Are Cold Sores Really Linked To Alzheimer’s Disease? Here’s What The Experts Are Saying

What was the study about and what did it show?

The newly published paper comes from an international team of researchers working at Gilead Sciences Inc., a US pharmaceutical company developing drugs for a number of different diseases, including HSV-1.

The study had a retrospective case-control design. Patients with a diagnosis of Alzheimer’s disease or Alzheimer’s disease-related dementia (ADRD) were matched with a control participant of the same age and sex, living in the same region, and with a similar health history except for one key difference: the controls had no history of neurological disorders. In total, 344,628 pairs were included.

Of the people with Alzheimer’s or ADRD, it was found that 0.44 percent of them had been diagnosed with HSV-1. In the control group, it was 0.25 percent. These are both tiny fractions of the overall number of people, but the difference between these two figures was found to be significant.

After adjusting for other health conditions that could play a role, the team concluded that those with Alzheimer’s disease/ADRD were 80 percent more likely to have been diagnosed with HSV-1.

Another finding was that those who had used an antiviral medication to treat their HSV-1 seemed to be somewhat protected and were 17 percent less likely to develop Alzheimer’s.

While the topline findings focused on HSV-1, the team also looked at two similar viruses: HSV-2, the more common cause of genital herpes; and varicella zoster virus (VZV), the virus responsible for chickenpox and shingles. Both of these were also associated with an increased risk of Alzheimer’s disease.

What can be concluded from this study?

This kind of study can only show that two factors are linked in some way; it cannot show that one causes the other. There are also limitations to the study – as with every research project – that must be accounted for.

“Despite the large sample size, this research has limitations partly due to only using health records and administrative claims data,” said Dr Sheona Scales, Director of Research at Alzheimer’s Research UK, in a statement to the Science Media Centre. “Most people infected with HSV-1 don’t have any symptoms so some infections might not have been recorded. Infections predating the information recorded are also not available.”

Other scientists have been more critical. Dr David Vickers, of the Cumming School of Medicine at the University of Calgary, commented, “This pharma-funded research exaggerates the role of HSV-1, failing to appreciate its absence in 99.56 percent of [Alzheimer’s disease] cases.”

“The study’s data source makes its findings ungeneralisable, and it overstates a minor infection as a ‘public health priority’ to justify unnecessary treatment.”

However, a number of others, including Professor Tara Spires-Jones of the University of Edinburgh and Professor Cornelia van Duijn of the University of Oxford, praised the study for its careful methodological design, whilst acknowledging that this can’t be the end of the story.

“More research is needed to understand the best way to protect our brains from Alzheimer’s disease as we age,” said Spires-Jones, adding that “it is important to note that HSV-1 infection, which is extremely common in the population, is by no means a guarantee that someone will develop Alzheimer’s.”

HSV-1 and Alzheimer’s: What evidence do we already have?

The study is part of a much broader conversation and a growing body of evidence suggesting that HSV-1 and similar viruses can have a direct impact on the brain, which may include Alzheimer’s and other forms of dementia.

A 2024 paper in the Journal of Virology used a mouse model to show that HSV-1 can enter the brain via both the brainstem and olfactory nerve, triggering an inflammatory response that can persist when the virus is no longer detectable.

Earlier this year, a team at the University of Illinois Chicago led a study that found HSV-1 particles can be shed in tears and can reach the nasal cavity that way, moving directly into the brain and potentially contributing to neurodegeneration.

A 2021 paper in the journal Vaccines even went as far as to argue that the evidence for a “major role” for HSV-1 in Alzheimer’s disease was “overwhelming”.

“We’re not saying viruses explain everything. But they may be central to it. This is no longer a fringe theory – it’s the next phase of Alzheimer’s research, and we’re pursuing it,” said Dr Bryce Vissel, Director of the Centre for Neuroscience and Regenerative Medicine at St Vincent’s Hospital Sydney, in a comment to the Australian Science Media Centre. Vissel’s research group are also actively conducting studies in this area.

Even though most of the experts agree that more research is needed to better understand what’s going on, some have pointed to the fact that this study seems to suggest that treating HSV-1 with antiviral medications could help combat the potential damage to the brain. They say doing more to treat and detect these infections, even while the research continues, may not be a bad thing.

“With many GPs and the population being unaware of the dementia related benefits of treating HSV infections and preventing VZV activation through vaccination, it is time to call for actions informing those working in primary care as well as the population at large,” said van Duijn.

Unless you were vaccinated, chances are you were exposed to VZV as a kid; there are now vaccines available that prevent the virus reactivating later in life as shingles, and you can ask a healthcare professional about availability where you are. As for HSV-1 and 2, many people may be infected without ever having any symptoms.

“If you are worried about a cold sore or your general health, be sure to seek the appropriate help from a health professional,” recommends Dr Richard Oakley, Director of Research and Innovation at Alzheimer’s Society.

The new study is published in the journal BMJ Open.