Longevity Briefs: Are Viruses Key Players In Dementia?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: For a long time, scientists have speculated that some viruses could be at least partly responsible for neurological diseases such as multiple sclerosis and dementia. Viruses that are able to infect cells of the central nervous system can contribute to inflammation in the brain, which is thought to be an important driver of neurodegenerative diseases like Alzheimer’s. This theory is a matter of some controversy, however, as it’s practically impossible to prove that a viral infection caused a neurological condition, especially since such conditions may emerge years or decades after the infection itself.

What did the researchers do: In this study, researchers analysed medical records from 344 000 people from the Finnish nationwide biobank (FinnGen), and 106 000 people from the U.K. Biobank. All participants were at least 60 years old, and around 45 000 had been diagnosed with a neurodegenerative disease. Researchers then looked at whether participants had previously been in hospital with any of 32 common viral illnesses (though data on whether their hospital visit was caused by the viral infection or something else was not available).

Key takeaway(s) from this research:

• Hospitalisation with 12 types of viral infection, including influenza (flu), were correlated with increased risk of neurodegenerative disease.
• Most of these were viruses with the ability to infect the central nervous system, but intestinal infections were also correlated with neurodegenerative disease.
• For some infections, risk remained increased for 15 years following hospitalisation.
• There is some evidence that influenza vaccines could reduce dementia risk.

The researchers identified 12 types of viral infection for which hospitalisation was correlated with increased risk of neurodegenerative disease. The strongest association was for viral encephalitis, which is most commonly caused by herpes simplex viruses. FinnGen participants hospitalised with viral encephalitis were about 30 times more likely to develop Alzheimer’s disease than people not hospitalised with said infection. Pneumonia due to influenza, meanwhile, was significantly associated with increased risk of five neurodegenerative diseases (Alzheimer’s, amyotrophic lateral sclerosis, dementia, Parkinson’s and Vascular dementia).

The increased risk was greatest within a year after infection, but for some infections risk remained elevated for 15 years post-hospitalisation. While most of the implicated viruses were neurotropic (meaning they infect the central nervous system), researchers also found a roughly 3-fold increase in Alzheimer’s risk for those hospitalised with unspecified intestinal infections, which aligns with what we think we know about the links between the gut, the immune system and the brain. 

Although some of the associations in this study are very strong, it’s unlikely that all of this association is causal. If someone is hospitalised with influenza, then they are already likely to be frailer or have a dysfunctional immune system compared to someone who recovers without hospital care. These differences could explain their increased dementia risk. With that being said, studies suggest that influenza and other viruses can cause neurodegeneration in mice, and there are plausible mechanisms for this to happen in humans too. If these viruses really do cause dementia in humans, the most effective prevention strategy would simply be to increase the rate of vaccination, which can significantly reduce hospitalisation rates. There is indeed evidence suggesting that people who are vaccinated against influenza get less dementia, though once again, these studies have yet to prove anything more than correlation.