NIH researchers have found that at least 22 viral diseases are associated with an increased risk of subsequent neurodegenerative disease.
Using data from the UK and Finland, Mike Nalls, Ph.D., of the NIH Center for Alzheimer’s Disease and Related Dementias, and co-authors identified 45 viral exposures associated with an increased risk of dementia or other neurodegenerative diseases. We identified and reproduced 22 of these associations. .
The greatest effect association was between exposure to viral encephalitis and Alzheimer’s disease, researchers reported neuron.
After data from the 1918 influenza pandemic suggested a possible link between H1N1 influenza A and post-encephalitic parkinsonism, researchers have debated a possible relationship between the virus and neurodegenerative diseases. In recent years, studies have linked the herpes virus to Alzheimer’s disease and the Epstein-Barr virus to multiple sclerosis (MS).
“After reading the Epstein-Barr virus study, I realized that for years, scientists had been looking for links between individual neurodegenerative diseases and specific viruses,” Nulls said. said in a statement.
“That’s when we decided to try a different, more data science-based approach,” he added. “By using medical records, we were able to systematically search for all possible links in one go.”
Nalls and colleagues evaluated time-series data of approximately 335,000 individuals in a discovery cohort of people participating in FinnGen, Finland’s national biobank. The researchers searched for diagnoses of Alzheimer’s disease, amyotrophic lateral sclerosis, dementia, multiple sclerosis, Parkinson’s disease, or vascular dementia and found that patients with those diagnoses led to hospitalization. Identified if you had a previous viral infection. Hospitalizations due to SARS-CoV-2 were not included in the study.
Researchers found 45 significant associations between a neurodegenerative disease diagnosis and previous viral infections. Some exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. We replicated 22 of these associations using cross-sectional data from approximately 106,000 UK Biobank participants aged 60 and over.
Dementia was most associated with exposure to six viruses: viral encephalitis, viral warts, other viral illnesses, all influenza, influenza and pneumonia, or viral pneumonia. was
The highest hazard ratio was seen for the relationship between viral encephalitis and Alzheimer’s disease: 30.72 (95% CI 11.84-79.68) in the discovery cohort and 22.06 odds ratio (95% CI 5.47-88.94) in the replication cohort.
“To put this in context, at FinnGen, 24 of 406 cases of viral encephalitis developed Alzheimer’s disease (5.9%), compared to the general prevalence of Alzheimer’s disease in the same population of less than 3%. higher than that.” Nalls and colleagues wrote:
Severe influenza cases were associated with the broadest range of risks, and exposure to influenza and pneumonia was associated with diagnosis of all neurodegenerative diseases except MS. Across all FinnGen follow-up periods, exposure to Epstein-Barr virus was associated with MS risk (HR 3.92, 95% CI 2.57-6.00).
Sixteen associations were at increased risk of being diagnosed with a neurodegenerative disease within 1 year of infection. Six associations were significant if the infection occurred 5 to 15 years before he was diagnosed.
“The overwhelming majority of replicated associations involved viruses that are commonly considered neurotrophic (81%), which is due to the fact that the virus travels through peripheral nerves or crosses the blood-brain barrier. It means it can penetrate the central nervous system,” the researchers observe. “This suggests that these viruses contribute to inflammation in the brain, thereby reducing the risk of neurodegenerative disease by lowering cognitive reserve (the resilience to neurodegeneration and the ability to perform complex mental tasks). It suggests that it can be increased.
The results raised the idea that vaccination could help reduce the risk of neurodegenerative diseases in some people.
“Keep in mind that the individuals we investigated did not have colds. Their infections made them very sick and they had to go to the hospital,” Nulls noted. Nevertheless, the fact that commonly used vaccines reduce the risk or severity of many of the viral diseases observed in this study suggests that the risk of neurodegenerative diseases may also be reduced. raise it.”
The researchers acknowledge that the study had some limitations. “Because we were limited to what was available in our discovery set, we were unable to investigate the relationship between exposure to the virus and age at onset of neurodegenerative disease,” Nalls and colleagues said.
In some cases, reverse causality may have occurred. Furthermore, the UK Biobank data were only cross-sectional.
This study was funded by the Intramural Research Program of the National Institute on Aging.
Nalls is a member of the Scientific Advisory Board of Clover Therapeutics and an advisor to Neuron23. The researchers’ participation in this project was part of a competitive contract awarded to Data Tecnica International by the NIH.
Source: Levine KS, et al. Viral Exposure and Neurodegenerative Disease Risk in the National Biobank. Neuron 2023; DOI: 10.1016/j.neuron.2022.12.029.