| Neuroepidemiology  

Virus exposure and neurodegenerative disease risk across national biobanks

Several viral exposures were recently associated with the risk of neurodegenerative diseases, with the greatest effect association observed between viral encephalitis and Alzheimer's disease.

Recent evidence has demonstrated an association between Epstein-Barr virus (EBV) infection and a higher risk of multiple sclerosis (MS) (1). COVID-19 pandemic has created additional concerns regarding the cognitive and other neurological consequences of coronavirus infection.

In this context, a recent study aimed to examine putative links between viral exposures and the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), generalized dementia, vascular dementia, Parkinson’s disease (PD), and multiple sclerosis (MS) (2).

Time series data were derived from the FinnGen, a Finnish biobank (data for over 300,000 individuals), and cross-sectional data were applied for replication in the UK Biobank (data for almost 500,000 individuals).

The discovery cohort analysis demonstrated that 45 viral exposures were significantly associated with increased risk of neurodegenerative disease, and replication indicated 22 of these associations.
In particular, the association with the largest effect was observed between viral encephalitis exposure and AD. Influenza with pneumonia was associated with five of the six neurodegenerative diseases studied. Dementia displayed the most replicated associations after correction of multiple testing. The link between Epstein-Barr and MS was also replicated. In some of these cases, the exposures were associated with a higher risk of neurodegeneration up to 15 years after infection.

Most associations included viruses considered neurotrophic, suggesting that these viruses may increase the risk of neurodegeneration by lowering cognitive reserve, via neuroinflammation.
Since vaccines are currently available for at least some of the related viruses identified, preventive measures through vaccination may at least partially mitigate the risk of neurodegenerative diseases.

Key Points:

• 45 viral exposures were significantly associated with increased risk of neurodegenerative diseases, and replication indicated 22 of these associations
• The association with the largest effect was observed between viral encephalitis exposure and AD
• In some cases, the exposures were associated with a higher risk of neurodegeneration up to 15 years after infection
• Most associations included viruses considered neurotrophic, suggesting that these viruses may increase the risk of neurodegeneration by lowering cognitive reserve, via neuroinflammation
• Preventive measures through vaccination may at least partially mitigate the risk of neurodegenerative diseases

References:

  1. Bjornevik K., Cortese M., Healy B.C., Kuhle J., Mina M.J., Leng Y., Elledge S.J., Niebuhr D.W., Scher A.I., Munger K.L., Ascherio A., Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis., Science. 2022; 375: 296-301
  2. Levine KS, Leonard HL, Blauwendraat C, Iwaki H, Johnson N, Bandres-Ciga S, Ferrucci L, Faghri F, Singleton AB, Nalls MA. Virus exposure and neurodegenerative disease risk across national biobanks. Neuron. 2023 Jan 11:S0896-6273(22)01147-3. doi: 10.1016/j.neuron.2022.12.029. Epub ahead of print.

Co-Author:

Melinda Magyari, Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Dániel Bereczki, 1./ Department of Neurology, Semmelweis University, Budapest, Hungary 2./ MTA-SE Neuroepidemiological Research Group ELKH, Budapest, Hungary

Publish on behalf of the Scientific Panel on Neuroepidemiology