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Stress and Huntington's Disease






Because of the hustle and bustle of everyday life, everyone is familiar with the concept of stress. We can easily recognize when we are feeling stressed because of the various physical sensations that arise from it. Some of the symptoms of stress include shortness of breath, heart palpitations, headache, and fatigue. However, stress can also have much more significant and long-lasting effects. Throughout the last few decades, scientists have investigated the connection between stress and disease. Although stress does not play a direct role in the onset and development of Huntington´s disease (HD) itself, it does have an influence on the course of the disease. The leading causes of death in people with HD are not due to HD directly, but result from complications such as pneumonia and heart disease, both of which are known to be mediated by stress. (For more information on Complications of HD, click here.) It is important to know that stress can lead to complications and the worsening of symptoms in people with HD.

How do our bodies deal with stress? How can stress be harmful over the long term? How can we combat stress? This chapter discusses the answers to each of these questions.

A Brief Overview of the Stress Response^

Our body’s response mechanisms are well adapted for dealing with short-term physical emergencies. If a lion suddenly pops out in front of us, our bodies undergo a series of physiological changes that prepare us to either stay and fight the lion or run away from it – what is commonly known as the “fight or flight response.” These life-threatening situations are exactly why these changes, collectively called the stress response, evolved in humans and other animals. When we sit around and worry about stressful things such as deadlines, taxes, or family problems, we turn on the same physiological responses, which can be a problem when provoked all the time. Stress causes a variety of physical symptoms primarily because we constantly activate a physiological system that was only designed for responding to emergencies.

To understand how stress affects the body, it is important to understand the concept of homeostasis. In order for the body to function at its best, it must maintain a constant internal environment. Homeostasis is the process that maintains all biological processes within a certain range. Numerous physiological measures in the body such as oxygen levels, acidity, temperature, etc. must be kept at certain levels in order for the body to function properly. A stressor is anything that throws the body out of this balance by changing one or more of its essential factors from an optimal level to a non-optimal level. Stressors can include injury, illness, exposure to extreme heat or cold, or mental/emotional trauma. The stress response is the body´s attempt to restore homeostasis, or bring things back to normal.

In order to restore homeostasis, the body typically requires energy. Energy is normally stored in various parts of the body until it is needed. The stress response begins when the different sources of energy are quickly brought out of storage and no further energy is stored. Glucose and simple forms of proteins and fats come streaming out of the fat cells and liver into the bloodstream so that they can be taken up by the muscles and other organs that need them. Heart rate, blood pressure, and breathing rate also increase so that nutrients and oxygen can be transported to the most important organs at a greater rate. In addition, under the influence of a stressor, the body halts many non-essential long-term processes. If we need to run away from a lion, we don´t have time to wait for the energy that comes out of the slow digestion process – our last meal can wait to be digested until we are safe from that lion! Similarly, long-term building projects such as growth and reproductive processes are also inhibited during stress because these processes aren´t necessary for immediate survival. Even the immune system is inhibited because when dealing with a stressor, it simply does not make sense for our bodies to fight infections and waste energy when the lion that is chasing us may kill us in a few seconds. Once again, we can delay fighting infections until after we escape that lion!

The stress response works extremely well when there is an immediate physical stressor, such as a dangerous predator, because the body can react and then quickly return to normal once the situation is dealt with. However, the stress response has not evolved to deal with the long-term stressors of everyday modern life. We can now trigger the same physiological response that prepares us to run from a lion just by worrying about a stressful situation. In these mentally-induced cases of the stress response, the chemicals and energy reserves that are involved in the stress response are not used as efficiently as they would be if there were actually a lion to fight or run from. Thus, these chemicals and energy reserves have nowhere to go and end up accumulating in the body. Eventually, this buildup takes its toll on the body, which wears down and becomes more prone to a variety of diseases.

A Closer Look at the Stress Pathways^

The stress response begins in both the nervous system (which reacts almost immediately) and the endocrine system (which reacts more slowly). The two major stress response systems are the sympathetic-adrenal medullary (SAM) system (the nervous system’s response) and the hypothalamic-pituitary-adrenal (HPA) axis (the endocrine system’s response). These two systems function to create a precise homeostatic balance. The problem with chronic stress lies in the fact that the SAM system and HPA axis are not isolated systems and they impact numerous biological functions. Thus, they have the potential to protect or harm other parts of the body such as the immune system, the reproductive system, the digestive system (also known as the gastrointestinal (GI) tract), the heart, and even the brain.

