Cognitive decline: What causes and slow it down.

Cognitive decline: What causes and slow it down.

Age-related cognitive and memory deterioration is a universal phenomenon, however the specific causes are yet unknown to science. While some lifestyle choices can prevent cognitive decline, age-related illnesses like dementia speed it up.

One recent study using mice models may now have identified the primary mechanism underlying the cognitive impairment brought on by typical aging.

Another recent study, this one using mice, raised the possibility that social connection, cognitive training, and physical activity could halt the ageing process and prevent cognitive deterioration.

As we become older, our cognitive abilities—the brain processes that enable thinking, learning, memory, awareness of one’s environment, and judgment—change. Our capacity to process information and make decisions swiftly decreases as our brain’s nerve cells and synapses age.

Most people begin to notice a steady deterioration at around age 50. However, advances in cumulative knowledge continue far into old life together with this minor decline in processing speed and working memory.

But why are the changes happening? According to a recent study conducted on mice, changes in a brain protein may limit synaptic plasticity, the capacity of nerve cells to change the strength of their connections, which impairs memory. This research is published in Science Signalling.

We may be able to prevent age-related cognitive loss, according to a different study conducted on mice. In this study, which was published in the journal Ageing, researchers hypothesise that social interaction, mental exercise, and physical activity all work to activate an enzyme that enhances the functionality of nerve cells and synapses, enhancing cognitive performance.

What leads to cognitive ageing?

The first study focused on CaM kinase II (CaMKII), an enzyme that is involved in synaptic plasticity and the transmission of nerve impulses across synapses, among other functions.

They simulated the cognitive effects of typical ageing in mice by changing this brain protein.

Nitric oxide (NO), according to earlier research by the same authors, may influence CaMKII’s function. This work expanded on previous investigation and discovered that CaMKII is modified via a procedure termed S-nitrosylation, which depends on NO.

Memory and learning skills are hampered if CaMKII’s nitrosylation is diminished, which occurs with natural ageing.

Prof. Ulli Bayer, of the University of Colorado Anschutz School of Medicine and the study author, outlined the potential causes of this.

He explained to us that the diminished nitrosylation of CaMKII results in a decrease in its synaptic localisation, which appears to impede its synaptic activities.

Simply put, a decrease in NO decreases the transmission of nerve impulses through the synapses between nerve cells, which may contribute to cognitive deterioration.

Cognitive decline and way of life

The benefits of a healthy lifestyle on brain health have long been recognised by researchers. According to a 2015 study, exercise, intermittent fasting, and critical thinking are crucial for maintaining good brain function over the course of a person’s lifetime.

In people with normal cognition, a healthy lifestyle is linked to a slower rate of memory impairment, according to another extensive study.

Social connection, physical activity, and cognitive training are all positive experiences that are beneficial to cognitive health. The precise mechanism by which these lifestyle factors work is unknown.

A mechanism that could explain how these satisfying events improve your brain health has now been discovered by the Ageing study, which was carried out in mice.

For ten weeks, the researchers kept adult and senior mice in an enhanced environment. They were housed in huge cages with bedding, a cardboard tube, a running wheel, many plastic toys (tunnels, platforms, see-saws), and a metal ladder in groups of eight to ten mice each. Twice per week, the toys were rearranged, and once per week, new toys were added.

The only items in the control group’s regular cages, which were housed in groups of two to four mice each, were bedding and a cardboard tube.

The researchers tested the cognitive abilities of both groups once every week using land and water mazes. These were put to the test:

  • working memory for space the capacity to temporarily maintain spatial information engaged in working memory.
  • cognitive adaptability, or the capacity to change with the environment
  • Long-term recall of task-related spatial, factual, and contextual elements is known as spatial reference memory.

How enrichment keeps cognitive ability intact?

Comparing mice in the usual environment to those in the enriched environment, the mice in the enhanced environment performed better on every behavioural task. The elder mice showed a particularly noticeable improvement.

Our study provides a potential mechanistic basis for the effects of enrichment — this removes the ‘wooliness’ associated with such enrichment studies and puts them on a more rigorous scientific basis,” said Prof. Bruno Frenguelli, corresponding author and a professor of neuroscience at the University of Warwick in the United Kingdom.

In mice with a mutation in the enzyme MSK1, which is involved in neural growth and synaptic plasticity, the researchers did not observe any advantages.

They came to the conclusion that MSK1 is necessary for enrichment to fully improve cognition, synaptic plasticity, and gene expression.

The following is how Prof. Frenguelli explained it to us:

MSK1 is an enzyme that controls gene expression, or more specifically, it stimulates the activation of a variety of genes. We believe that MSK1 influences cognition by turning on a number of these genes because they have been linked to various aspects of learning and memory.

Exercise, networking, and ongoing learning

“Although our mechanistic experiments were conducted in mice, earlier research has revealed that ageing reduces CaMKII’s nitrosylation in both mice and humans. Pharmacological therapies should be able to boost CaMKII’s nitrosylation and so reduce the cognitive losses related to normal ageing, according to Dr. Bayer.

While there are currently no such treatments, research is being done, as Dr. Bayer stated: “This needs further research/development, but there are actually candidate approaches — such as inhibitors of GSNOR, an enzyme that limits nitric oxide bioavailability, and that is higher expressed with aging.”

The second study, however, suggests that we might not have to wait for pharmacological treatments to stop cognitive ageing. Prof. Frenguelli provided an explanation of why lifestyle enrichment should be effective in both humans and mice.

A key brain growth factor (BDNF), which activates MSK1, has been implicated in both rodents and humans as being important for these benefits,” he said.

By identifying key molecules involved in this process, this offers opportunities to explore and exploit these molecules as drug targets,” the author continued.

And he added that you can never be too old to reap the benefits of physical activity, interpersonal contact, and mental stimulation: “Our recent findings show that these benefits occur even in very old mice (equivalent to 70s in humans), meaning that it’s never too late to offer and engage in such enrichment activities to elderly people.”

How do medical professionals spot cognitive decline?

If you’re unsure if you’re exhibiting usual ageing symptoms or cognitive decline indications, a doctor can help. For a quick self-screening exam to look for signs of cognitive deterioration, they might provide you.

Other screening exams, such as the Self-Administered Gerocognitive Examination (SAGE),

You can use a variety of screen tests to look for indicators of cognitive impairment. These exams typically last between three and fifteen minutes. They consist of:

  • Self-Administered Gerocognitive Examination (SAGE)
  • AD8 Dementia Screening Interview
  • Quick Dementia Rating System (QDRS)
  • Mini-Cog

One of the most popular screening exams is SAGE. The test is available for download online, and you can take it offline. You might even finish it off at a doctor’s office.

SAGE is unique from the other tests because it is a little bit more complicated. According to a 2022 study, SAGE identified cognitive impairment in MCI patients six months earlier than the MMSE, another popular test. A review from 2021 found that SAGE delivers the right answer 79% of the time.

Please take note that these brief tests alone cannot identify cognitive impairment or dementia. A doctor may need to conduct a more complete evaluation if your score starts to fall.


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