This research provides further evidence for the link between the common cold sores from HSV-1 and Alzheimer’s Disease. The study now proposes that people with HSV who are treated with anti-viral medicine are less likely to develop Alzheimer’s Disease. 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 Alzheimer’s Disease.

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 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.

A newly published study suggests that a virus many of us carry for life — the same one that causes cold sores — may increase the risk of developing Alzheimer’s disease. 

And crucially, people treated with antivirals may be partly protected.

Our research team at St Vincent’s has been asking: what if common viruses are helping cause Alzheimer’s — and we already have ways to fight back?

A number of recent studies are now adding weight to that idea. Research from Oxford and Stanford has shown that shingles vaccination — which targets varicella zoster virus (VZV), another herpesvirus — is associated with a 20% reduction in dementia risk. The latest study, published in BMJ Open by Liu and colleagues, analysed health records from over 300,000 people and found that those with a diagnosis of herpes simplex virus type 1 (HSV-1) had a significantly higher risk of developing Alzheimer’s. Those who received antiviral treatment were associated with a 17% lower risk.

These viruses are incredibly common. Most people are infected in childhood. They retreat into the nervous system and stay there for life. Under certain conditions — stress, inflammation, immune decline — they can reactivate. This may trigger an inflammatory cascade in the brain that leads to the synapse loss and memory decline characteristic of Alzheimer’s.

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.

The BMJ Open study is a case–control analysis using US health insurance data between 2006 and 2021. It matched over 340,000 people with and without Alzheimer’s and assessed their history of herpesvirus infections. HSV-1 diagnosis was associated with an 80% increased risk of Alzheimer’s. Antiviral use — including acyclovir or valacyclovir — was linked to reduced risk, particularly in older adults. While the data are observational, the signal is strong and consistent with a growing body of international evidence.

This aligns with the broader shift we’ve long argued is needed in the field. For decades, Alzheimer’s research focused almost exclusively on amyloid — the protein that builds up in affected brains. But despite billions in investment, anti-amyloid drugs have consistently failed to prevent or reverse the disease. An increasingly supported view — and one we’ve championed — is that amyloid might not be the cause, but a response: part of the brain’s defence against microbial threats. If that’s true, clearing it without addressing the trigger may be ineffective.

In 2014, our team argued in a peer-reviewed article that viruses and immune dysfunction were credible contributors to Alzheimer’s disease (Vissel et al., Acta Neuropathologica Communications). We called for a broader research agenda that included microbial and immune pathways. That position remains just as urgent — and is now being reinforced by new clinical data. (See also SMH article, 2018).

Since then, our team has studied immune responses in Alzheimer’s-affected brain regions, developed experimental models to investigate immune signalling, and is now exploring how viral activity may contribute to synapse loss. We are preparing a clinical study focused on early-stage memory loss — to directly assess viral reactivation and immune involvement. Together with international collaborators, we’re building tools to detect these changes in real time and test how they might be stopped.

Alzheimer’s is the leading cause of death for Australian women, and second overall. It affects over 500,000 Australians and costs the economy more than $15 billion a year.

If herpesviruses play even a part in causing Alzheimer’s — and if we can intercept that process — then we’re not just talking about understanding the disease. We’re talking about preventing it. That changes everything.

A study published in BMJ provides new evidence that targeting specific viruses (in this case the Herpes virus that causes cold sores) may reduce dementia risk. This may contribute to the development of novel interventions for dementia prevention and treatment. It follows a recent study in Nature showing that vaccination against a related Herpes virus (the one causing shingles) could delay onset of dementia. This industry-funded new study is observational, therefore does not prove 'cause and effect’.

Nevertheless, it builds on other studies linking these kinds of viral infection to the risk of Alzheimer’s disease, the most common form of dementia. Just like the previous study using a vaccine, the antiviral drug used in this new study is expected to reduce the viral load in the nervous system (and elsewhere) and therefore together these studies suggest that targeting such viruses may have potential as approaches to delay onset, and/or slow progression, of Alzheimer’s disease (and perhaps other forms of dementia).

It is important now to follow this up with studies to address causation, and mechanisms involved. Working out how such an antiviral drug (against a specific Herpes virus) might be protective against dementia could lead to the development of novel approaches to delay onset of Alzheimer’s disease.  This study could also lead to future antiviral interventions whose primary aim is to prevent dementia.

This is an important study that adds to the existing evidence that herpes simplex and herpes zoster infection are risk factors and possibly exacerbating factors for Alzheimer’s, but unlikely the cause. The data show a modest association between a diagnosis of herpes simplex as well as herpes zoster and Alzheimer’s especially in the elderly. Further, there was a modest protective effect of antiherpes medication.

Despite the very large numbers of patients derived from an electronic database, the study is limited by its retrospective nature, the absence of a proven mechanism, the inability to validate Alzheimer's disease diagnosis, and the inability to determine details regarding antiherpes medication such as dose and duration. However, such limitations are inherent in any such retrospective database-driven study.

Nonetheless, the results further confirm an association between herpes simplex as well as herpes zoster and Alzheimer’s. Further research will need to define the precise nature of the relationship.

The study is interesting and there is growing interest in the role of viruses and infections as increasing risk of Alzheimer’s Disease. 

There are a number of confounders that were not considered in the analysis which weaken the robustness of the results, eg the case control study did not account for differences in the overall dementia risk factor profiles between groups. There needs to be consideration of the type of HSV1 infection that would be recorded in medical records, as presumably these would be much more severe than regular infections. Severity of infection was not considered in the analysis.

Factors associated with obtaining medication may also be confounders, such as more severe infection, better access to healthcare, and higher income. Hence, the findings require further replication using better-designed studies that properly take account of these factors to better eliminate bias.

This is an important, large case-control epidemiology study that shows that people suffering from Alzheimer’s disease or 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 report (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) 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 Professor 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 infections gone wrong. It is unlikely that viral infection can explain all causes of dementia, but these recent papers suggest that 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.