The SAM System^

The SAM system is commonly referred to as the “fight or flight” response because it prepares the body to run away from a stressor or stay and fight it. When the SAM system is activated, the brain sends a message down the spinal cord to a part of the body called the adrenal medulla, signaling it to release a chemical messenger called epinephrine. Epinephrine circulates throughout the bloodstream and ensures that all the cells of the body are equally stimulated. This is why the stress response is non-specific. In addition, a chemical messenger called norepinephrine is released by nerve cells onto particular glands and muscles. In this way, the SAM system contributes to several changes in the body’s physiology. It quickens the heartbeat, raises the blood pressure, dilates the pupils, inhibits the GI tract, and increases metabolism. These changes allow energy to be used in the most immediately important way – more energy is taken up by muscles, which is what we need if we want to be able to run away from a ferocious lion.

The HPA Axis^

The HPA axis is mainly involved in the long-term stress response. The purpose of the HPA axis is to increase the amount of usable energy in the body and direct it to the places it is most needed. The HPA axis begins in the hypothalamus, which is located at the base of the brain and carries out its job throughout the body using a variety of hormones. The hypothalamus communicates with other parts of the brain and body, and produces hormones that either stimulate or inhibit the release of other hormones from another region of the brain called the anterior pituitary. When the brain detects a stressor, the hypothalamus releases adrenocorticotropin hormone (ACTH). ACTH goes on to stimulate a part of the body located just above the kidneys called the adrenal cortex to synthesize and release chemicals known as glucocorticoids. Glucocorticoids are a class of steroid hormones that includes cortisone, cortisol, and corticosterone. For more information on cortisol, click here.

Fig AN-1: Hypothalamic-Pituitary-Adrenal (HPA) Axis

Glucocorticoids regulate blood pressure and cardiovascular function, as well as the body’s use of proteins, carbohydrates, and fats. Glucocorticoid release increases in response to any type of stressor (physical or emotional) and causes the breakdown of stored nutrients into usable forms of energy. Fat, protein, and glycogen are broken down into different products so that they can be used by the body. Triglycerides (the main component of fat) are broken down in the fat cells, causing free fatty acids to pour into the bloodstream. Glycogen is degraded to its usable form, glucose, in cells throughout the body and eventually enters the bloodstream as well. Protein is converted back to its building blocks of individual amino acids. These amino acids are then used by the liver to make sugar (glucose) for energy. This raises the level of energy resources in the blood so they can be used to feed the brain and other essential organs. Glucocorticoids also inhibit non-essential functions such as growth, reproduction, and inflammation. (For more information on glucocorticoids and inflammation, click here.) Basically, the long-term stress response ensures that the brain and other organs essential to the stress response have adequate energy sources and that non-essential organs and processes don´t drain these energy sources.

Fig AN-2: The Provision Of Energy By Glucocorticoid Release

Harmful Effects of the Stress Response^

Stress can be summarized by the following paradox: It protects under critical conditions, but when activated chronically it can cause damage and accelerate disease. If we experience every day as an emergency, we will pay the price. If we constantly mobilize energy instead of storing it, we will never have any surplus energy and this will eventually lead to fatigue. If our blood pressure rises every time we think about paying the mortgage or meeting a deadline, then we greatly increase the risk of developing cardiovascular disease. This is especially important because heart disease is the leading cause of death for people with HD. If we constantly turn off long-term building projects, then nothing ends up getting repaired. If our immune system is suppressed, we are less likely to resist a variety of diseases. Let´s look into each of the negative effects of stress in more detail.

Stress and cardiovascular disease^

In stressful situations such as running away from a lion, we change cardiovascular function to divert more blood to our muscles. In this case, the blood that gets to the muscles carries enough energy resources to meet the muscles´ energy demand. However, when we are sitting in traffic worrying about being late we still divert more blood to the muscles because of the same stress response. This causes the blood vessels to work very hard. If we do this on a regular basis, the inner lining of the vessels begins to tear and pit. Once this layer is damaged, the fatty acids and glucose that are released into our blood by the stress response start to work their way beneath the inner lining and stick there. There is also evidence that during stress, red blood cells are more likely to clump together underneath the torn lining. Eventually, blood flow through the vessels decreases so much that it causes plaques to accumulate underneath the lining of blood vessels, a condition known as atherosclerosis. Another way that the stress response leads to heart disease is through the release of a protein called fibrinogen, which speeds up the clotting process. Clotting helps us in an emergency by keeping bleeding to a minimum if we are injured so that we can still escape. However, activating this response repeatedly can be very dangerous because a high level of fibrinogen is a risk factor for increased blood clotting and heart attack or stroke.

