Association between herpes simplex virus type 1 and the risk of Alzheimer's disease: a retrospective case-control study

BMJ Open. 2025 May 20;15(5):e093946. doi: 10.1136/bmjopen-2024-093946.

Abstract

Objective: A growing body of evidence points to a role for herpesviruses in the development of Alzheimer's disease (AD) and a reduced risk of AD among patients receiving antiherpetic medications. We investigated the association between herpes simplex virus type 1 (HSV-1) and AD using real-world data (RWD) from USA.

Design: In a matched case-control study, patients with AD aged ≥50 years diagnosed between 2006 and 2021 were identified from the IQVIA PharMetrics Plus claims database. Controls were matched in a 1:1 ratio with subjects with AD on age, sex, region, database entry year and healthcare visit numbers.

Results: The study included 344 628 AD case-control pairs. History of HSV-1 diagnosis was present in 1507 (0.44%) patients with AD compared with 823 (0.24%) controls. HSV-1 diagnosis was found to be associated with AD (adjusted OR 1.80; 95% CI 1.65 to 1.96). Patients with HSV-1 who used antiherpetics were less likely to develop AD compared with those who did not use antiherpetics (adjusted HR 0.83, 95% CI 0.74 to 0.92).

Conclusions: Findings from this large RWD study implicate HSV-1 in the development of AD and highlight antiherpetic therapies as potentially protective for AD and related dementia.

Keywords: Case-Control Studies; Dementia; VIROLOGY.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / virology
  • Antiviral Agents / therapeutic use
  • Case-Control Studies
  • Female
  • Herpes Simplex* / complications
  • Herpes Simplex* / drug therapy
  • Herpes Simplex* / epidemiology
  • Herpesvirus 1, Human*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology

Substances

  • Antiviral Agents