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Meta-Analysis
. 2019 Mar 18;9(1):4743.
doi: 10.1038/s41598-019-41218-w.

Human herpesvirus infections and dementia or mild cognitive impairment: a systematic review and meta-analysis

Charlotte Warren-Gash  1 , Harriet J Forbes  2 , Elizabeth Williamson  2 , Judith Breuer  3 , Andrew C Hayward  4 , Angelique Mavrodaris  5 , Basil H Ridha  6   7 , Martin N Rossor  6   7 , Sara L Thomas  2 , Liam Smeeth  2
Affiliations
Meta-Analysis

Human herpesvirus infections and dementia or mild cognitive impairment: a systematic review and meta-analysis

Charlotte Warren-Gash et al. Sci Rep. .

Abstract

Interest is growing in the role of infectious agents in the pathogenesis of dementia, but current evidence is limited. We conducted a systematic review and meta-analysis to investigate the effect of any of eight human herpesviruses on development of dementia or mild cognitive impairment (MCI). We searched the Cochrane Library, Embase, Global Health, Medline, PsycINFO, Scopus, Web of Science, clinical trials registers and grey literature sources from inception to December 2017 for observational studies with cohort, case control or self-controlled designs, or randomised controlled trials of interventions against herpesviruses. Pooled effect estimates and 95% confidence intervals (CIs) were generated through random effects meta-analyses across studies with the same design, outcome, and virus type, method and site of measurement. We included 57 studies across various geographic settings. Past infection with herpesviruses, measured by IgG seropositivity, was generally not associated with dementia risk. A single cohort study rated moderate quality showed an association between varicella zoster virus reactivation (ophthalmic zoster) and incident dementia (HR 2.97; 95%CI, 1.89 to 4.66). Recent infection with, or reactivation of, herpes simplex virus type 1 or type 1/2 unspecified, cytomegalovirus and human herpes virus-6 measured by serum IgM, high titre IgG or clinical disease may be associated with dementia or MCI, though results were inconsistent across studies and overall evidence rated very low quality. Longitudinal population studies with robust repeated virus measurements taken sufficiently proximal to dementia onset are needed to establish whether, when and among whom herpesviruses affect dementia risk.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow diagram of study selection.
Figure 2
Figure 2
Effect of herpes simplex virus type 1 infections on dementia risk.!! No adjustment/matching for age. One study assessing the effect of HSV1 in the brain (Lin, 1998) is not included here as it uses the same data as another study (Lin, 2002a); however, it has been retained for sub-group analyses.
Figure 3
Figure 3
Effect of herpes simplex virus type 2 or herpes simplex type unspecified on dementia risk.!! No adjustment/matching for age.
Figure 4
Figure 4
Effect of varicella zoster virus and Epstein-Barr virus on dementia risk.!! No adjustment/matching for age.
Figure 5
Figure 5
Effect of cytomegalovirus on dementia risk.!! No adjustment/matching for age.
See this image and copyright information in PMC

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