Stress and the immune system^

The stress response leads to a suppression of the immune system. The immune system is restrained because when we are running away from a lion, it doesn´t make sense to use energy to fight against diseases that will take a lot longer to kill us than the lion will. Our bodies are really smart; they focus on what is most important at the present moment. However, if we activate the stress response unnecessarily for prolonged periods of time, our health will eventually pay the price. With the immune system not running at full capacity, we are not being able to rally the necessary antibodies to fight off infections and diseases. The main way that the immune system is suppressed is through glucocorticoids. Glucocorticoids shrink the thymus gland, which is located in the chest under the breastbone and is critically important in the body´s response to disease invasion. In addition, glucocorticoids stop making and reduce the responsiveness of lymphocytes (also known as white blood cells). Lymphocytes are incredibly important specialized cells that fight infections. Amazingly, glucocorticoids can actually enter a lymphocyte and kill it by causing it to make a protein that destroys its own DNA.

Stress and the Brain^

The nerve cells that are affected by Huntington´s disease are distinct from the nerve cells that are affected by stress. HD causes degeneration of nerve cells in the basal ganglia and other areas of the brain, whereas stress mainly causes degeneration of nerve cells in the part of the brain called the hippocampus. Although not directly related to HD, stress is nevertheless related to the progression of the disease because it adds to the neurodegeneration that is already taking place.

Chronic stress can alter nerve cells, brain structure, and brain function. Normal nerve cells are like miniature trees with a lot of branches. These “branches” are called dendrites, and they are the structures that connect one nerve cell to many other nerve cells. Each of these connections is separated by a very short space called a synapse. One nerve cell communicates with another nerve cell by sending a chemical signal called a neurotransmitter across the synapse and onto the receiving nerve cell´s dendrites. (For more on nerve cell structure and function, click here.)

As we have already discussed, stress causes the release of glucocorticoids. Glucorticoids go on to cause the branches of the dendrites to become shorter and less widespread, which means that the affected nerve cell cannot connect to as many other nerve cells as it used to. With fewer connections, it does not receive as much information as it should. This “de-branching” occurs mainly in the hippocampus, which is very important for learning and memory. The hippocampus normally contains a lot of glucocorticoids. However, in the case of chronic stress, having too many glucocorticoids leads to the de-branching of nerve cell dendrites and interferes with nerve cell communication. (For more information on neuroplasticity and the significance of shortened branches, click here.)

Additionally, glucocorticoids make it difficult for nerve cells in the hippocampus to get enough glucose. Not having enough glucose makes these nerve cells more vulnerable to other insults, such as a lack of oxygen or loss of blood supply. As we have discussed above, excess glucocorticoids cause the nerve cells to lose their connections to other nerve cells. This phenomena, combined with their heightened vulnerability, causes nerve cells to eventually lose their function and die. This process occurs in people with Cushing´s syndrome. These patients produce massive amounts of glucocorticoids, which makes them a good example of how an overreactive stress response affects the brain. Studies have revealed that individuals with Cushing´s syndrome have a small hippocampus resulting in memory problems.

In addition to killing nerve cells, glucocorticoids can cause even more problems in the hippocampus because the hippocampus itself helps to run the glucocorticoid negative feedback cycle. In a negative feedback cycle, one chemical is released that stops the production of the main chemical when there is enough of it in the body. In the glucocorticoid negative feedback cycle, the hippocampus helps stop the release of glucocorticoids when there is enough of it in the body. When the hippocampus shrinks due to nerve cell death, it becomes less able to shut off the release of glucocorticoids. In this devastating cycle, called the glucocorticoid degenerative cascade, glucocorticoids damage the hippocampus and impair its ability to stop further production of glucocorticoids. This leads to the production of more glucocorticoids which, in addition to its other harmful effects, damages the hippocampus even further.

Why do we even have glucocorticoids?^

All of this information makes it sound like glucocorticoids are nothing but trouble. You might be thinking, “If they do so much damage, then why do we even have them in our bodies?” And why in the world would doctors prescribe them to certain patients? Glucocorticoids are actually essential to the body and we would not be able to survive the rigors of daily life without them. In studies of rats that are unable to secrete glucocorticoids, normal inflammatory responses (which are part of the immune system´s response to infection) spiral out of control. Thus, a certain amount of glucocorticoids is necessary for health, and certain amounts can be prescribed to patients to treat inflammation. (For more information on inflammation, click here.) Taken in low doses, glucocorticoids are fairly safe. However, if they are taken in large doses, or are constantly mobilized during chronic stress, they can begin many of the harmful processes that we just talked about.

