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

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.

Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression

“…There is a growing interest in the role of infectious agents in the pathogenesis of dementia, but evidence is scarce. A recent meta-analysis explored the effect of any of eight human herpesviruses on development of dementia or mild cognitive impairment (MCI) [87]. Recent infection or reactivation of herpes simplex virus type 1 or type 1/2 unspecified, CMV and human herpes virus-6 was associated with dementia or MCI, though results were inconsistent across studies.…”

Association Between Cytomegalovirus End-organ Diseases andModerate-to-Severe Dementia: A Population-Based Cohort Study

“…Because the diagnosis of moderate-to-severe dementia and prescription of anti-dementia drugs were simultaneously regulated by the Korean National Health Insurance Corporation for claiming NHIS insurance benefits, it may have been impossible for false-positive cases indicating spontaneous improvement of moderate-to-severe dementia without medical treatment to occur in this study. The patients at risk for CMV reactivation may also have experienced reactivation of other herpes viruses, particularly HSV-1 and 2, which have been evaluated as one risk factor for AD [12,41]. However, we could not exclude or adjust for HSV infections, because many cases of other viral diseases including HSV could have been underdiagnosed due to self-limited disease course, and consequently would have missed a precise ICD-10 code.…”

Association Between Cytomegalovirus End-organ Diseases and Moderate-to-Severe Dementia: A Population-Based Cohort Study

“…Because the diagnosis of moderate-to-severe dementia and prescription of anti-dementia drugs were simultaneously regulated by the Korean National Health Insurance Corporation for claiming NHIS insurance benefits, it may have been impossible for false-positive cases indicating spontaneous improvement of moderate-to-severe dementia without medical treatment to occur in this study. The patients at risk for CMV reactivation may also have experienced reactivation of other herpes viruses, particularly HSV-1 and 2, which have been evaluated as one risk factor for AD [12,41]. However, we could not exclude or adjust for HSV infections, because many cases of other viral diseases including HSV could have been underdiagnosed due to self-limited disease course, and consequently would have missed a precise ICD-10 code.…”