Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford
Jun
26
2010

Physical Exercise

essential

control

Physical-Exercise

Everywhere we turn, we hear information about the benefits of exercise. From building stronger bones and muscles to reducing the risk of diseases such as diabetes and heart disease, the effects of physical exercise on general health are certainly far-ranging. In fact, a growing body of research is demonstrating that physical exercise is good for your body as well as your brain. Recent examinations of the link between physical exercise and the central nervous system have shown positive effects on a wide range of brain health markers. So, in addition to the obvious reasons to exercise – such as maintaining a trim physique and a healthy heart – there is also the added benefit of keeping your brain healthy, which can lead to increases in cognition and memory. On a broad level, exercise is essential for maintaining good blood flow to the brain and increasing the brain’s consumption of oxygen and glucose. On a more specific level, exercise appears to have profound effects on specific molecular systems involved in the regulation of neuroplasticity. Together, these effects result in a well-preserved brain that is more adaptive to change.

The purpose of this chapter is to provide information about the benefits of physical exercise and to explore how this life practice may affect the way that individuals respond to HD. Exercise, especially for people with HD who experience significant brain loss as well as a variety of health-debilitating symptoms, is an excellent life practice because it proactively addresses health on a variety of fronts.

Exercise and Capillary Density^

In general, exercise improves the heart’s ability to pump blood and increases the natural ability of blood to carry oxygen to cells throughout the body. With exercise, blood circulation to the brain is thus increased and the brain receives more oxygen and glucose, both of which are crucial to brain function. The brain is the body’s most active organ and it requires the most energy. Although it accounts for only 2% of our body weight, it uses between 20% and 30% of the body’s energy. Despite this need for a large amount of energy, the brain can not store any oxygen or glucose. It is therefore necessary for the blood stream to deliver a constant supply of these essential substances, and it does this by circulating continuously through the brain. A person can feel a lack of oxygen after only a few seconds. When you stand up too quickly and become dizzy, this is an example of loss of blood flow to the brain that can be sensed. Diabetics who give themselves too much insulin can drop their blood sugar level and faint, and can die unless they quickly increase the level of glucose in the brain. Adequate blood circulation and the vast network of blood vessels that serve the brain and allow for blood flow are thus critical. The 400 miles of blood vessels in the human brain have a surface area of approximately 100 square feet. The health of these vessel walls is very important for proper brain function. In addition to delivering a constant supply of oxygen, glucose, and other important nutrients to the brain, blood flow to and from the brain also removes harmful toxins. So overall, having a proper functioning vascular (blood vessel) system is absolutely necessary for optimal brain health and functioning.

When blood flow to the brain is increased, the body responds by forming new blood vessels to bring the extra blood to nerve cells. This process, known as angiogenesis, is directly connected to neurogenesis, the process of making new nerve cells. It was initially believed that angiogenesis, much like neurogenesis, was limited to certain periods of development or in response to pathological insults. It has since been discovered that angiogenesis naturally occurs when physical activity is increased, and can be induced by exposure to a complex environment or exercise. Thus, the formation of new blood vessels is not restricted to developmental periods but extends into mature adulthood and beyond. For example, in the dentate gyrus, a brain structure that experiences a great amount of neurodegeneration on account of HD, new nerve cells are clustered close to blood vessels. These nerve cells can only grow and be healthy when there is enough blood flow to the brain. Researchers believe that decreased blood flow to the brain as a result of fewer blood vessels contributes to the decline in new cell production among older individuals. Moreover, exercise has been shown to increase angiogenesis and nerve cell proliferation throughout the brain in various animal models like mice and fruit flies.

It turns out that there is a good reason why exercise seems to “clear your head.” Your heart rate increases as you exercise, increasing blood flow to the brain, which enhances waste removal and provides much-needed oxygen and glucose. In a test, students had a one-minute blast of oxygen given to them immediately before being given a list of words to remember. On average, the students who took the oxygen remembered two to three more words from a list of 15 than those who did not. Students who took oxygen while playing the Tetris computer game on its most demanding level were also shown to play significantly better. Exercise can act very similarly to having a one minute blast of oxygen. If performed on a consistent basis, exercise has the effect of providing a dose of continuous oxygen to the brain, such that the cognitive boosts can be continually maintained as well. The increase in blood circulation because of exercise can induce the formation of new blood vessels that can, in turn, facilitate the creation of new nerve cells.

