Viral infections earlier in life could *possibly* predict Alzheimer's disease later in life

Photo by Brittany Colette

A recent correlational study looked at the occurrence of viral diseases in patients, and how this could predict Alzheimer’s later in life. If they are right about this, it would mean that viral infections may be at least partly to blame for the disease.

The struggle to fight Alzheimer’s disease

Scientists have really struggled to identify the causes of Alzheimer’s or to truly understand the disease process. Not understanding the disease has made it very difficult to develop useful treatments. Two recently FDA-approved Biogen drugs for treating Alzheimer’s by reducing the quantity of amyloid plaques in the brain have been a bust, as has the theory that amyloid plaques cause the disease. Instead, the plaques are probably a mere byproduct of the disease and the medications solve the wrong problem.

Do viral infections lead to Alzheimer’s disease?

Let’s dive in to the study in question (Levine et al. 2023). By the way, the study is a pre-print that has not yet been through peer-review, which is fine but important to declare.

But the answer to the question is “maybe.” Why?

The study is correlational. Two different things could be going on and it’s not very easy to tell which one it is:

1. Viral infection —> Alzheimer’s disease later in life

2. Generally poor health (seen or unseen) —> viral infection and Alzheimer’s disease later in life

So it could be that these viral infections are causing Alzheimer’s disease down the road but it could also be the case that people who have underlying health issues are susceptible to both viral infections and Alzheimer’s disease. We don’t really know for sure which it is (or if it’s a little of both) because it’s correlational.

The connection appears to be greater between viruses that affect the brain and Alzheimer’s disease. This seems intuitive enough. But again, it could be that there is a vulnerability in the brain that allows for both the viral infection and Alzheimer’s disease to occur. Even in the most extreme case the differences are not that great:

24 of 406 viral encephalitis cases went on to develop AD (5.9%); this is higher than the general prevalence of AD in the same population at less than 3%.

Also note that small sample size of 24 Alzheimer’s patients. Sometimes when you have small samples you see crazy numbers that would actually revert to the mean if we saw more data roll in. The total study had way, way more than 24 people but when you look at all of the sub-groups, the sample sizes for some of them are quite small making it difficult to know if viral encephalitis in this case really is a strong predictor of Alzheimer’s.

Conclusions

People who fall ill with severe viral infections at mid-life are more likely to acquire Alzheimer’s disease later but we need more information to know if it’s causal. It could be that an underlying weakness allows both the viral infection and the Alzheimer’s disease to occur. The other thing to note is that we’re not talking big differences here. I should point out that there are a few research-supported ways to reduce the risk of cognitive decline later in life but avoiding viruses (if possible) may or may not be one of them. More research is needed.

References

Virus exposure and neurodegenerative disease risk across national biobanks

Kristin Levine, Hampton L. Leonard, Cornelis Blauwendraat, Hirotaka Iwaki, Nicholas Johnson, Sara Bandres-Ciga, Walter Koroshetz, Luigi Ferrucci, Faraz Faghri, Andrew B. Singleton, Mike A. Nalls

medRxiv 2022.07.08.22277373; doi: https://doi.org/10.1101/2022.07.08.22277373