According to studies done on humans, a greater lifetime exposure to microbial illnesses is linked to a slower decline in cognitive function as people age.

By intermittently giving mice the inflammation-causing bacterial toxin lipopolysaccharide, a recent animal study examined the effect of inflammation brought on by recurrent microbial infections on cognitive function.

The study discovered that early middle-aged mice with mild-to-moderate inflammation brought on by repeated lipopolysaccharide treatment had deficiencies in memory and learning.

These results in ageing mice imply that mild-to-moderate illness brought on by microbial infections may require more vigorous therapy than the existing standard of care, particularly in populations susceptible to cognitive impairment, such as the elderly.

The standard medical advise for those with mild to moderate infections is to obtain enough rest and drink more fluids. It’s interesting to note that a recent study in the journal Brain, Behaviour, and Immunity claims that repeated inflammation brought on by giving a bacterial toxin to middle-aged rats led to cognitive deficiencies. Along with these cognitive deficiencies, the hippocampus, a part of the brain important for learning and memory, experienced changes in the plasticity of its neurons.

Elderly people are more prone to microbial infections, which could exacerbate the decline in cognitive function in elderly people and result in dementia or moderate cognitive impairment.

The results of this study point to the possibility that older persons may require more intensive therapies in order to avoid these illnesses’ long-term consequences on cognitive function. It is crucial to remember that since this study used a mouse model, it is unknown whether the conclusions apply to people as well.

Brain aging contributed by inflammation

As a result of the biological changes brought on by brain ageing, a loss in several cognitive capacities is shown during the course of normal ageing. Similar to this, cognitive impairment seen in neurodegenerative diseases like Alzheimer’s disease is connected to pathological brain ageing.

According to studies, several variables, including inflammation brought on by microbial infections, may accelerate the aging of the brain. For instance, higher lifetime exposure to infectious agents is linked to worse cognitive function and a faster decline in cognitive function in older people.

Additionally, research using animal models has demonstrated that inflammation brought on by microbial exposure might affect cognitive function. Animals are injected with the toxin lipopolysaccharide (LPS), which is found in the outer membrane of gram-negative bacteria, to study the effects of inflammation brought on by microbial infections.

These investigations on animals have demonstrated that LPS injection can elevate cytokine levels in the brain, a family of inflammatory proteins, and result in abnormalities in cognitive function. Additionally, as people age, these negative effects of LPS become more obvious.

The majority of these studies have looked at how LPS affects brain and cognitive function when it is given continuously or in single doses. According to these research, even a single dose of LPS-induced inflammation can alter the brain permanently.

However, little study has been done on the effects of lifetime exposure to microbial illnesses on alterations in the brain and cognitive function. In genetically modified mouse models of Alzheimer’s disease, there is some indication that repeated injection of LPS can raise the risk of cognitive impairment.

EFfects of LPS-induced inflammation

In the current investigation, mice were given escalating dosages of LPS every 15 days for 2.5 months. Repeated injection of the same amount of LPS causes tolerance to develop, which includes the absence of an inflammatory reaction, according to prior studies.

The researchers worked around this problem by gradually increasing the LPS dose over the course of the five injections. The mice experienced mild illness after each LPS treatment, but they recovered within 15 days.

Two weeks after giving the last dosage of lipopolysaccharide, the researchers then tested the animals’ behaviour to see how well they could think. At 5–6 weeks after the last injection, the researchers also put the animals to death to look at how inflammation brought on by lipopolysaccharide affected the brain.

Saline-treated mice made comprised the control group. The mice were 10 months old when the study began, which corresponds to the transition from late adulthood to middle age.

The scientists discovered that mice given LPS injections displayed cognitive abnormalities in learning and memory retention of information acquired the day before.

Researchers observed alterations in the hippocampus in mice who received LPS injections on a sporadic basis. In Alzheimer’s disease, the hippocampus, which is important for memory and learning, exhibits the illness’s initial signs of degradation.

Interleukin-6 (IL-6) gene expression was upregulated in the hippocampus of LPS-treated mice as one of these modifications. This is in line with other research that found higher IL-6 levels following LPS treatment in cognition-related brain areas.

Additionally, the researchers discovered that giving LPS affected neuronal plasticity but not baseline signal transmission. Particularly, the LPS-treated animals displayed reduced long-term potentiation (LTP) between neurons in the hippocampus.

Linking flu frequency to dementia risk

Dr. Elizabeth Engler-Chiurazzi, a behavioral neuroscientist at Tulane University and co-author of the study, said the conclusions have significant ramifications for human brain health and disease.

“At the moment, staying in bed, getting lots of rest, drinking soup, and allowing your body to do its work of eradicating the infection is the standard of care for the common cold or the flu virus. According to my knowledge, this advice is offered to the entire population and is given regardless of the likelihood that dementia will develop in the future.

Dr. Elizabeth Engler-Chiurazzi stated, “Our results may be the first in a series of studies that could indicate that treatment for the common cold or other sources of intermittent infection among patients at high risk for cognitive decline/dementia may need to be more aggressive than the standard recommendations of rest and fluids.”

According to these findings, a history of more “flu-like” episodes may be a risk factor for cognitive problems in later life. According to Dr. Engler-Chiurazzi, some research conducted in people have started to investigate this connection. The results are consistent with our mouse observations.

It’s too soon to say for sure.

Dr. Engler-Chiurazzi issued a warning, noting that it’s possible that these findings won’t apply to people.

Although there are significant species differences in how these systems react, the immune system composition of mice and people is similar, according to the researcher. However, more research is required to determine how well these findings are replicated in human populations.

The mechanisms behind the cognitive losses following repeated LPS treatment will also be looked at by the authors.

Dr. Engler-Chiurazzi stated, “An immediate next step for our group is to repeat these studies and determine the extent to which common brain consequences seen in dementia, such as a leaky blood-brain barrier or activation of brain immune cells (microglia), are observed after repeated intermittent exposure to sickness-like inflammation in the body.”

Dr. Engler-Chiurazzi also mentioned that they have not looked at how viral infections affect cognitive function but are now doing so using an animal model.

REFERENES:

• https://www.medicalnewstoday.com/articles/frequent-colds-and-flu-may-increase-dementia-risk
• https://www.news-medical.net/news/20230404/Getting-sick-often-may-increase-the-risk-of-dementia.aspx
• https://news.tulane.edu/pr/does-getting-cold-often-increase-your-risk-dementia-new-study-finds-link

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