Symptomatic Herpes Simplex Virus Infection and Risk of Dementia in US Veterans: a Cohort Study

A Taiwanese cohort study found that symptomatic herpes simplex virus (HSV) infection was associated with a threefold increased risk of developing dementia; however, antiherpetic medication reduced the risk by 90%. Our aim was to verify and further investigate this finding in the US Veteran population using comprehensive electronic medical records from the Veterans Health Administration (VHA). Eighty-seven thousand six hundred eighty-seven Veterans aged 50 or older with symptomatic HSV-1/HSV-2 infection and 217,895 matched controls were identified in VHA data between January 1, 2001, and December 31, 2014, and followed until December 31, 2019. International Classification of Diseases (ICD) codes, ninth and tenth revisions, were used to define dementia. To define HSV infection, we utilized VHA data on antiherpetic medications and laboratory tests in addition to ICD codes. Cox proportional hazards models were used to analyze the effects of HSV infection and antiherpetic medication on the risk of developing dementia. The analysis revealed an adjusted HR of 0.80 (95% CI, 0.78–0.83) for the development of dementia among those with symptomatic HSV relative to those without. Among the 61,776 HSV-1/HSV-2 patients who were treated with antiherpetic medication, 4836 patients (7.8%) developed dementia (adjusted HR = 0.75; 95% CI, 0.72–0.78); this translated to a population average of one additional year of being dementia free in those who were taking antiherpetic medication. In contrast to Tzeng et al. we did not find that HSV infection was associated with an increased risk of dementia. Like their findings, we found that antiherpetic medication was associated with a protective effect against dementia. Future prospective studies are needed to further investigate this effect.