Longevity Briefs: Avoiding Infections Might Keep Your Brain Healthy

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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.

The problem:

Mounting evidence shows that certain infectious diseases are correlated with an increased risk of dementia. However, since people with dementia appear to have weakened immune systems, it isn’t clear whether infections are a cause or a consequence of the disease or, as is often the case, a bit of both. In this study, researchers analysed proteins in the blood in an attempt to get a better picture of how infections might promote cognitive decline and dementia.

The discovery:

The study analysed data from a total of 982 cognitively normal people aged 65.4 on average. This data came from a long-term study (the Baltimore Longitudinal Study of Ageing or BLSA) in which diagnosed infectious diseases were recorded. These were mostly infections carrying some risk of severe complications such as influenza, tuberculosis and hepatitis. They found that when compared to participants with no history of any of these infectious diseases, participants who had been diagnosed with influenza, herpes, lower or upper respiratory tract infections, skin infections or miscellaneous viral infections had a statistically significant reduction in volume in certain brain regions.

Annual changes in brain volume in different brain regions for different infectious diseases, compared to people with no history of infection. Pink squares represent statistically significant reductions. HHV: human herpes virus; URTI; upper respiratory tract infection; LRTI: lower respiratory tract infection.
*Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline*

The researchers then turned to two much larger samples including nearly 500,000 people from the UK Biobank and 273,000 people from a Finnish study. They found that all of the infections that were associated with reduced brain volume in the BLSA data were also associated with a significant increase in all-cause dementia risk, with the exception of miscellaneous viral infections in the Finnish study.

The researchers then went back to the BLSA study and analysed the proteins in the blood of 1,184 participants. They found that a history of infections was associated with changes in expression of 260 proteins relevant to immune function and with potential implications for dementia risk. Of those 260 proteins, 32 were also associated with brain volume changes and/or cognitive decline. Some proteins were protective and were reduced in people with an infection history, while others were associated with reduced brain volume and dementia biomarkers. For example, prior influenza infection was associated with lower levels of MME, an enzyme that degrades amyloid beta (a key hallmark of Alzheimer’s) as well as changes in expression of apolipoprotein E (APOE), of which the APOE4 variant is strongly associated with dementia.

The implications:

This study suggests that certain infections are associated with changes in levels of proteins linked to brain atrophy and dementia risk, and explores some of the possible mechanisms for this. These are worthy of further study, as they offer a potential means for earlier detection of dementia and perhaps even prevention or treatment. In the meantime, there are good reasons to suspect we can all decrease our risk of cognitive decline by limiting our exposure to infectious agents, getting vaccinated and treating infections swiftly.