Alzheimer's disease: Study of nearly 500,000 people confirms virus involvement

A study of nearly 500,000 people confirms a link between viral infections and some neurodegenerative diseases. One of the most significant associations is with viral encephalitis, which is thought to increase the risk of later developing Alzheimer's disease by 20-fold. On the other hand, pneumonia is strongly associated with the risk of later developing dementia, Parkinson's disease, or amyotrophic lateral sclerosis (ALS).

Neurodegenerative diseases are disabling conditions that usually occur quite late in life. However, despite decades of research in this area, their pathophysiological mechanisms remain largely unclear, which greatly complicates the development of effective treatments.

Various a priori unrelated risk factors have been proposed, ranging from genetics to gut dysbiosis, chronic stress, fungal and viral infections. “Neurodegenerative diseases are a group of diseases for which there are very few effective treatments and many risk factors,” explains Andrew B. Singleton from the Center for Alzheimer's Related Dementia (CARD) in the US.

Recent studies, in particular, have confirmed a long-suspected link between an increased risk of developing multiple sclerosis (MS) and previous Epstein-Barr virus (EBV) infection. Other studies involving autopsies of brain tissue have shown a link between the herpes simplex virus and Alzheimer's disease. These results show that scientists have been reasonably looking for individual associations between neurodegenerative diseases and specific viruses for decades.

To support these studies, Singleton and colleagues proposed a different approach by combining all possible associations in one study. “Our findings support the idea that viral infections and associated inflammation in the nervous system may be common—and possibly preventable—risk factors for these types of [neurodegenerative] diseases,” Singleton says. The results of this study provide several key pieces to complete the puzzle of the mechanisms of several neurodegenerative diseases.

Viral encephalitis increases the risk of developing Alzheimer's disease by 20 times

The new study, detailed in the journal Neuron, examined the medical records of 300,000 people registered in the Finnish biomedical database FinnGen. The study protocol included identifying individuals with one of the following 6 neurodegenerative disease diagnoses: Alzheimer's disease, ALS, generalized dementia, multiple sclerosis, Parkinson's disease, or vascular dementia. The study then looked to determine whether these people had previously been hospitalized for a viral infection, while hospitalizations due to COVID-19 were not included. In the second stage, a second series of comparative studies was carried out, including 100,000 records from UKBiobank (an English biomedical database).

The first series of studies identified 45 significant associations, while the second reduced this number to 22. Of all neurodegenerative diseases, the largest number of associations was found in generalized dementia, which in particular was associated with six different viral infections. These include viral encephalitis, viral warts, all types of influenza and viral pneumonia. A notable link has been found between viral encephalitis and Alzheimer's disease: People who contract the infection are at least 20 times more likely to develop the disease later in life. Pneumonia is also associated with a number of diseases, including dementia, Parkinson's disease and ALS.

It is important to note that viral infections are not a simple cold, but moderate to severe cases that require hospitalization or at least medical attention. According to the research team, 80% of the viruses identified in the study are able to cross the blood-brain barrier and trigger an inflammatory immune response. However, it should be noted that a cause-and-effect relationship has not been proven.

However, these results suggest that some vaccines may reduce the risk of developing neurological disease. In addition, a more detailed analysis of the 16 common associations identified in the FinnGen and UKBioBank data suggests that the risk posed by certain viruses is decreasing over time. While risks remained high one year after viral infection, only 6 of these associations remained significant 5–15 years after infection.