Exercise and Cognitive Maintenance^

Even people who do not have HD experience a moderate amount of neurodegeneration as part of the normal aging process. Here, the signals that nerve cells use to communicate with one another become less powerful and less efficient. This decreased ability for nerve cells to communicate makes it harder for the brain to adapt to outside influences and generate new nerve cells. The inability to create new nerve cells leads to losses in brain tissue and impaired functioning. Indeed, imaging studies in elderly humans have shown some noticeable atrophy in the brain. In people with HD, this atrophy is substantially magnified. One of the consequences of atrophy is that older adults typically perform more poorly than younger adults on a broad range of cognitive measures. (For more information on cognitive symptoms of HD, click here)

Despite such declines in cognitive and motor processes during the course of aging in people with HD, recent findings suggest that physical exercise can minimize some, but not all, kinds of cognitive decline. A recent study showed that older adults who exercised throughout life had less brain tissue loss and performed significantly better on cognitive tests than adults who exercised infrequently. Similarly, a study with twins done in Sweden found that the twin who exercised more was also more likely to score higher on a cognitive test. It is important to note that these tests show correlation and do not necessarily prove causation. In other words, just because people who exercise a lot show increased cognitive abilities, this does not necessarily mean that one causes the other. For example, people who exercise more may also have better eating habits such that improved nutrition leads to better cognitive scores. Nevertheless, as indicated by the numerous studies discussed below, the role of exercise in cognitive maintenance should not be discounted.

It turns out that the areas in the brain that are associated with mental decline due to aging are the same areas that are the most responsive to exercise. Researchers have found that people who exercise a lot have more gray matter and white matter in the brain, particularly in the frontal lobe, temporal lobe, and parietal lobe. The lobes of the brain are composed of gray matter and white matter. Gray matter is where all the nerve centers are located. White matter connects the gray matter together. (For more information about the brain and its structures, click here.) The amount of gray matter and white matter declines naturally, affecting the functioning of the lobes and contributing to a decline in cognitive functioning and processing ability.

It has been found that individuals with HD typically have a substantially reduced volume of gray matter and white matter in the brain, especially in the temporal lobe and the frontal lobe. This is significant, given the prominent roles that each of these lobes play in the cognitive processes. The frontal lobes of the brain have a lot to do with what people call higher-level cognition, where we synthesize information, and store data we’ve just acquired. If the frontal lobes are not functioning properly, then you can easily forget a phone number you just looked up or the name of a person you just met. The temporal lobes consolidate short-term memories and build them into long-term memories. Damage to temporal lobes can also result in altered personality and affective behavior. The parietal lobes allow us to construct a spatial coordinate system to represent the world around us. Damage to the parietal lobes can result in neglecting part of the body or space, which can impair many self-care skills such as dressing and washing. (For more information about the lobes of the brain, click here.) Deterioration of each of these lobes is associated with some sort of mental decline. Exercise appears to exert its effects partially by protecting against a loss of gray matter and white matter, thereby preserving the structure and function of the lobes in the brain. With the lobes able to function better, the onset and progression of various cognitive deficits are likely to be delayed.

The fact that some degree of neurodegeneration is part of the normal aging process means that a person with HD must deal with these changes in addition to disease-related loss. Preserving cognitive function and preventing mental decline is definitely an uphill battle and some amount of neurodegeneration is inevitable. But this does not mean that the situation is hopeless. Studies on exercise reveal that it may indeed play an influential role in slowing down cognitive decline. As the rest of this chapter reveals, exercise exerts numerous other beneficial effects throughout the body and is thus a wonderful practice to incorporate into the daily routine. Later in this chapter, we’ll give some suggestions for where to begin.

BDNF^

In addition to keeping the brain’s lobes healthier and more intact, physical exercise can act directly on the brain’s molecular machinery. There is increasing recognition that physical activity can help relieve the effects of deterioration of nerve cell function. Numerous scientific studies with animals have reported that voluntary exercise leads to an increase in production of Brain-Derived Neurotrophic Factor (BDNF). This is a kind of protein that aids in the growth and survival of nerve cells during development, and in the maintenance of adult nerve cells. Because BDNF has both neurotrophic and neuroprotective properties, it is able to significantly influence brain plasticity. (For more information on BDNF, click here.)

