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

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. Data are available upon reasonable request. PharMetrics Plus data may be obtained from IQVIA and are not publicly available. Technical appendix, statistical code are available by contacting the corresponding author.