BMJ Open recently published a large-scale study from the United States that provides compelling evidence supporting a long-suspected link between herpes simplex virus type 1 (HSV-1) and Alzheimer’s disease (AD). The findings not only reinforce the association between viral infections and neurodegeneration but also suggest that antiviral medications may help reduce the risk of developing AD in patients infected with HSV-1.
The study, led by U.S. researchers, utilized real-world data from the IQVIA Parametric Plus claims database, analyzing health records spanning 2006 to 2021. In this robust, matched case–control study, over 344,000 individuals aged 50 and above diagnosed with Alzheimer’s disease were compared with similarly matched individuals without the condition. Matching factors included age, sex, region, year of healthcare entry, and healthcare utilization.
The analysis revealed that HSV-1 infections were nearly twice as common in Alzheimer’s patients compared to controls. Specifically, 0.44% of individuals with AD had documented HSV-1 infections, compared to 0.24% in the non-AD group. Statistically, those with HSV-1 had an 80% increased likelihood of developing Alzheimer’s (adjusted odds ratio: 1.80; 95% CI: 1.65–1.96).
The study also explored the potential protective effect of antiviral therapy. Patients with HSV-1 who were treated with antiherpetic drugs, such as acyclovir, showed a 17% lower risk of progressing to Alzheimer’s than those who did not receive antiviral treatment (adjusted hazard ratio: 0.83; 95% CI: 0.74–0.92). These medications function by targeting the viral enzyme thymidine kinase, which activates drugs like acyclovir into their triphosphate form, subsequently disrupting viral DNA replication.
HSV-1 infection has been shown in lab settings to induce hallmark Alzheimer’s pathologies, including amyloid-beta plaque formation and tau protein hyperphosphorylation. The current epidemiological evidence aligns with these mechanistic insights, strengthening the hypothesis that viral pathogens may play a causal role in neurodegenerative disease development.
This study adds substantial weight to the growing body of literature connecting viral infections with Alzheimer’s. It opens the door to potentially repurposing widely available antiviral drugs as part of preventive strategies against dementia.
While further research is needed to fully understand the biological pathways involved, this study highlights an urgent need to explore infectious contributors to neurodegeneration. It also presents a promising avenue for future clinical trials focused on early intervention in high-risk groups.
As Alzheimer’s disease continues to pose an immense global health challenge, targeting treatable viral infections like HSV-1 may offer a novel and cost-effective approach to delay or prevent the onset of dementia.
Reference
- Liu Y, Johnston C, Jarousse N, et alAssociation 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.
- Poole CL, James SH. Antiviral Therapies for Herpesviruses: Current Agents and New Directions. Clin Ther. 2018 Aug;40(8):1282-1298.
- Linard, M., Garrigue, I., Vellas, B. et al. Association between herpes simplex virus infection and Alzheimer’s disease biomarkers: analysis within the MAPT trial. Sci Rep 15, 2362 (2025). https://doi.org/10.1038/s41598-024-84583-x