Stress and HD^

It is now evident that stress is capable of causing a range of complications. While all of these complications are not necessarily directly related to the progression of HD, they nonetheless have an effect on the overall health of the individual. It is very likely that a person with HD is also affected by different kinds of daily stress. Based upon the findings in this section, one could predict that if there are two identical twins who both have HD, then the twin with lower stress will probably be in much better general health and live longer than the twin with higher stress, given that all other things are equal. It is important to keep stress to a minimum, regardless of whether or not one has HD.

Stress Management^

We are not able to ward off all of life´s stressors, nor can we simply flip a switch to bring our heart rate down when we want to stay calm. Given the severity of Huntington´s disease, it is quite likely that many people with HD or people at risk for inheriting HD suffer from chronic stress. With all the information about the effects of stress on heart disease, the immune system, and brain cell loss, this may seem a bit depressing. However, there is hope. Preserving our health in a crisis – even in an ongoing state of crisis – is well within our grasp. Despite the many ways that stress can wreak havoc on our bodies, we do not all collapse or fall victim to stress-related diseases. Given the same stressors, we vary considerably in how our bodies and minds cope. The power of the physiological stress response often depends on how the individual perceives the stressor. In one study, two rats received an identical series of shocks at the same intensity. One, however, had a bar of wood in its cage to gnaw on after the shock. Given this outlet, the rat with the wood had far less of a physiological response despite experiencing the same physical stressor. Other studies on rats show the protective effects of a warning light that precedes the stressor, a lever to press that gives the rat an illusion of control, and the presence of another rat for comfort. Critical factors that intensify psychological stress include loss of control, lack of predictability, lack of outlets for frustration, and a perception of things worsening. While these studies were done on rats, the findings do translate somewhat to humans. Below are some of the steps that people can take to help counteract the effects of stressors:


Exercise strengthens nearly every aspect of the body. Numerous studies have shown that simple walking can prevent heart disease. In a study of 2,500 elderly men, heart disease risk went down depending on the distance that they walked. This is because walking reduces stress and when the stress response is lowered, smaller amounts of fatty acids, glucose and stress response chemicals like glucocorticoids are released into the bloodstream. With fewer stress response chemicals in the blood stream the blood vessels don´t get clogged as easily. Exercise can also improve depression and anxiety. Many studies have shown a relationship between exercise and mood. Exercise promotes wakefulness and relaxation, and improves quality of sleep. Being well rested helps the body recover from the stress response.


Relaxation through meditation, yoga, visualization, and a variety of other activities can help reduce the stress response. Participating in relaxing activities promotes lower blood pressure, slower breathing, reduced metabolism and decreased muscle tension. All of these changes in the body counteract the negative effects of stress.

Social support^

Social contacts, friends, and family relationships can also help people live less stressful lives. One study showed that people who are forced to give a public speech have a less dramatic cardiovascular response (it was easier to breathe and their hearts didn´t beat as fast) when they have a supportive friend in the audience. Another study found that male baboons with more playmates and grooming buddies have lower glucocorticoid levels than males with fewer attachments. Social support is incredibly helpful when coping with disease. In a study of men who were infected with HIV but did not have the advanced symptoms of AIDS, the infection progressed more quickly in those men who reported less satisfaction with social support. In the famous Alameda county study, the findings showed that people who lacked social and community ties were more likely to die in the follow-up period than people with extensive contacts. This implies that people with HD can benefit greatly from the love and support of family and friends.

Maintain a Healthy Lifestyle^

Poor lifestyle choices can affect the HPA axis and increase levels of glucocorticoids, even if we aren´t actually stressing about something. Therefore, it is important that we do not worsen the stress response by drinking or smoking excessively or by eating unhealthy foods. A study found that stressed individuals eat more sweet, fatty foods than non-stressed individuals, although it is difficult to determine which came first, the lifestyle or stress. This is important because fatty foods can accelerate the development of heart disease, which is one of the leading causes of death among people with HD. Maintaining a healthy diet is one way that we can keep the stress response from spiraling out of control. Stress weakens the immune system, making it harder to fight off infection. Smoking is incredibly hazardous to the lungs, making it more likely that someone under added stress (such as a person with HD) would get a respiratory disease. Furthermore, smoking may cause respiratory complications to appear earlier in the disease process. Since respiratory diseases are one of the leading causes of death among people with HD, it is especially unwise for people with HD to smoke.

Gain Control^

Stress is often related to the anxiety caused by a feeling of being out of control. Sometimes, the processes in our bodies that result in disease are inevitable (as is the case with HD) and it is important not to feel guilty or discouraged by this. It is also important for people with HD to understand as much as they can about their health and health problems – stress-related and otherwise – and take measures to bolster their well-being, while working with doctors and following approved treatment plans.

