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Severe infections are linked to increased risk of dementia

A new peer-reviewed study provides evidence of a potential link between certain severe infections and an increased risk of dementia. The study highlighted evidence that severe infections — from influenza and other viral infections to respiratory and skin conditions — may be linked to the development of dementia and Alzheimer’s disease.

The study also provided plausible mechanisms on how these infections could contribute to cognitive decline.

This post will review this new paper and explain how these infections might be linked to dementia.

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What is dementia and Alzheimer’s disease?

Before proceeding, it’s important to describe what we know about Alzheimer’s disease (AD). It is a chronic neurodegenerative disease that usually starts slowly and worsens over time. It accounts for 60-70% of dementia cases, even though the terms are sometimes used interchangeably. Alzheimer’s disease is a form of dementia. Other forms of dementia include Lewy body dementia, frontotemporal disorders, vascular dementia, and mixed dementia, which is a combination of two or more of the different forms of dementia.

Amyloid plaques (caused by amyloid beta, or Aβ), phosphorylated tau tangles (pTau), and neurofibrillary tangles are generally easily visible pathologies that can be observed by microscopic analysis of brain tissue from autopsies of those potentially afflicted by AD. These plaques and tangles seem to affect nerve functioning. Despite these observations, the precise pathophysiology, or development, of dementia or Alzheimer’s disease is not known.

Given that amyloid plaques are frequently found in patients with Alzheimer’s disease, extensive research is directed toward targeting these plaques as a potential means to mitigate the impact on nerves that contribute to AD. Despite our limited understanding of the causes of AD, there is speculation that genetics play a significant role, with numerous genes implicated in this relationship.

Since we have no clear understanding of the etiology and pathophysiology of AD, there are no effective treatments available today for the disease. There are some drugs that target the amyloid plaques, but they have yet to show a change in the course or outcomes of AD.

A couple of medications help manage some of the symptoms of the disease, but they are certainly not cures. There are several drugs at the very earliest stages of development that may hold out hope to treat the underlying disease.

One more thing that needs to be made clear. There are no biological tests for Alzheimer’s disease — usually, you can only find the amyloid plaques and other pathologies in post-mortem autopsies. Unfortunately. in the absence of an autopsy, clinical diagnoses of AD are “possible” or “probable”, based on other findings, such as memory tests and other methods.

In the United States, about 10.7% of seniors (≥65 years) currently have Alzheimer’s dementia, and the incidence of dementia and Alzheimer’s disease is expected to rise substantially in the coming decades due to population aging, making it imperative to identify modifiable risk factors that may help mitigate its impact. The economic burden of AD is expected to surpass $2.8 trillion by 2030.

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Infections and dementia paper

In a paper published on 14 August 2024 in the respected Nature Aging, Keenan A Walker, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, and colleagues examined proteins from individuals with an infection history in the Baltimore Longitudinal Study of Aging. The researchers identified 260 out of 942 immunologically relevant proteins in plasma in these individuals.

Here are the key results from the study:

Among the 260 infection-related proteins, the researchers found that 35 were associated with changes in brain areas susceptible to volume loss with infection.

They also identified proteins to be associated with cognitive decline and biomarkers of Alzheimer’s disease and neurodegeneration.

The researchers concluded:

Using data from multiple large cohort studies, our findings illustrate how a range of infections, namely influenza, herpes viruses, URTIs (upper respiratory tract infections), LRTIs (lower respiratory tract infections), skin and subcutaneous infections and a category of miscellaneous viral infections, are associated with increased regional brain atrophy and risk for future dementia.

Summary

This study is supported by other studies that have shown that certain infections or being vaccinated against infectious diseases are linked to an increased risk of dementia and/or Alzheimer’s disease.

Many of these infections can be prevented by vaccines — upper and lower respiratory tract infections are often caused by RSV, which can be prevented with the RSV vaccine. Of course, there are other vaccines for various serious infections like flu, shingles, and many others.

It is clear that preventing infectious diseases can reduce the risk of dementia. So, get vaccinated against the diseases that can result in serious infections.

Citations

Duggan MR, Peng Z, Sipilä PN, Lindbohm JV, Chen J, Lu Y, Davatzikos C, Erus G, Hohman TJ, Andrews SJ, Candia J, Tanaka T, Joynes CM, Alvarado CX, Nalls MA, Cordon J, Daya GN, An Y, Lewis A, Moghekar A, Palta P, Coresh J, Ferrucci L, Kivimäki M, Walker KA. Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nat Aging. 2024 Sep;4(9):1263-1278. doi: 10.1038/s43587-024-00682-4. Epub 2024 Aug 14. PMID: 39143319; PMCID: PMC11408246.

Michael Simpson

Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!