HD invariably leads to decreased levels of BDNF, leaving nerve cells more vulnerable and prone to injury or death. In people without HD who have the normal huntingtin protein, the huntingtin protein indirectly activates the promoter, or the “on” switch, of the gene that encodes BDNF. When this gene is turned on, it prompts nerve cells to make more BDNF. In people who have HD, mutant huntingtin indirectly inactivates the “on” switch so that BDNF can no longer be produced. In the absence of BDNF, the cell’s ability to survive is markedly decreased.

Currently, scientists are looking for ways to harness neurotrophic factors such as BDNF so they can be administered to patients. This treatment would theoretically improve the symptoms of people with neurological disorders because it would dramatically improve the health and survival of the person’s nerve cells. Animal studies and in vitro models both indicate that BDNF is capable of making damaged nerve cells regrow. Because of this capability, BDNF represents an exciting possibility for reversing brain disorders, such as HD. The fascinating part of BDNF is that the protein can naturally be increased through exercise. In one rat study, several days of voluntary wheel-running increased levels of BDNF. The changes in BDNF levels were found in nerve cells within days in both male and female rats and were sustained for several weeks after exercise.

In particular, running activity increases levels of BDNF in the lumbar spinal cord, cerebellum, and cortex, but not in the striatum. Since the main site of neurodegeneration in people with HD is the striatum, exercise alone will likely not be able to prevent many of the symptoms of the disease. However, exercise can help preserve cognitive function and promote the general health of the brain, as well as the general health of the body overall. Although exercise may not be able to promote neurogenesis (the growth of nerve cells) in the striatum, it may promote neurogenesis in other areas of the brain and body by increasing the vitality of nerve cells. These changes may be enough to delay the onset and progression of various HD symptoms.

Exercise and Stress Alleviation^

Exercise may also help the brain to better cope with stress. Stress leads to the release of various neurochemicals and stress hormones. (For more information on stress and its effects on the brain, click here.) Prolonged exposure to stress hormones is detrimental to the health and survival of nerve cells. Normal nerve cells are like miniature trees with a lot of branches. These “branches” are called dendrites. They are structures that connect one nerve cell to many other nerve cells. Stress hormones cause the branches of the dendrites to become shorter and less widespread, such that the affected nerve cell cannot connect to as many nerve cells. With fewer connections, it does not receive as much information as it should, and becomes more prone to injury or death. It is thought that this effect occurs mainly because stress hormones decrease the amount of BDNF in the brain, depriving nerve cells of neurotrophic factors necessary for growth and survival. Exercise directly counteracts this effect by increasing BDNF availability in the brain. As evidence, in a study in which two groups of rats were exposed to stressful stimuli, the effect of exposure to this stress was mediated by exercise. Rats that were able exercise before exposure to the stressful stimuli had normal amounts of BDNF in the brain, whereas rats that were not able to exercise had significantly decreased amounts of BDNF in the brain.

In addition to increasing BDNF availability, exercise also helps regulate the release of harmful stress hormones, so that they don’t flood into the nerve cells and wreak havoc. Researchers first became interested in exploring a possible link between exercise and stress after discovering that physically fit individuals have significantly lowered rates of anxiety and depression. Although popular theory states that exercise causes a rush of endorphins, there is very little evidence for this phenomena. Instead, researchers believe that a chemical known as norepinephrine plays a key role in helping the brain deal with stress more efficiently. During exercise, norephinephrine is released and goes on to directly increase heart rate, release energy from fat, and increase muscle readiness. Studies in animals since the late 1980′s have found that exercise increases concentrations of norepinephrine in regions of the brain involved in the body’s stress response. Although the exact mechanism is not known, increased norepinephrine in the brain is thought to decrease the release of other harmful stress chemicals. In fact, some antidepressants work by increasing brain concentrations of norepinephrine.

Many physiologists believe that exercise also enhances the body’s ability to respond to stress in a more general way. Biologically, exercise seems to give the body a chance to practice dealing with stress. It forces the body’s physiological systems, all of which are involved in the stress response, to communicate much more closely than usual; e.g. the cardiovascular system communicates with the renal system, which communicates with the muscular system. All are controlled by the central nervous system and sympathetic nervous system, which must also communicate with each other. This “workout” of the body’s communication system may be the true value of exercise; the more sedentary we get, the less efficient our bodies become in responding to stress.

