Low Skeletal Muscle Mass Is Associated with Cognitive Decline as Individuals Age

Skeletal Mass

A recent research project has confirmed that a relationship exists between lack of physical exercise and the onset of dementia in aging individuals. The researchers pinpointed four pathophysiological mechanisms that connect low muscle mass and  cognitive decline. These pathophysiological mechanisms are systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function.

A report on the research, which appeared in The Journals of Gerontology, Series A, in October, provided a detailed explanation of why low skeletal muscle in aging individuals is associated with an impairment of their cognitive activity.

Sarcopenia – the natural loss of muscle tissue as part of the aging process – was found to be three times more prevalent in older individuals with dementia than those without the disease, in a community-living environment.

“We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity,” the authors wrote. “Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood–brain barrier.”

Myokines are proteins that are produced by activity of the muscle tissues. When that activity diminishes or ceases as people age,  the research found, it has the potential to impair the flow of insulin “across the blood-brain barrier.” Previous studies have demonstrated a direct link between insulin and cognitive function.

The researchers not only say that the lack of physical activity can contribute to cognitive decline, but also — and more encouraging — that engaging in physical activity can help stave it off.

“Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence,” the study explained. “A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.”

Yet despite evidence that the four bodily mechanisms are at the root of the relationship between low muscle activity and dementia, the exact causal nature of that link is cloudy.

“Whether these mechanisms drive the pathophysiology of cognitive impairment and therewith explain the association of sarcopenia and cognitive impairment, or whether these mechanisms are indirect links between sarcopenia and cognitive impairment, is debatable,” the report stated. “It remains unclear if these mechanisms are directly or indirectly caused by skeletal muscle mass loss or if a bidirectional relationship exists. The underlying mechanisms of protein metabolism and mitochondrial function because of low skeletal muscle mass needs further exploration in relation to cognition.”

The researchers said that by identifying the four underlying mechanisms related to dementia, they hoped “novel treatments” may evolve, as well as “targeted interventions” to restore muscle mass, reversing the progression of sarcopenia and, possibly, improve cognitive functioning.


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