May 20, 2025

expert reaction to study of the cold sore virus herpes simplex 1 and risk of Alzheimer’s

A study published in BMJ Open looks at the association between herpes simplex virus type 1 and the risk of Alzheimer’s disease. 

Dr Sheona Scales, Director of Research at Alzheimer’s Research UK:

“There’s an increasing amount of evidence that suggests our body’s response to certain viruses could put us at an increased risk of developing Alzheimer’s disease in later life. 

“These recent findings from a large study using US health records propose that infection with HSV-1 – a common virus that causes cold sores – may be associated with an increased risk of Alzheimer’s disease. The researchers also state that taking medicines to treat HSV-1 infections could reduce the risk, but this is still very early work and needs more investigation.  

“Despite the large sample size, this research has limitations partly due to only using health records and administrative claims data. 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. Although cases were matched with controls, diagnosing Alzheimer’s disease, especially in the early stages, remains a challenge.    

“The study authors found that some people receiving medicines to treat HSV-1 infections had a lower risk of Alzheimer’s disease, however a lot more work is needed to unpick this.  

“We know there are 14 established risk factors for dementia, and there’s not enough evidence to include infections in this list.  This study doesn’t tell us if infections are causing the risk, it only shows an association. Further research is needed to understand what the underlying biology around this is.”

Prof Cornelia van Duijn, Research Director of Brain Health at HDR UK and Professor of Epidemiology at the Nuffield Department of Population Health at University of Oxford, said:

“Again a carefully conducted study adding to the growing evidence that various common viruses may determine the risk of Alzheimer’s disease, in particular in the elderly (70+ years).

“Matching Alzheimer’s patients carefully with controls in the IQVIA PharMetrics Plus claims database, the study further shows that treating those with an active herpes simplex 1 (HSV-1) infection with antiherpetic medication reduces the risk and postpones the onset of Alzheimer’s disease.

“Smaller but significant effects are also seen for HSV-2 and varicella zoster virus (VZV). 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.”

Dr David Vickers, Cumming School of Medicine, University of Calgary, Canada, said:

“Declining HSV-1 rates in the U.S. since the late-70’s challenge the authors’ claim that Alzheimer’s disease (AD) will surge without intervention. This pharma-funded research exaggerates the role of HSV-1, failing to appreciate its absence in 99.56% of AD cases. The observed 17% hazard reduction with antiherpetic drugs translates to a mere nine-month delay in AD onset, offering no meaningful relief to the US$305 billion costs for treatment.

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

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said:

“This study reports that diagnosis of herpes simplex virus type 1 (HSV-1) infection is associated with increased risk of diagnosis of Alzheimer’s disease-related dementia. Scientists examined data from almost 700,000 people in a medical insurance claims database and found that in addition to an increased proportion of people with Alzheimer’s disease having a diagnosis of HSV-1, people with HSV-1 who were treated for the viral infection with “antiherpetic” medication were less likely to develop Alzheimer’s than those who did not have treatment. 

“This is a well-conducted study adding to strong data in the field linking HSV-1 and other viral infections to increased risk of developing Alzheimer’s disease, but 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. 

“Why viral infections may increase risk of dementia is not fully understood, but the most likely explanation is that infections increase inflammation in the body and contribute to age-related brain inflammation.  More research is needed to understand the best way to protect our brains from Alzheimer’s disease as we age, including a better understanding of links between viral infection and Alzheimer’s risk.”

Dr Richard Oakley, Director of Research and Innovation at Alzheimer’s Society, said:

“This study adds to the growing interest in a possible link between the virus that causes cold sores and Alzheimer’s disease. Results from this observational study suggested that people with recorded cold sore infections were more likely to develop Alzheimer’s disease, and interestingly those prescribed antiviral drugs had a slightly lower risk. 

“But this doesn’t prove that cold sores cause Alzheimer’s disease, or that antivirals prevent it. The data came from insurance records, often based on self-reported symptoms which may miss or misclassify infections, and didn’t track how often people had cold sores or how consistently they took medication. 

“Much more research is needed to explore exactly how viruses might be involved and before we can draw firm conclusions. It is critical we explore every avenue to understand the complex causes of the diseases which cause dementia – infections are a growing area of interest.  

“If you are worried about a cold sore or your general health, be sure to seek the appropriate help from a health professional.” 

