Viral Infection in Middle Age Correlates with Later Dementia Risk

A range of evidence suggests that persistent viral infection contributes to the risk of suffering neurodegenerative conditions such as Alzheimer's disease. This may be due to mechanisms relating to amyloid-β accumulation, in its role as an anti-microbial peptide, a part of the innate immune system. It may have more to do with lasting chronic inflammation subsequent to infection. Researchers here note another addition to the epidemiological data on this topic, in this case linking severe infections requiring hospitalization with later dementia risk. The effect sizes here are large and last for a long time following infection, but one might wonder how much of this relates to the degree of age-related immune dysfunction and other impacts of aging that lead from infection to hospitalization versus being able to work through it with clinical visits and over the counter medication only.

Previous research suggested infection with HSV increases a person's risk of developing Alzheimer's disease (AD). Likewise, someone who caught Epstein-Barr virus (EBV), which causes mononucleosis, is a whopping 32-fold more likely to develop multiple sclerosis (MS). Now, researchers have analyzed medical records from 344,000 people from the Finnish nationwide biobank, FinnGen, and 106,000 in the U.K. Biobank. All participants were of European ancestry and older than 60 at baseline. About 405,500 were healthy, while 44,500 had been diagnosed with an NDD: 11,650 with AD, 2,750 with vascular dementia, 18,700 with all-cause dementia, 7,200 with Parkinson's disease, 840 with amyotrophic lateral sclerosis, and 3,500 with multiple sclerosis.

Researchers compared NDD diagnosis to prior hospitalization with 32 common viral illnesses, including flu, pneumonia, viral warts, chickenpox/shingles, viral encephalitis, and meningitis. Viral exposure was based on hospital billing codes, so the researchers could not say whether it was the infection or something else that sent a person to the hospital. Any one of 12 of the illnesses correlated with a higher incidence of any of the six NDDs in both databanks. Notably, most of these viral illnesses are caused by neurotropic viruses - those that are able to get into the central nervous system (CNS) and into neurons. These include influenza viruses, HSV, the herpes zoster virus that causes chickenpox/shingles, various enteroviruses that cause meningitis, and EBV.

Which viral illness posed the greatest NDD risk? People who had had viral encephalitis were 31 times more likely to develop AD and 40 times likelier to have dementia of any kind than were people not hospitalized for infection. Likewise, AD risk jumped a whopping 62-fold after meningitis. And it was not just infections of the brain. People hospitalized for a viral intestinal infection had three to five times the risk of developing AD or vascular dementia. Viral hepatitis tripled PD risk, while herpes zoster boosted the likelihood of developing vascular dementia and MS two- to sixfold.

Since infections are typically acute and neurodegenerative disease can advance slowly over years or decades, researchers wondered if the risk for NDDs wanes after infection. They found that it was highest the first year, then fell over 15 years. For example, hazard ratios for all-cause dementia slid from 83 within a year of viral encephalitis to 24 over the next four years, then to five by year 15. What does this all mean for middle-aged folks? Researchers noted that all these cases were in people who had severe symptoms and, therefore, didn't represent someone who rode out the flu or shingles at home. Preventing severe viral illness by getting vaccinated against the flu, pneumonia, or shingles may partially protect someone from getting an NDD. Indeed, a previous analysis concluded that people who got flu or pneumonia shots were less likely to get AD than the unvaccinated.