022) (2022) Incident Herpes Zoster and Risk of Dementia: A Population-Based Danish Cohort Study. Neurology 99(7):E660–E668. https://doi.org/10.1212/WNL.0000000000200709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tsai MC, Cheng WL, Sheu JJ, Huang CC, Shia BC, Kao LT, Lin HC (2017) Increased risk of dementia following herpes zoster ophthalmicus. Plos One 12(11):e0188490. https://doi.org/10.1371/journal.pone.0188490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Warren-Gash C, Williamson E, Shiekh SI, Borjas-Howard J, Pearce N, Breuer JM, Smeeth L (2022) No evidence that herpes zoster is associated with increased risk of dementia diagnosis. Ann Clin Transl Neur 9(3):363–374. https://doi.org/10.1002/acn3.51525

    Article  Google Scholar 

  29. Lophatananon A, Mekli K, Cant R, Burns A, Dobson C, Itzhaki R, Muir K (2021) Shingles, Zostavax vaccination and risk of developing dementia: A nested case-control study - Results from the UK Biobank cohort. Bmj Open 11(10) https://doi.org/10.1136/bmjopen-2020-045871

  30. Tzeng NS, Chung CH, Lin FH, Chiang CP, Yeh CB, Huang SY, Lu RB, Chang HA, Kao YC, Yeh HW, Chiang WS, Chou YC, Tsao CH, Wu YF, Chien WC (2018) Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan. Neurotherapeutics 15(2):417–429. https://doi.org/10.1007/s13311-018-0611-x

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bae S, Yun SC, Kim MC, Yoon W, Lim JS, Lee SO, Choi SH, Kim YS, Woo JH, Kim SY, Kim SH (2021) Association of herpes zoster with dementia and effect of antiviral therapy on dementia: a population-based cohort study. Eur Arch Psy Clin N 271(5):987–997. https://doi.org/10.1007/s00406-020-01157-4

    Article  Google Scholar 

  32. Bubak AN, Como CN, Hassell JJ, Mescher T, Frietze SE, Niemeyer CS, Cohrs RJ, Nagel MA (2022) Targeted RNA Sequencing of VZV-Infected Brain Vascular Adventitial Fibroblasts Indicates That Amyloid May Be Involved in VZV Vasculopathy. Neurol Neuroimmunol Neuroinflamm 9(1) https://doi.org/10.1212/NXI.0000000000001103.

  33. Bubak AN, Como CN, Coughlan CM, Johnson NR, Hassell JE, Mescher T, Niemeyer CS, Mahalingam R, Cohrs RJ, Boyd TD, Potter H, Russ HA, Nagel MA (2020) Varicella-Zoster Virus Infection of Primary Human Spinal Astrocytes Produces Intracellular Amylin, Amyloid-β, and an Amyloidogenic Extracellular Environment. J Infect Dis 221(7):1088–1097. https://doi.org/10.1093/infdis/jiz560

    Article  CAS  PubMed  Google Scholar 

  34. Cairns DM, Itzhaki RF, Kaplan DL (2022) Potential Involvement of Varicella Zoster Virus in Alzheimer’s Disease via Reactivation of Quiescent Herpes Simplex Virus Type 1. J Alzheimers Dis 88(3):1189–1200. https://doi.org/10.3233/JAD-220287

    Article  CAS  PubMed  Google Scholar 

  35. Li Q, Ali MA, Cohen JI (2006) Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell 127(2):305–316. https://doi.org/10.1016/j.cell.2006.08.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bernstein HG, Keilhoff G, Dobrowolny H, Steiner J (2020) Binding varicella zoster virus: an underestimated facet of insulin-degrading enzyme´s implication for Alzheimer´s disease pathology? Eur Arch Psychiatry Clin Neurosci 270(4):495–496. https://doi.org/10.1007/s00406-019-00995-1

    Article  PubMed  Google Scholar 

  37. Wang JP, Kurt-Jones EA, Shin OS, Manchak MD, Levin MJ, Finberg RW (2005) Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2. J Virol 79(20):12658–12666. https://doi.org/10.1128/JVI.79.20.12658-12666.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Haanpää M, Dastidar P, Weinberg A, Levin M, Miettinen A, Lapinlampi A, Laippala P, Nurmikko T (1998) CSF and MRI findings in patients with acute herpes zoster. Neurology 51(5):1405–1411. https://doi.org/10.1212/wnl.51.5.1405

    Article  PubMed  Google Scholar 

  39. Bardach AE, Palermo C, Alconada T, Sandoval M, Balan DJ, Nieto GJ, Gómez J, Ciapponi A (2021) Herpes zoster epidemiology in Latin America: A systematic review and meta-analysis. Plos One 16(8):e0255877. https://doi.org/10.1371/journal.pone.0255877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Itzhaki RF, Lathe R (2018) Herpes Viruses and Senile Dementia: First Population Evidence for a Causal Link. J Alzheimers Dis 64(2):363–366. https://doi.org/10.3233/JAD-180266

    Article  PubMed  Google Scholar 

  41. Wu X, Yang H, He S, Xia T, Chen D, Zhou Y, Liu J, Liu M, Sun Z (2022) Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies. Front Immunol 13:872542. https://doi.org/10.3389/fimmu.2022.872542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Juan Gao and Linya Feng contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Juan Gao, Linya Feng, Birong Wu, Weihang Xia, Peng Xie, Shaodi Ma, Haixia Liu & Yehuan Sun

  2. UK Program Site, American University of the Caribbean School of Medicine, Vernon Building Room 64, Sizer St, Preston, PR1 1JQ, UK

    Muzi Meng

  3. Bronxcare Health System, 1650 Grand Concourse, The Bronx, NY, 10457, USA

    Muzi Meng

  4. Chaohu Hospital, Anhui Medical University, No. 64 Chaohubei Road, Hefei, 238000, Anhui, China

    Yehuan Sun

  5. Center for Evidence-Based Practice, Anhui Medical University, Anhui, People’s Republic of China

    Yehuan Sun

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Contributions

Juan Gao: Conceptualization; Writing—original draft; Formal analysis. Linya Feng: Conceptualization; Writing—original draft; Formal analysis. Birong Wu: Writing—review & editing. Weihang Xia: Software; Writing—review & editing. Peng Xie: Software; Writing—review & editing. Shaodi Ma: Methodology; Writing—review & editing. Haixia Liu: Software; Writing—review & editing. Muzi Meng: Writing—review & editing. Yehuan Sun: Conceptualization; Supervision; Formal analysis; Writing—review & editing.

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Correspondence to Yehuan Sun.

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Gao, J., Feng, L., Wu, B. et al. The association between varicella zoster virus and dementia: a systematic review and meta-analysis of observational studies. Neurol Sci 45, 27–36 (2024). https://doi.org/10.1007/s10072-023-07038-7

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