Herpes simplex virus 2 and dementia risk: a systematic review and meta-analysis

Abstract

Introduction – Several potentially modifiable risk factors for dementia have been identified, including infectious diseases. Among the infectious diseases potentially associated with dementia is herpes simplex virus type-2 (HSV-2). Methods – To better characterize the association between HSV-2 and dementia, we conducted a meta-analysis of published peer-reviewed studies reporting HSV-2 exposure and dementia outcomes. Results – Of 626 identified primary studies, eight met our inclusion criteria, with one of these excluded due to overlapping data with another study, yielding seven independent studies (total N = 751, 156). Meta-analyses found no significant association between HSV-2 infection and Alzheimer's disease (pooled odds ratios ≈ 1.1, 95% confidence intervals included the null across all methods). Similarly, when pooling odds ratios across studies examining all-cause dementia, results were non-significant (pooled odds ratios ≈ 1.2, 95% confidence intervals included 1). In contrast, pooled hazard ratios from three studies for all-cause dementia suggested a possible increased risk among individuals with HSV-2 (DerSimonian and Laird pooled hazard ratio = 1.37, 95% CI: 1.00–1.89; Hartung-Knapp-Sidik-Jonkman pooled hazard ratio = 1.35, 95% CI: 0.58–3.14), driven primarily by two significant studies. Discussion – Overall, the available evidence indicates no clear association between HSV-2 and Alzheimer's disease and only one of the two meta-analytic methods shows evidence of a potential relationship with all-cause dementia. These findings support continued investigation into the association between HSV-2 and dementia.