Massive health-records review links viral illnesses to brain disease

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

An analysis of nearly 450,000 electronic health records has found an association between infection with influenza and other common viruses and a higher risk of developing neurodegenerative conditions such as Alzheimer’s or Parkinson’s disease later in life. But the researchers caution that the data show only a possible connection, and it is still unclear whether or how the infection begins.

Published analysis in neuron on 19 January1, found at least 22 links between viral infections and neurodegenerative diseases. Some viral exposures were associated with an increased risk of brain disease for up to 15 years after infection.

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

mining health record

This is not the first time the virus has been linked to neurodegenerative disease. Infection with a type of herpes virus has been linked to the development of Alzheimer’s.2, 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 previous studies only examined a single virus and a specific brain disease.

To understand whether viruses are associated with brain diseases more broadly, Kristin Levin, a biomedical data scientist at the US National Institutes of Health Center for Alzheimer’s-related Dementia in Bethesda, Maryland, and her colleagues looked at hundreds of examples. Thousands of medical records analyzed. In which one person had both a viral infection and a brain disease on file.

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

One of the strongest associations was between viral encephalitis, a rare inflammation of the brain that can be caused by several types of virus, and Alzheimer’s. People with encephalitis were almost 31 times more likely to develop Alzheimer’s in later life, compared to people who did not have encephalitis. Most other associations were more modest: People who got pneumonia were four times more likely to develop Alzheimer’s than people who didn’t get the flu with pneumonia. There was no pairing that suggested a protective link between viral infection and brain disease.

“I’m very excited that they’re expanding this research more broadly than other studies,” says Kristen Funk, a neuroimmunologist at the University of North Carolina, Charlotte, who studies the link between herpesviruses and Alzheimer’s. .

data loopholes

Kjetil Bjornevik, an epidemiologist at the Harvard TH Chan School of Public Health in Boston, Massachusetts, and an author on the Epstein-Barr paper Science, commends Levin and his colleagues for calling more attention to the role of viral infections in brain diseases. But he cautioned that their approach using medical records “may be problematic” because they only analyzed infections that were severe enough to warrant a visit to a health practitioner. He says that keeping mild infections in mind can weaken the relationship.

The data is obtained almost exclusively from people of European ancestry, says Funk, which means the findings may not apply to the larger global population. In addition, she says, outside Europe, “some viruses are more prevalent,” such as Zika or West Nile virus, so the analysis may have missed links between those pathogens and brain disease. Levine acknowledges the limits of the analysis; The team worked with the data available, she says.

Bjornevik says these limitations also underscore the difficulty of whether viral infection causes neurodegenerative disease, or whether the disease makes a person more vulnerable to infection. To make it even more intriguing, the authors found that the more time elapsed between infection and diagnosis of brain disease, the weaker the link. The body is known to start changing before brain disease symptoms develop and are diagnosed4, so it’s hard to determine which is the cause, he says. Another plausible theory is that these viral infections may 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 connection between viral infection and brain disease, it could provide health officials with a concrete way to delay the onset of neurodegenerative disease. Vaccines exist for many of these viruses, says Van Duijn. Because many types of dementia are diagnosed late in life – close to average life expectancy – if physicians can postpone the onset of the disease by a few years, it could mean that many people never develop the disease. Can’t develop, she moves on.

“It’s not very clear that the infections are causing the brain disease,” she says. But viral infections are not pleasant, and if there is a link to brain disease, “I think we should give people the means to stop them.”

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