For further reading^

  1. A.A. Hakiim et al. “Effects of walking on coronary heart disease in elderly men: The Honolulu Heart Program.” Circulation 100 (1999): 9-13.
    This is a fairly easy to read study that showed the beneficial effects of walking.
  2. Berkman, L.F. “Social networks, host resistance and mortality: a nine-year follow-up study of Alameda county residents.” American Journal of Epidemiology 109 (1979): 186-204.
    This article goes into depth about the methodology and results of the Alameda study.
  3. Esch T, Stefano GB, Fricchione GL, Benson H. “The role of stress in neurodegenerative diseases and mental disorders.” Neuroendocrinology Letters 23 (2002): 199-208. Online.
    This is a paper that explains how stress affects various neurodegenerative diseases. It does not address Huntington´s disease specifically and is of medium difficulty.
  4. Gerin, W. et al. “Social support in social interaction: A moderator of cardiovascular activity.” Psychosomatic Medicine 54 (1992): 324.
    This is a very interesting study that showed that people become less stressed when giving a public speech if they have a friend or loved one in the audience. It is fairly easy to read.
  5. Leserman, J. et al. “Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS.” American Journal of Psychiatry. 157 (2000): 1221-1228.
    This is a study that examined whether or not social support influenced the onset of AIDS. It is of medium difficulty.
  6. Oliver, G. et al. “Stress and food choice: A laboratory study,” Psychosomatic Medicine. 62 (2000): 853-865.
    This is a laboratory study that investigated whether acute stress influenced food choice during a meal. It is of medium-difficulty.
  7. Sapolsky, Robert. Stress, the Aging Brain, and the Mechanisms of Neuron Death. Cambridge: A Bradford Book, 1992.
    This is a highly informative book that details exactly what stress does to nerve cells in the brain. It is fairly difficult reading.
  8. Sapolsky, Robert. Why Zebras Don´t Get Ulcers. New York: WH Freeman and Company, 1994.
    This is very enjoyable book that can help the layperson understand the mechanisms behind the stress response.

-D. McGee, 04/18/05; recorded by B. Tatum 8/21/12


Driving and Huntington's Disease


Once a person is diagnosed with HD or tests positive for the HD allele, many adjustments will have to be made in due course in his or her life. For example, some people will change their diet, others will increase their amount of daily exercise, and some will do both. In addition to such lifestyle changes, some who are symptomatic may choose to limit or even stop former daily activities, such as driving automobiles. Whether it is always necessary to cease driving still remains to be seen, yet studies show that the vast majority of HD patients end up turning in their keys.

The liberty to drive is often taken for granted by the population at large. However, for people suffering from neurodegenerative diseases like HD, a loss in the ability to drive may stimulate feelings of helplessness and depression due to a loss of independence. HD patients often become dependent on family members and friends to take them out and drive them from place to place, especially in areas where public transportation is inadequate. This dependence can be taxing for both parties involved, and it is sometimes viewed as an added burden.

The ability to drive can be significantly impaired by HD, and this is an issue which should not be ignored when making lifestyle adjustments. However, an HD diagnosis does not automatically mean that a person should cease driving. Since different people are in different stages of the disease, to continue or stop driving altogether is a personal decision that should be made with input from family, friends and physicians.

Why do people with HD give up driving?^

In many cases, people with the symptoms of HD will give up driving because they think the disease has compromised their ability to be a safe driver. If in doubt, an independent evaluation of driving safety can be obtained from a local driving school or “driver’s ed” instructor. In these instances, people will stop driving in order to prevent accidents, bodily harm and even death. Automobile collisions and mishaps can also lead to increased financial burdens on the family, such as property loss, medical bills and insurance claims.

Specifically, a main reason why many HD patients give up driving is the way the disease affects their mental capacity. Many individuals with HD have problems with divided attention, that is, the ability to split one’s attention between two or more tasks simultaneously. Often, people with HD will not be able to concentrate on two activities at the same time when driving, resulting in a failure to stop appropriately at red lights and stop signs, in a failure to stay in one driving lane at a time, or in other accident-causing actions. These actions can result from being distracted in the car by having conversations with passengers, listening to the radio or CD player, or concentrating on matters other than driving.

Another issue that impairs one’s ability to drive is implicit memory. Those with HD usually have problems with this type of procedural, “unconscious” memory. Since driving involves motor function, it falls under the category of implicit memory, and drivers might find themselves getting lost easily and unable to follow directions. Thus, a greater amount of “conscious” memory and concentration is needed by individuals with HD in order to drive a car without any problems. (For more information on the cognitive symptoms of HD, click here).

Finally, physical impairments, such as involuntary movements of the body, hands and feet – all signs of chorea, also undermine driving ability. Any uncoordinated movements of the driver in the car can lead to problems with speeding, stopping, turning or simply driving in a straight line, to name a few.

Currently, there is very little research conducted on driving and HD patients, although several research centers are looking to explore the topic in more in-depth ways. In one previous study, a group of 73 HD patients were given clinical and cognitive examinations as well as a questionnaire in order to determine their driving history and competency. The study found that people with HD are at a greater risk for having automobile accidents. They also performed worse on driving-related tasks and were more likely to have been in an auto collision in the past two years than the control population.

These findings do not mean, however, that everyone diagnosed with HD should immediately stop driving. Rather, these findings reveal that a car can be a very distracting place regardless of one’s condition, and that people with HD must be extra careful if they choose to drive.

What does the law have to say about HD and driving?^

To date, there is no uniform, national law concerning driving with HD or other neurodegenerative disease. Various states have different laws and practices addressing the issue. Across the nation though, studies have shown that the majority of patients stop driving voluntarily, rather than because of observance with the law.

Currently, nine states (California, Delaware, Georgia, Nevada, New Jersey, Oregon, Pennsylvania, Utah, and West Virginia) have laws requiring that doctors identify to a local health office their patients at least 14 years of age or older with “high risk” diseases that could compromise their driving ability. HD, Alzheimer’s disease, Parkinson’s disease, epilepsy, dementia, seizure disorders, narcolepsy and other similar conditions are all candidates for reporting. Since they are required by law, physicians are exempt from criminal and civil liability for reporting on patients but in fact, actual reports are rare.

If a patient is reported as having a compromising condition, then he or she must fill out a medical evaluation form in addition to being tested by the DMV. Based on the results, the DMV will then take no action if no problem has been found, or they may decide to issue a restricted/limited license or suspend/revoke the license if the driver is found to be unsafe. If a license is revoked, then only after a set period of time could a person come back, re-test and re-apply for a new driver’s license. If action is taken against a patient’s driver’s license, then he or she has 10 days in which to request a hearing after being contacted by the DMV in order to appeal the decision. Otherwise, the right to a hearing is forfeited.

To find out information for your particular state and its policy on driving with a medical condition, call or visit the web site of your local Department of Motor Vehicles.

How can individuals with HD drive safely?^

Driving is not an impossible task for those with HD. It takes an extra amount of effort and may be exhausting, since increased concentration is required by individuals in order to drive safely. A person with HD should be monitored for a period of time before any decisions are made to continue or discontinue driving. Independent testing and/or driver’s training should be considered as can be arranged with a local driving school.

Certain steps can be taken by those with HD and their friends and family to ensure that the driver remains safe. Limiting passenger conversations, avoiding cell phone calls, turning off the radio/stereo when traveling, and trying to maintain full concentration on the road are all good ideas when it comes to driving.

Individuals with HD should also try to avoid driving at high speeds and traveling in areas where there is a lot of traffic. Drivers should also be mindful of certain times of the day such as rush hour and when there is bad weather. If a person with HD needs to travel at these times, then it would probably be best either to use public transportation or to find a ride from a friend or family member.

Additionally, planning plays an important role when it comes to driving. Individuals with HD should consider combining multiple driving trips into one, finding and then sticking to low-traffic and low-speed routes, and always informing friends and family about where, when and how long he or she intends to travel. It is always advisable for persons with HD to plan a trip and think over options before hitting the road.

For further reading^

  • Rebok GW, Bylsma FW, Keyl PM, Brandt J, Folstein SE. 1995. Automobile driving in Huntington’s disease. Movement Disorders. Nov;10(6):778-87.
  • Hawley, CA. 2001. Return to driving after head injury. Journal of Neurology, Neurosurgery and Psychiatry with Practical Neurology. 70:761-766
  • Lowit A, van Teijlingen ER. 2005. Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington’s disease patients. BMC Family Practice. Sep 14;6:38.

-A. Haque, 11/12/06

Complementary and Alternative Medicine


This section contains information about a variety of practices and dietary supplements that are thought by some to alleviate HD symptoms in some patients. The information presented here is intended for informational purposes only. HOPES researchers are not medical professionals, and we do not recommend any particular treatments. It is imperative that all patients speak to their physicians before beginning any course of treatment, regardless of whether the treatment is available without a prescription.

