Increased risk of dementia associated with herpes simplex virus infections: Evidence from a retrospective cohort study using U.S. electronic health records

J Alzheimers Dis. 2025 Mar;104(2):393-402. doi: 10.1177/13872877251317228. Epub 2025 Feb 16.

Abstract

Background: Alzheimer's disease is the most common age-related dementia. Recent compelling evidence from previous retrospective electronic health record (EHRs) studies suggests that herpes simplex virus (HSV) infections may be a risk factor for developing dementia. However, no age and propensity score matched studies have been published in a United States general population cohort study to date.

Objective: We aimed to identify whether HSV infection shows a significantly increased risk of the development of dementia in a sizable and heterogeneous cohort. We investigated whether herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), or coinfections with both serotypes pose a greater risk of developing dementia across different biological sexes and racial groups.

Methods: EHRs from patients with a history of HSV or specific serotypes (HSV1 or HSV2) infection were selected for analysis. These records were compared to a propensity-matched control group and analyzed for hazard and odds ratios through TriNetX.

Results: There was a significant difference in dementia incidence in the HSV-infected group versus the control. Individuals with a history of HSV, HSV1, HSV2, and coinfection all showed a significant risk of developing dementia compared to controls. Males with HSV2 are at a higher risk of dementia outcome than females with HSV2.

Conclusions: While consistent with previous reports, these findings are the first to establish a higher risk of developing dementia in patients who have any HSV diagnosis using a nationwide, population-based matched cohort study in the United States.

Keywords: Alzheimer's disease; clinical outcomes; dementia; electronic health records; herpes simplex virus.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Dementia* / epidemiology
  • Dementia* / virology
  • Electronic Health Records*
  • Female
  • Herpes Simplex* / complications
  • Herpes Simplex* / epidemiology
  • Herpesvirus 2, Human
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology