Photo from PIxabay
(Click here to listen to an audio version of this blog …. Exercise and the brain )
Cause and effect are often tricky features of observational or epidemiological studies. For example, the often replicated and extremely well documented observation that individuals who exercise regularly are less likely to develop Alzheimer’s disease or other forms of aging dementia could be interpreted to mean that regular exercise does something to the brain that makes it resistant to the physiological and anatomical changes that lead to declines in cognitive function. This seems like a logical interpretation, and in 2017, a review article in the journal Brain Science did, indeed, conclude that physical activity does decrease the effects of cognitive decline in old age.
These same observations, though, that people who exercise don’t develop dementia as frequently as people who do not exercise, could, with equal logic, be turned around and present a very different “cause-and-effect” system. This new way of looking at the data would suggest that individuals who have even the earliest stages of brain deterioration that could lead to dementia might tend to be sedentary and not be part of a cohort that is physically active and out running or biking or working out in a gym!
So this is a very important question: Is physical activity and exercise a counterforce against dementia, or is it simply an indication that the roots of dementia are not present? Are there any molecular messengers that interconnect an exercising muscle to neurons in the brain? If so, what “messages” do these connectors convey?
Iris carrying water from the river Styx to the gods. Public Domain
In 2012, researchers at Harvard Medical School identified a new hormone that was synthesized by exercising muscle fibers. This hormone was named “irisin” after the Greek messenger god, Iris. Irisin targeted fat tissue and changed fat cells from their regular “white fat” metabolic state into the more vascular, mitochondrial rich “brown fat.” Brown fat has been shown to generate metabolic heat more rapidly than white fat and also improve both fat and sugar metabolism in physically active individuals.
Another finding about irisin, though, was even more momentous. Irisin was found to be able to cross the blood/brain barrier. Could it be one of the metabolic connections between exercising muscles and the brain?
In 2016, a paper published in the journal Neuroimage demonstrated that running increased the number of neurons in the dentate gyrus of the hippocampus (a part of the brain that is involved in memory and learning). Researchers at the National Institute of Health (NIH) found that exercise in both mice and humans stimulated the synthesis of new neurons in this area of the hippocampus and also facilitated their formation of synapses with other new and also existing neurons. The authors of this paper suspected that irisin might be the messenger that caused these neuron changes in the hippocampus.
H. V. Carter (from H. Gray) . Wikimedia Commons
In 2021, a paper published in Nature Metabolism described a series of exercise experiments conducted on a strain of mice that were bred to not be able to synthesize irisin. A control group of mice (that were able to synthesize irisin) were put into an exercise regime and increased neuron synthesis in the hippocampus and also increased memory and learning abilities were observed. When the irisin-less strain of mice were subjected to the same exercise program, however, no hippocampal neuron synthesis was observed and there was no improvement in memory or learning. These irisin-less mice were then given drugs to stimulate irisin’s synthesis, and the exercise programs stimulated hippocampal neuron synthesis and increased their ability the learn and remember.
Irisin, then, seems to link exercising muscle and the neurons of the brain!
Photo by J. A. Beal. Wikimedia Commons
Examining human brains at autopsy, irisin was found in all normal brains. It was absent, though, in the brains of individuals who had Alzheimer’s disease. This observation is a bit mysterious. Was irisin not being synthesized normally in patients with Alzheimer’s, or was it being broken down in the altered and intensely inflammatory environment of the Alzheimer brain? The role of irisin in Alzheimer’s patients needs to be studied more closely.
Another possible mechanism by which exercise could directly improve the overall health of the brain is via impacts on the cardiovascular system. Does blood flow to the brain improve when one exercises?
A study published earlier this year in the Journal of Alzheimer’s Disease looked at the physical health of the principal blood vessel that takes arterial blood to the brain: the carotid artery. Forty-eight patients with mild cognitive impairment participated in a year of prescribed exercise. At the end of the year the stiffness of each patient’s carotid artery (an indication of atherosclerotic disease) was measured as was the efficiency of their cerebral blood flow. Comparing pre-exercise data to post-exercise data clearly showed that exercise decreased carotid artery stiffness and increase the quality of cerebral blood prefusion. At the end of the year of study, though, there was no change in cognitive states of the patients.
Dementia affects between five and eight percent of the global population. In the United States alone, 14% of people over 71 years of age have some form of dementia, and Alzheimer’s disease, the most common type of dementia, affects 5.7 million people. In 2021, it estimated that the cost of Alzheimer’s disease in the United States will be $355 billion. By 2030, it is estimated ( by the Partnership to Fight Chronic Disease) that this cost will skyrocket to $7.7 trillion ($3.2 trillion in direct heath costs and $4.5 trillion in unpaid care giving costs). Research into irisin and other possible metabolic modulators of the normal brain generates critical data that can help medical sciences counter this epidemic of dementia.
Very difficult crossword puzzle! Pixabay.
In 2018 almost $2 billion was spent on mind games and puzzles that were marketed as preventatives against the loss of cognitive acuity. The World Health Organization (WHO) advises our aging population to stop spending money on these games and programs: none of them have been shown to be at all effective in preventing, slowing or reversing any form of dementia. Instead, WHO says that everyone should get out and exercise! A minimum of 150 minutes of exercise a week would do more to stave off this epidemic of dementia than any game or collection of cross-wood puzzles!
(Next week: exercise as a way to battle cancer!)