At least 22 viral infections were associated with an increased risk of neurodegenerative diseases, including Alzheimer's and dementia, according to a new study published in Neuron. However, the researchers suggest that vaccination against these viruses may be a way to reduce this risk.

Certain viral infections may be linked to neurodegenerative diseases

For the study, researchers assessed time-series data from around 350,000 people who participated in FinnGen, a nationwide biobank in Finland. Patients who had been diagnosed with Alzheimer's, amyotrophic lateral sclerosis, dementia, multiple sclerosis (MS), Parkinson's disease, or vascular dementia were identified.

Once these patients were identified, researchers determined whether any patients had had a previous viral infection that resulted in a hospitalization. Patients who had been hospitalized for COVID-19 were not included in the study.

Overall, the researchers found 45 significant associations between a previous viral infection and being diagnosed with a neurodegenerative disease, with some exposures associated with an increased risk up to 15 years after an initial infection. Using cross-sectional data of roughly 106,000 participants over the age of 60 from the U.K. Biobank, the researchers were able to replicate 22 of these associations.

The association with the highest hazard ration was viral encephalitis and Alzheimer's at 30.72. "To place this in context, we see in FinnGen, 24 of 406 viral encephalitis cases went on to develop Alzheimer's disease (5.9%); this is higher than the general prevalence of Alzheimer's disease in the same population at less than 3%," the researchers wrote.

The disease that had the most associations was dementia, which had links to six different viruses: encephalitis, viral warts, all influenza, influenza and pneumonia, viral pneumonia, and other viral diseases.

In addition, severe influenza cases were associated with the widest range of risks, while exposure to both influenza and pneumonia was associated with every neurodegenerative diagnoses except for MS. The Epstein-Barr virus was most associated with MS risk.

In 16 associations, the risk of a neurodegenerative diagnosis was high within a year of infection, and in six associations, the risk of a diagnosis was high if the infection had occurred between five and 15 years prior.

"The overwhelming majority of replicated associations include viruses commonly considered neurotrophic (81%), which means they can invade the central nervous system through peripheral nerves or by crossing the blood-brain barrier," the researchers wrote. "This suggests that these viruses may increase neurodegenerative disease risk by lowering cognitive reserve (resilience to neurodegeneration and the ability to carry out complex mental tasks) by contributing to inflammation in the brain."

According to the researchers, the study's findings suggest that vaccination could potentially reduce the risk of neurodegenerative diseases for some people.

"Keep in mind that the individuals we studied did not have the common cold. Their infections made them so sick that they had to go to the hospital," said Mike Nall, one of the study's authors from the NIH Center for Alzheimer's and Related Dementias. "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."

However, the researchers also acknowledged that the study had several limitations, including that the U.K. Biobank data was cross-sectional only and that reverse causality could have occurred. "We were unable to investigate the relationship between viral exposure and age at onset of a neurodegenerative disease, as we were limited by what was available in our discovery set," they wrote. (George, MedPage Today, 1/30; Levine et al., Neuron, 1/19)