Herpes Simplex Virus Infection and Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies (cohort and case-control)
PubMed 40934136 · doi:10.1159/000548365
What was done
A systematic review and meta-analysis of observational studies searched PubMed, Embase, Web of Science, and Cochrane Library through July 31, 2024. The authors evaluated the relationship between herpes simplex virus (HSV) infection and Alzheimer's disease (AD) risk using a generic inverse variance random-effects model to pool odds ratios (ORs) and hazard ratios (HRs).
What was found
The meta-analysis included 26 studies with 1,213,193 total participants. HSV infection was associated with increased odds of AD in case-control studies (OR = 1.32, 95% CI: 1.12 to 1.55; I2 = 22.7%) and an elevated risk in cohort studies (HR = 1.20, 95% CI: 1.10 to 1.31; I2 = 11.0%). HSV-1 infection specifically was associated with higher odds of AD (OR = 1.46, 95% CI: 1.14 to 1.86; I2 = 3.1%).
Why it matters
This review pools large-scale observational evidence indicating that HSV, particularly HSV-1, is associated with a modest increase in AD risk. The authors emphasize these findings are hypothesis-generating rather than definitive proof of causality.
Limits
The underlying evidence consists entirely of observational studies (case-control and cohort), which cannot establish causality. The abstract does not detail how HSV infection or AD were diagnosed across primary studies, nor whether critical confounders such as APOE genotype or antiviral treatments were consistently adjusted for.
Cited by
- supports Herpesvirus infection is associated with an increased risk of developing Alzheimer's disease.
- partial Herpes simplex virus type 1 (HSV-1) cold sores are associated with an increased risk of developing Alzheimer's disease.