What is Complementary and Alternative Medicine (CAM)?^

According to the National Center for Complementary and Alternative Medicine (NCCAM), complementary and alternative medicine (CAM) “is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.” Complementary medicine is used together with conventional medicine. For example, a patient suffering from a cold might take both vitamin C and an over-the-counter decongestant, or a patient who has just had surgery and has limited motility might add massage to his recovery regiment, in addition to conventional physical therapy. Alternative medicine, on the other hand, is used instead of conventional practices, such as when a person with cancer refuses chemotherapy or surgery and instead chooses to take injections of shark cartilage.

Many people pick and choose from a variety of conventional and CAM therapies, seeking the opinions of medical doctors (MDs) or CAM practitioners, depending on their needs. Some patients turn to CAM because they believe these treatments are safer or more effective than conventional treatments. Others choose CAM by default because there are no conventional treatments for their illnesses.

For further reading:^

  • National Center for Complementary and Alternative Medicine. Online.
    This page contains a lot of information about alternative medicine, including a description of different CAM treatments, CAM-related press releases, and a list of CAM clinical trials.

What Types of CAM Therapies are Available?^

Several different CAM therapies are currently available in the United States, although most of these treatments are not covered by insurance and many do not have scientific verification. Each alternative medicine system has a different theory about how the human body functions in health and illness. As a result, each system promotes its own array of remedies and preventative measures.

One alternative medical system is homeopathy. The central belief of homeopathy is that “like cures like.” In this system, extremely dilute amounts of substances that can cause a patient’s symptoms (when given in much higher doses) are given to the patient to treat his or her symptoms. As the National Center for Homeopathy explains, “Instead of looking upon the symptoms as something wrong which must be set right, we see them as signs of the way the body is attempting to help itself. Instead of trying to stop the cough with suppressants, as conventional medicine does, a homeopath will give a remedy that will cause a cough in a healthy person, and thus stimulate the ill body to restore itself.” However, a recent study found little evidence for the effectiveness of homeopathic remedies and urged patients not to substitute homeopathy for proven conventional treatments. Thus, while the issue is still up for debate, patients interested in pursuing homeopathic remedies should tread with caution and consult their physicians for advice.

Ayurveda and traditional Chinese medicine (TCM) are two alternative medical systems that were developed in Asia and have gained greater recognition in the US over the last several years. Ayurveda, a system that relies on herbal and dietary remedies and focuses on the use of mind, body, and spirit in disease prevention and treatment, has been practiced in India for thousands of years. According to Ayurveda, each human being is made up of a unique combination of the five elements: fire, water, earth, air, and ether. These elements combine to determine the balance of doshas, energetic and physiological qualities that are similar to the humoral system of the Ancient Greeks. Practitioners of Ayurveda believe that illness occurs when the body’s physical state is unbalanced. Although some current research on Ayurvedic techniques appears promising, the English-language literature has virtually no large-scale, controlled clinical studies evaluating the effectiveness of this system.

The theory behind traditional Chinese medicine is that the human body “is subject to constant battling between opposing forces such as heat and cold, male and female, [and] joy and sadness, which manifest themselves … as too much or too little activity in particular organs. An imbalance between any of these forces can cause a blockage in the flow of qi [pronounce “chee”], or vital energy, traveling through the body along invisible pathways known as meridians.” Practitioners have many techniques to unblock the flow of qi, including medication, herbs, acupuncture, massage, and exercises. Certain TCM treatments have been proven effective in treating a variety of medical conditions, while other treatments appear to be ineffective or even toxic.

For further reading:^

  • National Center for Homeopathy. Online.
    This page describes the difference between homeopathy and conventional medicine, gives an overview of homeopathic drug products and prescription practices, and explains the history of homeopathy.
  • Jonas WB, Kaptchuk TJ, Linde K. A critical overview of homeopathy. Annals of Internal Medicine 2003; 138(5): 393-399.
    A fairly easy to read paper that describes homeopathy and discusses some placebo-controlled studies of the system.
  • A Healthy Me – Traditional Chinese Medicine.Online.
    This page describes the theory behind TCM treatments and provides information on how to find a practitioner.

