Cold Sore Virus Linked to Higher Alzheimer’s Risk
A study finds that HSV-1 infection may raise Alzheimer's risk, with antiviral treatment showing a protective effect.
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Could a common virus be a hidden risk factor for Alzheimer’s?
A US study suggests that symptomatic infection with herpes simplex virus type 1 (HSV-1), the virus that causes cold sores, may increase the risk of Alzheimer’s disease. People treated with antiviral drugs had a lower risk, hinting at a possible protective effect.
The study was published in BMJ Open.
How the cold sore virus became a suspect in Alzheimer’s disease
Alzheimer’s disease affects ~35.6 million people globally, with 7.7 million new cases each year. It makes up 60–70% of all dementia cases and cost the U.S. over $300 billion in 2020. But despite its impact, we still don’t fully understand what causes it.
One idea that’s been gaining attention is that infections might play a role. The cold sore virus has been a suspect for decades. It infects ~66% of people under 50 and stays in the body for life. In some people, it reactivates and causes cold sores, although in others it may do more.
In the 1990s, Prof. Ruth Itzhaki was one of the first to show the presence of HSV-1 DNA in the brain plaques that are typical in Alzheimer’s. Her lab also found that the virus can trigger Alzheimer’s-like damage in neurons, especially in people with a genetic risk factor called APOE ε4.
Now, 30 years later, recent lab studies are supporting her findings. HSV-1 has been shown to cause amyloid-beta (Aβ) buildup, which forms plaques in the brain.
“It has been reported that Aβ peptides are deposited in response to HSV infection and protect host cells by blocking viral fusion with the plasma membrane,” the authors of the new study explain. “Consistently, Aβ exhibits antimicrobial properties against various pathogens, including HSV-1.”
Still, large-scale, real-world data has been missing. The new study looks at insurance records for signs that HSV-1 might raise the risk of Alzheimer’s, and whether antiviral drugs can reduce it.
Link identified between HSV-1 and Alzheimer’s
The study looked at U.S. insurance records from 2006 to 2021. The team compared 2 matched groups: 344,628 people with Alzheimer’s disease and an equal number without any diagnosed neurological conditions. They matched each pair by age, sex, location, healthcare usage and when they entered the database.
Everyone in the study was at least 50 years old with the average age at 73 years. Most were older adults, and two-thirds of the Alzheimer’s group were women.
Only 0.24% of the control group had a record of HSV-1, compared to 0.44% of the Alzheimer’s group, translating to an 80% higher chance of Alzheimer’s in people with HSV-1, after adjusting for other factors.
The link between HSV-1 and Alzheimer’s was strongest in people aged 75 and over, where the odds of developing Alzheimer’s were more than twice as high.
The researchers then looked at the effect of antiviral treatment. Of the 2,330 people with HSV-1, ~40% had taken antiherpetic drugs. These treated patients were 17% less likely to develop Alzheimer’s than those who hadn’t been treated.
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Similar associations were found for HSV-2 and varicella zoster virus, both of which were more common in people with Alzheimer’s than in the control group.
Herpes virus treatment and Alzheimer’s prevention
While the study cannot establish causation, it shows that people with symptomatic HSV-1 had significantly higher odds of developing Alzheimer’s. Those who received antiviral treatment had a modest but measurable reduction in risk, suggesting that suppressing the virus could have a protective effect.
HSV-1 is common, and many people never show symptoms. If the virus does contribute to Alzheimer’s in some people, managing it early, especially in those at higher genetic risk, might help delay or prevent the disease.
“These findings place an even greater emphasis on viewing the prevention of herpes viruses as a public health priority,” the authors added.
Lab studies are still needed to explain how HSV-1 might damage the brain. Clinical trials could show whether antiviral drugs change Alzheimer’s risk, and larger studies across different health systems would help confirm these patterns.
“While the molecular mechanisms remain to be fully elucidated, these results are indicative of a possible role for antiherpetic therapy in mitigating dementia risk,” the authors concluded.
Reference: Liu Y, Johnston C, Jarousse N, Fletcher SP, Iqbal S. 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
This article is a rework of a press release issued by BMJ Open. Material has been edited for length and content.
