Alzheimer’s disease (AD) has been linked to herpesviruses, and evidence suggests that patients receiving antiherpetic treatments show a lower risk of developing AD. Globally, approximately 35.6 million individuals are affected by dementia, with 7.7 million new cases diagnosed annually. AD is a degenerative, chronic, and slowly progressing illness that causes 60% to 80% of dementia cases, resulting in long-term medical costs.
A significant financial burden resulted from the increase in the incidence rate in 2020; the overall cost of healthcare for treating AD reached approximately $305 billion. The connection between exogenous infections and AD gained attention after the discovery of the antimicrobial properties of the amyloid-beta (Aβ) peptide. Notably, more than two-thirds of individuals worldwide aged 0 to 49 years were infected with the common neurotropic virus, herpes simplex virus type 1 (HSV-1), in 2016.
Neurotropic Herpesviridae members infect primary human spinal astrocytes, leading to the production of intracellular amylin and Aβ. Taiwanese national health database revealed that people with HSV-1 who were treated with antiherpetic medications had a decreased risk of dementia compared to those who were diagnosed with the same but were not treated.
IQVIA PharMetrics Plus database is one of the largest commercial claims databases in the United States. This database includes prescription data, outpatient medications, prices, and detailed enrollment information, offering a longitudinal view of healthcare services. All data are deidentified and randomized at the patient level to ensure compliance with the Health Insurance Portability and Accountability Act (HIPAA). The IQVIA PharMetrics Plus claims database was used to identify AD patients aged ≥50 years who were diagnosed between 2006 and 2021 for a matched case-control study.
Subjects with AD and matched controls were selected in a 1:1 ratio based on factors such as sex, age, geographic area, database entry year, and total number of medical visits. International Classification of Diseases (ICD) codes were used to record diagnoses of HSV-1 and other herpesviruses (HSV-2, VZV, and cytomegalovirus [CMV]) made before the index date. Antiherpetic medication use, administered after HSV diagnosis but before AD or AD-related dementia (ADRD) onset, was identified using National Drug Code (NDC) records.
The multivariate cox proportional hazards (PH) model was used to evaluate the association between the antiherpetic medication use and the risk of AD and ADRD in individuals with a history of HSV-1. The odds ratio (OR) and 95% confidence interval (CI) for HSV-1 diagnoses were calculated by conditional logistic regression. The model did not incorporate age and sex variables, as the cases and controls had already been matched based on these criteria.
A total of 344,628 AD case-control pairs were included in the research. When compared to 823 control subjects, 1507 AD patients had a history of HSV-1 diagnosis. The results indicated that antiviral use was associated with a lower risk of AD development in HSV-1 patients compared to those who did not receive antiviral treatment. HSV-1 may increase susceptibility in ApoE ε4 carriers and cause AD through amyloid-β reactions and brain inflammation.
These findings of the study are consistent with those of previous studies; however, some differences exist due to variations in study design and databases. Observational studies continue to suggest an association between symptomatic HSV-1 infection and AD risk. However, further research is necessary to determine whether inhibition of neurotropic viruses can alter the progression of AD and ADRD.
Reference: Liu Y, Johnston C, Jarousse N, et al. Association between herpes simplex virus type 1 and the risk of Alzheimer’s disease: a retrospective case–control study. BMJ Open. 2025;15:e093946. doi:10.1136/bmjopen-2024-093946
