There are more and more studies linking certain neurodegenerative diseases, such as Alzheimer’s and amyotrophic lateral sclerosis (ALS) with some viruses. The latest is a study published in “Neuron” that claims to have found significant associations between viruses and these pathologies that represent a serious public health problem.
The work of the US National Institutes of Health (NIH) analyzed the medical records of hundreds of thousands of people in Finland and the United Kingdom to assess the possibilities that some viral infections, such as the flu, could lead to a diagnosis of neurodegenerative disorder.
The scientists found that there could be at least 22 pairings between a diagnosis of a neurodegenerative disorder and a previous viral infection that necessitated a hospital visit. And the strongest risk association was between viral encephalitis, an inflammation of the brain caused by a virus, and Alzheimer’s disease.
On the other hand, infections caused by the influenza virus that require hospitalization because they cause pneumonia have also been related to the diagnosis of some diseases, such as dementia, Parkinson’s disease and ALS.
The study results also suggest the possibility that existing vaccines may help some people reduce their risk of experiencing these disorders.
“Neurodegenerative disorders are a group of diseases for which there are very few effective treatments and many risk factors,” he says. Andrew B. Singletondirector of the NIH Center for Alzheimer’s-Related Dementias and an author of the study.
“Our results support the idea that viral infections and related inflammation in the nervous system may be common, and possibly preventable, risk factors for these types of disorders.”
People with viral encephalitis were at least 20 times more likely to be diagnosed with Alzheimer’s than those without the virus.
Neurodegenerative disorders damage different parts of the nervous system. These usually happen late in life and cause a variety of problems, including thinking, remembering, and moving.
This is not the first study to establish this association. Several previous investigations have suggested that certain viruses may play a role in each of these disorders..
For example, a 1991 study of autopsy brain tissue suggested that there may be a link between the herpes simplex virus and Alzheimer’s disease. More recently, scientists found evidence of a link between the Epstein Barr virus and multiple sclerosis by analyzing blood samples and medical records from patients.
different approach
Following these investigations, which had searched for shape links between a single neurodegenerative disorder and a specific virus, the NIH team decided to try a different, more data-driven approach. «By using medical records, we were able to systematically search for all possible links in one go», explains Michael Nalls, lead author of the study.
The researchers pulled the medical records of 300,000 people stored in FinnGen. Specifically, they looked for people who had a diagnosis of one of six neurodegenerative disorders: Alzheimer’s, ALS, dementia, multiple sclerosis, Parkinson’s, or vascular dementia.
They later verified whether a viral infection had caused any of these people to have been hospitalized before. Hospitalizations due to Covid-19 were excluded.
In FinnGen, a large Finnish biobank that includes digital healthcare data, the researchers found nearly 26,000 people who had one of the brain diseases. They then checked to see if the same people had also had one of a panoply of viral infections. In 45 cases, they found a “pairing“Significant risk of infection and brain disease, meaning that people with the brain disease were more likely to have had that infection than the nearly 309,000 controls without brain disease.
They then searched for the same 45 couples in another large database, the UK Biobank, where they analyzed data from 106,000 people, including more than 96,000 controls. They were only able to replicate 22 of the associations. They were the ones they focused on in the study.
Of all neurodegenerative disorders, dementia had the most associations, with links to six different virus exposures: viral encephalitis, viral warts, other viral illnesses, flu viruses, and pneumonia.
People with viral encephalitis were at least 20 times more likely to be diagnosed with Alzheimer’s than those without the virus.
And severe cases of flu and pneumonia were linked to the widest range of risks for neurodegenerative disorders, except for multiple sclerosis.
Nalls qualifies that we are not talking about a «common coldbut of infections that required medical attention.
The good news, he acknowledges, is that the fact that vaccines reduce the risk or severity of many of the viral illnesses seen in this study “raises the possibility that the risks of neurodegenerative disorders might also be mitigated.”
The risks associated with some viruses may disappear over time.
Additionally, further analysis of the FinnGen data suggested that the risks associated with some viruses may disappear over time.
Finally, it is known that about 80% of the viruses observed in this study can invade the nervous system and trigger the inflammatory response of the immune system.
“The results of this study provide researchers with several critical new pieces of the puzzle of neurodegenerative disorders,” Nalls acknowledges. Moving forward, we plan to use the latest data science tools to not only find more pieces, but also help researchers understand how those pieces fit together, including genes and other risk factors.”
But the experts caution that their study, which relied on electronic medical records rather than biological samples, merely describes correlations and does not prove cause-and-effect.
The study’s weaknesses are many.say the experts. The highlight is that the pairings are just associations; that is, they do not prove that viruses are causing brain diseases. There may be genetic reasons for someone to be more susceptible to both viruses and Parkinson’s, for example. And it’s likely that other environmental exposures also play a role in causing neurodegenerative diseases.
«There is a lot of work to be done to try to mechanistically link viral exposure and risk of neurodegenerative diseases.» admits Singleton.
In fact, a key part of the authors’ analysis undermines the notion that viruses trigger disease, Cornelia van Duijn, a genetic epidemiologist at Oxford University, told Science magazine.
Pairings are just associations; that is, they do not prove that viruses are causing brain diseases
As part of the study, the team used the Finnish data to examine the strength of the association for each virus-disease pair at 1, 5 and 15 years after infection. Because neurodegenerative diseases take years or decades to develop, one might expect the highest risk after 15 years. But the authors found the opposite: For virtually all couples, the elevation in risk was greatest one year after infection and decreased over time.
“That’s usually a red flag for epidemiologists,” says van Duijn, indicating that viral infections might not be causing the disease, but rather a byproduct of it. It is known, he says, that in the years leading up to a dementia diagnosis, for example, people become “metabolically and immunologically a disaster».
Furthermore, the authors relied on diagnoses from electronic medical records, meaning they only identified viral infections that made people sick enough to see their doctor or end up in the hospital. That could cause the team to miss thousands of infections that caused few or no symptoms, potentially skewing the results.
Also, noted Alberto Ascherio, an epidemiologist at the Harvard TH Chan School of Public Health and lead author of the 2022 “Science” article, diagnosis codes in health record databases can be misleading. A doctor may use an MS code when ordering a test for that disease, for example; after the test returns a negative result, the code may remain in the registry. The study “actually looking for correlations in a database that was obviously not designed to address these questions, a big limitation here» says Ascherio.
Even so, Ascherio stresses that “this is a topic that definitely deserves more attention, more research that could have important implications in terms of public health.”