Viral exposure may increase the risk of developing neurodegenerative diseases (NDDs) in the future among older adults, according study findings published in the journal Neuron.

Recent research has found that prior infection with the Epstein-Barr virus (EBV) increased risk for multiple sclerosis (MS). To investigate whether infection with other viruses may have similar risks for NDDs, researchers from the National Institutes of Health in the United States sourced data for this study from the FinnGen longitudinal cohort (discovery) and the UK Biobank (UKB; replication). A total of 73 viral endpoints and NDD pairs were evaluated.

In the FinnGen and UKB datasets, a total of 16,499 and 2200 dementia, 9301 and 2342 Alzheimer disease (AD), 4235 and 2998 Parkinson disease (PD), 2335 and 430 vascular disease, 2182 and 1349 MS, and 483 and 357 amyotrophic lateral sclerosis (ALS) cases were compared with 309,154 and 96,390 control individuals, respectively.

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As MS and EBV had previously been linked, this association was tested as a positive control in these data. This association was replicated in the FinnGen data (hazard ratio [HR], 26.5; 95% CI, 3.7-191.6; P =.001) but not in the UKB data.

Overall, 45 viral and NDD pairs were significant in the FinnGen dataset, of which 22 were replicated in the UKB. The association with the most evidence was encephalitis and AD (FinnGen: HR, 30.72; P =1.89×10-12; UKB: HR, 22.06; P =1.37×10-5), in which 24 of the 406 (5.9%) FinnGen cases of viral encephalitis developed AD whereas the rate of AD among non-encephalitis FinnGen control individuals was <3%.

The NDD that was associated with the greatest number of viral infections was dementia, in which prior influenza, influenza and pneumonia, viral pneumonia, viral encephalitis, viral warts, and other viral diseases all associated with increased dementia risk.

The viral infection that was associated with the greatest number of NDDs was influenza and pneumonia, in which individuals who developed AD, ALS, dementia, PD, and vascular disease were all more likely to have had influenza and pneumonia.

The relationship between viral infection and NDDs appeared to be bidirectional. Eight pairs remained significant in both directions (ie, viral infection followed by NDD diagnosis and NDD diagnosis followed by viral infection) with a 1-year lag period, 10 pairs were significant with a 5-year lag period, and 2 pairs were significant with a 15-year lag period. The 2 pairs with the most long-lasting bidirectional effects were AD and influenza and dementia and Bell palsy.

“In light of the current coronavirus pandemic, our results illustrate the need to take seriously the reports of concomitant neurological symptoms accompanying viral exposures and monitor at risk patients to discover if they will be at higher risk of NDDs in the future,” the researchers noted. They added that “The findings reported here cover multiple NDDs from two different biobanks, and previous research supports the described associations between viral infection and NDD risk, suggesting that virus/NDD associations are worthy of further investigation.”

This study may have been limited by the granularity of viral exposure which could have added noise into the analyses.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Levine KS, Leonard HL, Blauwendraat C, et al. Virus exposure and neurodegenerative disease risk across national biobanks. Neuron. Published online January 11, 2023. doi:10.1016/j.neuron.2022.12.029

This article originally appeared on Neurology Advisor