Association between herpes simplex virus 1 and dementia: a systematic review protocol

Abstract

Introduction: Herpes simplex virus 1 (HSV-1) infects approximately two-thirds of the global population under the age of 50 years. Although widely prevalent, the possible implications of HSV-1 in neurodegenerative diseases, especially dementia and Alzheimer's disease, remain poorly understood. This review seeks to elucidate this association and explore the potential benefits of preventing or treating herpesvirus infections on dementia risk. The goal is to enhance our understanding of HSV-1's potential role in dementia, which could inform the development of future therapeutic interventions for these conditions.

Methods and analysis: PubMed, Embase (Elsevier/Ovid), Web of Science, Scopus, Global Health, PsycInfo, Cochrane Library and Clinicaltrials.gov will be searched from the inception of each respective database. Studies that have HSV-1 as an exposure and dementia, or its subtypes, as a primary outcome will be included. Two researchers will independently screen titles, abstracts and full texts, with discrepancies resolved by a third researcher. Systematic data extraction from eligible studies will be performed using a standardised template. Risk of bias of individual studies will be assessed with the Cochrane Collaboration approach. We will assess the overall quality of cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Statistical analysis will employ a random effects model, and heterogeneity will be determined with Cochrane's Q test and assessed using I². Studies will be grouped by population subgroups and dementia subtypes when possible to explore nuances in results. We will consider performing meta-regression if heterogeneity remains after subgroup analyses. All statistical analyses will be conducted using Stata V.18 software (College Station, Texas, USA).

Ethics and dissemination: No ethical approval is required since data will be collected from existing studies. The review will be disseminated through peer-reviewed publication and at national and international conferences.

Prospero registration number: CRD42024516789.

Keywords: Dementia; EPIDEMIOLOGIC STUDIES; Epidemiology; Infectious disease/HIV; Public health.