Cognitive decline: Mouse studies suggest cause, preventive action

Evan Walker
Evan Walker TheMediTary.Com |
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Studies in mice go some way toward explaining why cognitive decline occurs later in life, and why some activities may help stave it off. Image credit: Thanasis Zovoilis/Getty Images.
  • Everyone experiences some decline in their thinking and memory skills as they age, but scientists do not yet know exactly why.
  • Age-related syndromes, such as dementia, accelerate the rate of cognitive decline, while some lifestyle factors can slow it.
  • One recent study, conducted on mouse models, may now have uncovered the central mechanism behind cognitive decline associated with normal aging.
  • Another recent study, also in mice, has suggested how social interaction, cognitive training, and physical exercise may slow cognitive decline as we age.

Cognition — the mental process of thinking, learning, remembering, being aware of surroundings, and using judgment — changes as we age.

As nerve cells and synapses in the brain alter over time, our ability to quickly process information and make decisions declines.

Most people notice a gradual decline starting at around the age of 50. However, this slight drop in processing speed and working memory is generally accompanied by improvements in cumulative knowledge well into old age.

But what causes the changes? A new study, in mice, suggests that alterations in a brain protein may impair Health">synaptic plasticity — the ability of nerve cells to modify the strength of their connections — leading to memory decline. This study appears in Science Signaling.

Another study, again in mice, suggests that we can help delay age-related cognitive decline. In this study, published in Aging, scientists suggest how social interaction, cognitive training, and physical exercise activate an enzyme that improves the functioning of nerve cells and synapses, resulting in enhanced cognitive performance.

Researchers have long known that a healthy lifestyle can boost brain health. One 2015 paper suggests that exercise, intermittent fasting, and critical thinking are essential for optimal brain health throughout life.

Another large-scale study found that a healthy lifestyle is associated with a slower rate of memory decline in adults with normal cognition.

Positive experiences, such as social interaction, physical exercise, and cognitive training are also good for cognitive health. What is not known is how exactly these lifestyle factors have their effect.

Now, the Aging study, conducted in mice, has found a mechanism that might explain how these positive experiences benefit your cognitive health.

The researchers put adult and elderly mice into an enriched environment for 10 weeks. They were kept in groups of eigh to 10 mice, in large cages with bedding, a cardboard tube, a running wheel, several plastic toys (tunnels, platforms, see-saws), and a metal ladder. The toys were moved around twice a week, and new toys introduced once a week.

The control group was kept in standard cages, in groups of two to four mice, with only bedding and a cardboard tube.

Once a week, the researchers used land and water mazes to test both groups’ cognitive function. They tested the following:

Mice that had been kept in the enriched environment had improved performance on all of the behavioral tasks compared with those in the normal environment. This improvement was particularly marked in the older mice.

“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 corresponding author Prof. Bruno Frenguelli, a professor of neuroscience in the School of Life Sciences at the University of Warwick, United Kingdom.

The researchers did not see the benefits in mice with a mutation in MSK1 — an enzyme involved in neuronal proliferation and synaptic plasticity.

They concluded that MSK1 is required for the full benefit of enrichment on cognitive abilities, synaptic plasticity, and gene expression.

Prof. Frenguelli told us how it works:

“MSK1 is an enzyme that, when activated, regulates gene expression — that is, it promotes the turning on of a wide range of genes. A number of these genes have been implicated in various forms of learning and memory, so we think that MSK1 exerts its beneficial effects on cognition via the switching on of these genes.”

“While our mechanistic studies are done in mice, previous studies have shown that aging causes a reduction of nitrosylation of CaMKII in both mice and humans. […] It should be possible to use pharmacological treatments that will increase the nitrosylation of CaMKII and thereby alleviate the cognitive deficits associated with normal aging,” Dr. Bayer told MNT.

Although such treatments are not yet available, research is underway, as Dr. Bayer explained: “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.”

But, the second study shows, we may not need to wait for pharmacological treatments to delay cognitive decline. Prof. Frenguelli explained why lifestyle enrichment should work in people as well as in 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 noted.

“[By] identifying key molecules involved in this process, this offers opportunities to explore and exploit these molecules as drug targets,” he added.

And, he advised, you are never too old to benefit from exercise, social interactions, and cognitive 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.”

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