At least 22 viral illnesses were linked with an increased risk of subsequent neurodegenerative disease, US National Institutes of Health researchers found, with viral encephalitis and Alzheimer’s disease showing the strongest links, Medpage Today reports.
Using data from the UK and Finland, Mike Nalls, PhD, of the NIH Centre for Alzheimer’s and Related Dementias in the US, and co-authors identified 45 viral exposures that were tied to an increased risk of dementia or other neurodegenerative diseases and replicated 22 of these associations, they wrote in the journal Neuron.
After data from the 1918 flu pandemic suggested H1N1 influenza A and post-encephalitic Parkinsonism could be linked, researchers have debated possible relationships between viruses and neurodegenerative diseases. In recent years, studies have reported links between herpes viruses and Alzheimer’s and between Epstein-Barr virus and multiple sclerosis (MS).
“After reading the Epstein-Barr virus study, we realised that for years, scientists had been searching, one by one, for links between an individual neurodegenerative disorder and a specific virus,” Nalls said. “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.”
Nalls and colleagues assessed time-series data for about 335 000 individuals in a discovery cohort of people participating in FinnGeno, a nationwide Finnish biobank. The researchers searched for diagnoses of Alzheimer’s disease, amyotrophic lateral sclerosis, dementia, MS, Parkinson’s disease, or vascular dementia, then identified whether patients with those diagnoses had a previous viral infection that led to hospitalisation. SARS-CoV-2 hospitalisations were not included in the study.
The researchers found 45 significant associations between a neurodegenerative disease diagnosis and a previous viral infection. Some exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. Using cross-sectional data from about 106 000 UK Biobank participants over 60, they replicated 22 of these associations.
Dementia had the most associations, with links to six different virus exposures: viral encephalitis, viral warts, other viral diseases, all influenza, influenza and pneumonia, or viral pneumonia.
The highest hazard ratio was seen for the relationship between viral encephalitis and Alzheimer’s: 30.72 for the discovery cohort (95% CI 11.84-79.68), with an odds ratio of 22.06 for the replication cohort (95% CI 5.47-88.94).
“To place this in context, we see in FinnGen, 24 of 406 viral encephalitis cases went on to develop Alzheimer’s (5.9%); this is higher than the general prevalence of Alzheimer’s in the same population at less than 3%,” they wrote.
Severe influenza cases were linked to the widest range of risks, and influenza and pneumonia exposures were associated with all neurodegenerative disorder diagnoses except MS. Across all follow-up durations in FinnGen, Epstein-Barr viral exposure was associated with MS risk (HR 3.92, 95% CI 2.57-6.00).
In 16 associations, the risk of being diagnosed with a neurodegenerative disorder was high within one year of infection. Six associations were significant if the infection occurred five to 15 years before the diagnosis.
“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 observed.
“This suggests 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.”
The results raised the idea that vaccination may help reduce neurodegenerative disease risk for some people.
“Remember that the individuals we studied did not have the common cold. Their infections made them so sick they had to go to the hospital. Nevertheless, 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 study had several limitations, the researchers conceded. “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 noted.
Reverse causality may have occurred in some cases. In addition, UK Biobank data were cross-sectional only.
Study details
Virus exposure and neurodegenerative disease risk across national biobanks
Kristin Levine, Hampton Leonard , Cornelis Blauwendraat, Faraz Faghri, Andrew Singleton, Mike Nall.
Published in Neuron on 18 January 2023
Highlights
• Identified 45 pairs of viral exposures associated with increased risk of NDDs
• Replicated 22 of the viral exposures/NDD pairings
• Replicated the previously reported Epstein-Barr and multiple sclerosis association
• Follow-up shows significantly elevated risk of NDD years after viral exposure
Summary
With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk. Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations. The largest effect association was between viral encephalitis exposure and Alzheimer’s disease. 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. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.
See more from MedicalBrief archives:
Flu and pneumonia vaccinations may reduce Alzheimer’s risk
Epstein-Barr virus may be leading cause of Multiple Sclerosis – Harvard cohort study
Misdiagnosis of multiple sclerosis found to be common
Corroborating the role of herpes simplex virus in Alzheimer’s