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An active lifestyle may reduce Alzheimer’s risk

exercise
  • Physical activity has been shown to lessen the risk of Alzheimer’s disease and all-cause dementia, as well as slow cognitive loss as people age.
  • Increased inflammation in the brain is linked to aging and neurodegenerative diseases like Alzheimer’s disease.
  • Physical activity has been proven in animal experiments to improve cognition by lowering the activation of microglial cells, the brain’s primary immune cells.
  • According to a new study including older people, reduced microglial activation may help promote the protective effects of physical activity on cognitive functioning.

With age, certain cognitive functions, such as memory and attention, deteriorate. However, some people develop dementia, which is characterized by a significant loss of cognitive functions that impairs daily functioning.

Individuals who exercise regularly had a lower risk of Alzheimer’s disease and all-cause dementia, according to studies. Physical activity can also help to slow the onset of cognitive deterioration.

The processes by which physical activity delivers these cognitive benefits in humans are not entirely understood by scientists.

Reduced inflammation in the brain may mediate the cognitive benefits of physical activity, according to a recent study headed by researchers at the University of California, San Francisco (UCSF).

The researchers discovered that physical activity was linked to lower activation of microglia, the brain’s primary immune cells.

“Many studies suggest that physical activity is related to better brain and cognitive health (e.g., estimates indicate that inactivity alone contributes for 13 percent of Alzheimer’s disease cases worldwide),” research co-author Dr. Kaitlin Casaletto, a professor at UCSF, told Medical News Today. Despite this, scientists still don’t fully comprehend the mechanisms that link physical activity to cognitive in humans. Our research is the first to suggest that microglial activation (also known as “brain inflammation”) could be a significant factor.”

The findings were published in the Journal of Neuroscience.

Microglia and physical exercise

Neurons and glial cells are the two main cell types in the neurological system. Glial cells guard and maintain neurons, whereas neurons are principally involved in conveying electrical and chemical impulses. Glial cells have recently been shown to be able to alter signal transmission between neurons.

Glial cells in the brain may mediate the favorable effects of physical activity on cognitive performance, according to animal research. Physical exercise has been shown to affect the activity of microglia, a kind of glial cell.

Microglia are immune cells in the brain that become activated in the event of an infection or neuron injury.

Microglia activation can help the immune system produce an inflammatory response in response to an infection. However, an abnormal increase in microglia activity can harm neurons.

Low-grade chronic inflammation in the brain is a hallmark of aging and neurodegenerative diseases like Alzheimer’s disease. Furthermore, studies have revealed that these disorders are associated with an aberrant increase in the number of activated microglia in the brain.

Physical activity in animals lowers the activation of microglia and other inflammatory markers in the brain, according to scientists.

Synapses, which are specialized contact areas via which neurons connect with one another, can also be influenced by microglia. Microglia are involved in the development and dissolution of synapses.

They can also influence signal transmission between neurons by modulating the strength of these synapses.

The cognitive benefits of physical activity have been linked to improvements in synaptic health or integrity in animal studies. Microglia may also mediate the effects of physical activity on synaptic integrity and cognitive function, according to these findings.

The purpose of this study was to see if there was a link between physical exercise and microglial activation in elderly people. The study calculated the extent to which changes in microglial activity may support the effects of physical exercise, given the link between physical activity and improvements in cognitive performance and synaptic health.

Physical activity was linked to lower microglial activation in elderly individuals, just as it was in animals. Furthermore, the findings show that decreased microglial activation may be one of the brain routes by which physical activity protects people from cognitive decline, particularly in Alzheimer’s disease.

Measuring physical activity

The participants in this study were 167 people who had died and were part of the Rush Memory and Aging Project (MAP). The Rush Memory Assessment Program (MAP) is a long-term study aimed at identifying risk factors for Alzheimer’s disease.

The Rush MAP covers older persons without dementia at the time of enrollment and includes annual dementia risk factor assessments. The project participants agreed to give their brains and other organs for post-mortem examination.

The participants in this study were on average 87 years old at the time of the first physical activity test and 90 years old when they died.

The researchers used an actigraph wearable sensor to measure daily physical activity. Actigraphy tracks periods of motor activity and rest over several days to offer an objective measure of physical activity.