Biological evolution of exercise^

The widespread effects of exercise should not be surprising considering that the human body evolved in an environment of regular physical activity. Biologically, it was part of survival. Physical capability was necessary for success at hunting, gathering food, and providing shelter and safety. What is now considered a form of exercise – walking – was originally a form of transportation.

Today, many people see physical movement as an optional part of their lifestyles. This type of thinking is unfortunate considering the integral role that exercise plays, not only in general health, but also numerous cellular and molecular cascades that protect the brain. Not surprisingly, a lack of exercise is linked to increased incidence of many diseases. Additionally, the ability to perform day-to-day activities declines: to walk without falling, to rise from a chair or get in and out of a car unaided, to carry a bag of groceries, to tie shoes, etc. Although human lifestyles have changed, and exercise is no longer a necessary part of our daily survival, our bodies still need exercise. We must consciously make an effort to incorporate some sort of physical activity into our daily life routine.

Exercise and HD^

During the progression of HD, a person will decline in health and be forced to lead a more sedentary lifestyle. Although the disease process can’t be altered, a routine exercise program can help to address many areas of decline, as well as increase strength, improve balance and posture, and allow the individual to feel more in control of his/her body. Aerobic activity, such as pedaling, jogging, or walking, may improve breathing, which in turn may help with breath control for talking and eating. Improvement in deep breathing will also help maintain the ability to cough effectively, which helps prevent choking and aspiration pneumonia. Regular exercise also makes it easier for people to clear secretions more efficiently when they do have colds or pneumonia. Growing evidence shows that physical exercise does not have to be strenuous or even require a major time commitment. It is most effective when done regularly, and in combination with a brain-healthy diet, mental activity, and social interaction.

Getting Started^

Physical activity is any bodily movement that burns calories, such as gardening, vacuuming, shoveling snow, walking to the store, climbing stairs, or playing ball with your grandchildren. As such, anyone can improve their physical fitness, regardless of age or physical condition. In fact, the greatest improvements are often seen among the frailest individuals who are nurtured through an exercise program. The easiest, safest, and most readily available physical activity for a person with HD is walking. It can be combined with a purposeful activity, such as walking a dog, pushing a person in a wheelchair, walking to the store to buy a newspaper or groceries, or picking up trash in the neighborhood.

Convincing people of the benefits of exercise is an essential first step. Many people with HD are worried about becoming a burden to their families. Explaining that exercise can help keep them healthy and make caregiving easier on their loved ones can be a strong selling point. But it is first important to consult with a physician before embarking on an exercise program. A health history and physical may reveal cardiac, musculoskeletal, or other problems that may impose restrictions on the type and intensity of exercise to be undertaken. If this is the case, request a referral to a physical therapist or cardiac-rehab specialist to work out a beginning regimen that is suitable for the individual. It may help to ask the person’s physician to reinforce his or her exercise recommendation by writing out a prescription that can be shown to the individual periodically. Such an instruction carries more weight than suggestions from a caregiver. The key to motivating people to persevere in any program of lifestyle change is social support. Fitness club membership lists are filled with names of people who rarely come to work out after an initial “honeymoon” period. Many home treadmills, exercise bikes, and other fad equipment are unused after this initial period. Exercise programs for persons with disabilities that are successful are all characterized by the presence of exercise “buddies” or program monitors that provide ongoing supervision and encouragement.

For further reading^

  1. “Advanced Stages of Huntington’s Disease Caregivers Handbook: Exercise and Fitness.” http://huntingtondisease.tripod.com/advancedstagesofhd/id8.html
    This is a Huntington’s Disease Handbook that has a chapter on exercise that discussed the importance of exercise and discusses sample exercise plans.
  2. Bloor, CM. (2005). “Angiogenesis during exercise and training.” Angiogenesis 8(3): 263-71.
    This technical article thoroughly examines the link between angiogenesis and physical activity.
  3. White, L. (2005). “Exercise and Cognitive Function.” The Lancet Neurology. 4(11): 690-691.
    This article explains the ways in which exercise can impact cognitive function.

-D. McGee, 4-30-06; recorded by B. Tatum, 8/21/12