From the Spanish SMC:

Prof Alberto Ascherio, Professor of Epidemiology and Nutrition at the Harvard T.H. Chan School of Public Health (United States) and Professor of Medicine at Harvard Medical School, said:

“This is a high-quality study that stands out mainly for its sample size. The results confirm previous findings that people with a history of cold sores have a higher risk of developing Alzheimer’s disease and that this risk appears to be reduced in people who receive antiviral treatment.

“This is an observational study based on electronic data of varying quality, so the conclusions cannot be considered definitive. For example, the vast majority of cold sore episodes are not reported in medical records, so the study’s conclusions apply to a highly selected subgroup of individuals with clinical episodes of cold sores, perhaps due to clinical severity or the presence of other factors. For this reason, it would be premature for people with cold sores to worry about having an increased risk of Alzheimer’s disease. However, there is growing evidence that viral infections may affect the risk of Alzheimer’s disease, and it is important to initiate more definitive research.”

From the Australian SMC:

Prof Ashley Bush, Clinical Lead Mental Health Mission at The Florey, Australia, said:

“This is an important, large, case-control epidemiology study that shows that people suffering with Alzheimer’s disease or with other Alzheimer-like dementia (e.g. fronto-temporal dementia) are substantially (about 80%) more likely to have been infected with the viruses that cause cold sores, genital herpes, chicken pox or shingles. Further, people who were taking antivirals for cold sores were 17% less likely to develop Alzheimer’s disease over a 15 year period.

“These findings come in the wake of another recent report¹ that showed that shingles vaccination decreased the probability of a new dementia diagnosis during the follow-up period of 7 years by 2%. Some scientists like Prof Ruth Itzhaki in Manchester and the late Rob Moir at Harvard have proposed that dementias like Alzheimer’s are provoked by viral infection. Herpes virus lives dormant in nerve cells, and it is thought that the pathology of the dementia is brought about by a defence to these infection gone wrong.

“It is unlikely that viral infection can explain all causes of dementia, but these recent papers implicate the infections are playing a role in accelerating these diseases. It certainly encourages more research in this direction and as to whether lifelong antivirals should be considered as preventive therapy for people who have had one of these infections.”

¹ (Pomirchy M, Bommer C, Pradella F, Michalik F, Peters R, Geldsetzer P. Herpes Zoster Vaccination and Dementia Occurrence. JAMA. 2025 Apr 23; Epub 2025 Apr 23)

Prof Brenda Gannon, Professor of the Health Economics of Ageing at the University of Queensland, said:

“This research provides further evidence for the link between the common cold sores from HSV1 and Alzheimer’s Disease. The study now proposes that people with HSV who are treated with anti-viral medicine are less likely to develop AD. Using large scale administrative data from the US, the findings are suggestive of a protective effect of anti-viral treatment. This could be beneficial for Australians who suffer from the common cold sores and who would benefit from anti-viral treatment for their cold sores. It does not mean it could reduce the probability of AD.

“Further research would be required to ensure the study is more widely representative, since the authors note that not all populations are included in the data, e.g. those over 65 who receive free health care (Medicare). The study does not provide detail on who may benefit, for example does it help disadvantaged groups more, and who does it work together with other non-pharmacological treatments for lifestyle improvement.

“Overall, the study indicates some potential, but much more research would be required to determine if the anti-viral therapies for people with cold cores, is in fact going to reduce their probability of getting Alzheimer’s disease.

“As the authors state, it does not indicate cause and effect, but they do find it a potential avenue to explore further.

“The study did not include public involvement – but inclusion of the public, even on an advisory capacity would be useful, to help design the research questions and relevant factors included in the study.

“From a health economics perspective, it is unlikely that anti-viral therapy would be funded for the Australian population, until further evidence on effectiveness in prevention and then cost-effectiveness overall, including additional use of health care resources, is provided. More details on the health and socio-economics status of individuals are also warranted, to help determine who may benefit from the therapy.”

‘Association between herpes simplex virus type 1 and the risk of Alzheimer’s disease: a retrospective case control study’ by Yunhao Liu et al. was published in BMJ Open at 23.30 on Tuesday 20 May.

DOI: 10.1136/bmjopen-2024-093946

Declared interests

Cornelia van Duijn: “I receive funding from GSK (related to VZV vaccination) and NovoNordisk (unrelated to virus treatment/prevention), and have received funding from JNJ/Jansen Pharmaceutics (unrelated to virus treatment/prevention).”

David Vickers: “I have no interests or conflicts, financial or otherwise, to declare.”

Tara Spires-Jones: “I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.”

Ashley Bush: “I have no relevant conflicts.”

Brenda Gannon: “No COI”

For all other experts, no reply to our request for DOIs was received.