Massive health records review links viral illnesses to brain disease

Colored scanning electron micrograph (SEM) of influenza (flu) viruses (blue) budding from a burst epithelial cell.

In this false-color scanning electron microscope image, influenza virus particles (blue) are poised to be released from a burst epithelial cell (red).Credit: Lennart Nilsson, Boehringer Ingelheim International GMBH, TT/SPL

An analysis of about 450,000 electronic health records has found a link between infections with influenza and other common viruses and an elevated risk of having a neurodegenerative disease like Alzheimer’s or Parkinson’s later in life. life. But the researchers warn that the data only shows one possible link, and it’s still unclear how or if the infections trigger the onset of the disease.

The analysis, published in neuron January 191, found at least 22 links between viral infections and neurodegenerative diseases. Some of the viral exposures were associated with an increased risk of brain disease up to 15 years after infection.

“It’s surprising how widespread these associations seem to be, both for the number of viruses and the number of neurodegenerative diseases involved,” says Matthew Miller, a viral immunologist at McMaster University in Hamilton, Canada.

Mining Health Records

This is not the first time that viruses have been linked to a neurodegenerative disease. Infection with a type of herpes virus has been linked to the development of Alzheimer’s disease2, for example. And a landmark study published in Science3 last year found the strongest evidence yet that the Epstein-Barr virus is linked to multiple sclerosis. But many of these earlier studies have only looked at a single virus and a specific brain disease.

To understand whether viruses are more broadly linked to brain diseases, Kristin Levine, a biomedical data scientist at the Center for Alzheimer’s Related Dementias at the US National Institutes of Health in Bethesda, Maryland, and her colleagues analyzed hundreds of thousands medical records to search for cases. in which a person had both a viral infection and a brain disease on record.

First, the team looked at the records of about 35,000 people with brain diseases and about 310,000 people without, from FinnGen, a large Finnish database that includes health information. The team found 45 significant links between infections and brain disease, then tested them against more than 100,000 records from another database, the UK Biobank. After this analysis, they were left with 22 significant matches.

One of the strongest associations was between viral encephalitis, a rare inflammation of the brain that can be caused by several types of viruses, and Alzheimer’s disease. People with encephalitis were about 31 times more likely to develop Alzheimer’s disease later in life than people who did not have encephalitis. Most of the other associations were more modest: people who had a flu episode that led to pneumonia were four times more likely to develop Alzheimer’s disease than people who did not develop flu with pneumonia. . Neither pairing suggested a protective link between viral infection and brain disease.

“I’m very excited that they’re extending this research beyond what other studies have looked at,” says Kristen Funk, a neuroimmunologist at the University of North Carolina, Charlotte, who studies the link between herpesviruses and Alzheimer’s disease.

Data gaps

Kjetil Bjornevik, an epidemiologist at the Harvard TH Chan School of Public Health in Boston, Massachusetts, and author of the Epstein-Barr article in Science, applauds Levine and his colleagues for bringing more attention to the role of viral infections in brain disease. But he warns that their approach of using medical records “could be problematic” because they only analyzed infections severe enough to warrant a visit to a medical professional. Considering milder infections could weaken the associations, he says.

The data also comes almost exclusively from people of European ancestry, which means the findings might not be applicable to the entire global population, Funk says. Also, she adds, outside of Europe “some viruses are more prevalent,” such as Zika or West Nile virus, so the analysis might have missed links between these pathogens and brain diseases. Levine recognizes the limits of analysis; the team worked with the available data, she said.

These limitations also underscore the difficulty of disentangling whether a viral infection leads to a neurodegenerative disease, or whether the disease makes a person more susceptible to infection, Bjornevik says. To make matters even trickier, the authors found that the longer the time between infection and diagnosis of brain disease, the weaker the link. The body is known to start changing years before symptoms of brain disease develop and a diagnosis is made.4, so it is difficult to determine what causes what, he adds. Another plausible theory is that these viral infections could accelerate molecular changes in the body that were already underway, says Cornelia van Duijn, a genetic epidemiologist at the University of Oxford, UK.

If future studies add more weight to the link between viral infection and brain disease, it could offer health officials a tangible way to delay the onset of neurodegenerative diseases. Vaccines exist for many of these viruses, van Dujin says. Because several types of dementia are diagnosed late in life – near the average life expectancy – if clinicians could delay the onset of the disease by even a few years, it could mean that many people may never develop the disease. illness, she adds.

“It’s not very clear that infections cause brain disease,” she says. But viral infections aren’t pleasant, and if there’s a link to brain disease, “I think we owe it to people to prevent it.”

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