Big study uncovers 22 links between viral infections and brain disease
New research looking at health records from nearly half a million people has identified 22 different associations between viral infections and neurodegenerative diseases. Influenza, encephalitis and other viral infections all were linked to increased rates of brain diseases such as Parkinson's, Alzheimer's and MS.
The idea that viral infections can play a role in the development of neurodegenerative disease isn't particularly new. Back in the 1950s microbial infections were suggested to be the source of many neurodegenerative diseases, with herpes in particular hypothesized to be deeply associated with the development of Alzheimer's.
Although the idea sat on the fringes of neuroscience for decades, it has recently been drifting into the mainstream after a handful of key studies uncovered strong, novel evidence. In particular, a study published early in 2022 presented robust causal evidence linking the development of multiple sclerosis (MS) to infection with the Epstein-Barr virus (EBV).
“After reading the Epstein Barr virus study we realized that for years scientists had been searching, one-by-one, for links between an individual neurodegenerative disorder and a specific virus,” said senior author Michael Nalls, explaining the genesis of this new investigation. “That’s when we decided to try a different, more data science-based approach. By using medical records, we were able to systematically search for all possible links in one shot.”
The first part of the study looked at 300,000 medical records, focusing on new diagnoses for either Alzheimer’s disease, ALS, generalized dementia, multiple sclerosis, Parkinson’s disease, or vascular dementia. For each new neurodegenerative disease diagnosis the researchers looked at whether the patient had any record of a preceding viral infection.
After initially detecting 45 potential associations between viral infections and brain disease, the researchers tested those links in another database of 100,000 health records. Here they homed in on 22 specific associations.
"The largest effect association was between viral encephalitis exposure and Alzheimer’s disease," the researchers write in the study. "Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection."
The findings certainly add to our growing understanding of the relationship between viral infections and neurodegenerative disease but they also raise some important questions that need to be answered. The records could only track associations between infection and brain disease up to 15 years, for example, so there is no insight into potential long-term links.
Perhaps most significantly, the study found most links between brain disease and viral infections were strongest in the immediate year following an infection. The more time that passed after a viral infection, the weaker the links that were detected.
This means it is possible viral infections are only accelerating a degenerative process that is already underway, and not triggering any initial development. Or, as the researchers speculate, it could be possible the early pre-symptomatic stages of neurodegenerative disease cause a type of immune dysregulation that makes a person more predisposed to suffering from severe viral infections.
"A significant body of research supports the notion that the neurodegenerative process begins many (10–20) years before diagnosis," the researchers write. "It is possible, for example, that a hospitalization for influenza with pneumonia that is recorded as 5 years before an NDD diagnosis could actually be occurring 5 years after the degenerative process has already begun. However, if patients are infected with more viruses as their bodies suffer the effects of an NDD before diagnosis, we might expect to see even more cases of a virus after diagnosis."
Nalls said the findings do raise the possibility that broader deployment of common vaccines could potentially reduce rates of neurodegenerative disease. If neurodegenerative disease is primarily accelerated by severe viral infections then vaccinations known to reduce the severity of illness could slow things down for many people. This effect has been somewhat detected in studies linking a reduced risk of Alzheimer's disease in elderly subjects receiving annual flu vaccinations.
“Keep in mind that the individuals we studied did not have the common cold," said Nalls. "Their infections made them so sick that they had to go to the hospital. Nevertheless, the fact that commonly used vaccines reduce the risk or severity of many of the viral illnesses observed in this study raises the possibility that the risks of neurodegenerative disorders might also be mitigated.”
The new study was published in the journal Neuron.