The researchers in this study did continuous actigraphy examinations for up to ten days. They also tested the subjects’ cognitive performance and their ability to do various motor tasks on a yearly basis.

The researchers studied the brain tissue of the subjects after they died to identify the quantity of activated microglia in four brain areas. They also looked at synaptic health proteins as well as brain indicators for Alzheimer’s disease, Lewy body dementia, stroke (infarcts), and other disorders.

Microglial activation and physical activity

When all four brain regions were analyzed together, the researchers discovered that higher levels of physical activity as measured by actigraphy were associated with a lower proportion of activated microglia.

Factors include impaired motor function and cognitive impairment could impede the participants’ capacity to engage in physical activity.

As a result, the researchers accounted for age, gender, motor performance, and cognitive function in their analyses. They discovered that these variables had no effect on the relationship between the fraction of activated microglia and physical activity.

The researchers next looked at this link in different parts of the brain. Only in two brain regions, the ventromedial caudate and the inferior temporal gyrus, did the link between increased physical activity and lower microglial activation approach statistical significance.

Furthermore, in people with greater brain diseases in these two brain regions, the link between physical exercise and lower microglial activation was stronger.

Microinfarcts (or mini-strokes) and Alzheimer’s disease-related pathologies were discovered in the ventromedial caudate and inferior temporal gyrus, respectively.

To put it another way, people with greater levels of brain diseases who frequently engaged in physical exercise had lower microglial activation than people with similar levels of brain pathologies but lower levels of physical activity.

These findings show that physical activity’s effects on microglial activation were limited to certain brain areas. These findings are in line with previous research that shows microinfarcts and Alzheimer’s disease-related brain diseases are more widespread in the two brain regions.

Association with cognition and synaptic integrity

The researchers then looked at the link between microglial activation and clinically relevant dementia markers, such as cognition and synaptic integrity.

Microglial activation in the inferior temporal gyrus, but not the ventromedial caudate, was linked to lower levels of synaptic health indicators and a deterioration in cognitive function.

The researchers then looked into whether reduced microglial activation caused by physical activity could benefit cognition and synaptic integrity.

The researchers calculated that the decrease in the number of activated microglia in the inferior temporal gyrus contributed to approximately 30% of the effects of physical activity on cognition and synaptic markers using a statistical method called mediation analysis.

More than 40% of the effects of physical activity on cognition and synaptic health were mediated by changes in microglial activation in the inferior temporal gyrus in those with greater levels of Alzheimer’s disease-related brain disorders.

Changes in microglial activity, on the other hand, only accounted for 10% of the effects of physical activity in people with less Alzheimer’s disease-related disorders.

Dr. Tristan Qingyun Li, commenting on the relevance of these results, said:

”This current work by Casaletto et al. is uniquely significant in that it provides the first evidence in humans to show that changes in microglial activation may be the mechanism bridging the beneficial effects of physical activity and healthier brain function. Furthermore, it points to a specific brain region, namely inferior temporal gyrus, that might be the most relevant for future microglia-based interventions.”

Dr. Li, who teaches at Washington University School of Medicine, was not engaged in the research.

Study strengths and limitations

The use of actigraphy, which enables an objective measurement of physical activity levels, was one of the study’s merits. This is in contrast to previous research that frequently use self-reports to assess physical activity levels, which are prone to biases and mistakes.

This is the first study in humans to show that physical activity can improve cognitive function by lowering microglial activation.

The study, according to Dr. Casaletto, had a few flaws. She said, “A major limitation of this work is the observational design. We cannot determine the directionality of effects, and it is likely that at least some of the relationship between physical activity and brain inflammation is bidirectional (i.e., brain inflammation leading to reductions in physical activity).”

In future investigations, Dr. Casaletto’s study group plans to solve this deficiency, according to her. She said, “We have a physical activity intervention study ongoing in which we hope to capture complementary markers of in-vivo inflammatory markers to help support causality of effects.”

Among other limitations, Dr. Casaletto noted, “We captured physical activity and cognition in life but brain inflammation and pathology at death. These are likely dynamic processes, and understanding the temporal link between lifestyle behaviors and biological changes is needed.”

Finally, Dr. Casaletto mentioned that the majority of the study participants were Caucasian and from Northeastern Illinois. As a result, the researchers are unsure if their findings can be applied to a diverse population.

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