Are CAM Treatments Safe and Effective?^

As explained in the previous section, a number of different CAM treatments are available in the US, but most of them have never undergone clinical trials (i.e., been tested on humans in a controlled, systematic way). Of the treatments that have been tested, some have been shown to be effective, while others have been shown to be useless or even dangerous. However, virtually all CAM treatments, even those that have been found to be completely ineffective, have some enthusiastic supporters. How can people claim that a treatment works when clinical studies have clearly shown that it does not? In these cases, it is likely that patients who say that the treatment was successful have actually experienced the placebo effect, which is when an inert substance (i.e., a substance that does not affect the body) leads to improvement in a person’s medical condition. Psychologists have proposed that this phenomenon is a result of the patient’s belief that the treatment will succeed. In other words, some patients get better simply because they believe that whatever they are doing will help them get better, not because they are using treatments with actual physiological effects. In most clinical studies, a group of patients that receives a treatment is compared to a group of patients that receives a placebo, and neither group knows which treatment they are receiving. This study design allows researchers to determine whether the treatment in question is more effective than the placebo.

Since some CAM treatments can be harmful, and many of them can be expensive, it is important for patients to make thoughtful and informed decisions about which ones, if any, to include in their treatment regimens. The growing body of research on CAM treatments can help patients decide which ones are best for them.

For further reading:^

  • Beecher H.K. The powerful placebo. JAMA 1955; 159(17): 1602-1606.
    An easy-to-read paper that describes the effects of placebos and explains the reasons for their use.

Potential CAM Treatments for Huntington’s Disease^

Currently, there is no cure for Huntington’s disease. However, just as some medications can alleviate symptoms, some complementary and alternative medicine (abbreviated “CAM”) treatments can help patients function better and even slow the course of the disease. HOPES offers this information only for educational purposes. We are not medical professionals, and we do not recommend any particular treatments. We advise readers to consult their physicians about all CAM techniques.

While some CAM techniques can be very bizarre, others are simply everyday practices of good physical and mental health, such as exercise and environmental stimulation.

A very common CAM practice is taking dietary supplements, a topic that is further discussed below.

What Are Dietary Supplements?^

The Office of Dietary Supplements at the National Institutes of Health in the U.S. defines a dietary supplement as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.”

Consumers can purchase dietary supplements at many supermarkets, health food stores, and online retailers. Due to licensing requirements, many CAM treatments are sold as dietary supplements. Some research suggests that certain dietary supplements may help alleviate the symptoms of HD. A few dietary supplements that may actually help with HD are: creatine, fatty acids, and vitamin C.

How Are Dietary Supplements Different from Medications?^

One of the most important differences between dietary supplements and over-the-counter medications is the way in which the US government regulates them. In order for a medication to be approved, it must pass through several clinical trials (i.e., the medication must be pre-tested on humans). Afterward, the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research examines the data from the clinical trials and evaluates the risks and benefits of the drug. In contrast, the FDA regulates dietary supplements as foods, not as drugs, which means that dietary supplements can be sold in the US without FDA approval. Manufacturers do not have to test the supplements’ safety or effectiveness. Additionally, the FDA does not regulate the content of supplements. In other words, a supplement might contain higher or lower amounts of the active ingredient than it lists the label, it might be contaminated, or it might not even contain the active ingredient at all.

For further reading:^

  1. Office of Dietary Supplements. Online.
    This is a very informative page that provides fact sheets on dietary supplements and lots of related research articles and news bulletins.
  2. The CDER Handbook. Online.
    This page provides information about drug development, review, and approval.
  3. What’s in a Bottle? Introduction to Dietary Supplements. Online.
    This easy-to-read page provides a good overview of dietary supplements.

-M. Schapiro, 5-20-04, -K. Taub, Updated 8-11-05; recorded by B. Tatum, 8/21/12


Fatty Acids




Today in the U.S., we are commonly instructed to lower our fat intake because word is out that fats are bad. Low-fat, non-fat, and even “fake fat” food products dominate supermarket shelves. Consumers typically fear fat in any form. However, not all fats are bad. In fact, some types of fats are actually necessary for life and health and should not be eliminated from the diet. This chapter examines the different types of fats, as well as the effect that these fats can have on the brain. In addition, this chapter reveals how optimizing the amount and type of fat in the diet may help combat Huntington´s disease (HD).

Saturated vs. Unsaturated Fat^

The whole of issue of fat in the diet has become very confusing, mainly because there are so many different types of fat. Essentially, there are two broad categories of fat: saturated fat and unsaturated fat. These two types of fat differ in their chemical structure. Saturated fatty acids (the building blocks of saturated fat) have no double bonds (a particular kind of chemical link between adjoining molecules) and this lack of double bonds means that there are no gaps in the fatty acid chain: it is packed with CH2 molecules. Unsaturated fatty acids (the building blocks of unsaturated fat), on the other hand, have double bonds and these double bonds break up the string of CH2´s and create gaps within the fatty acid chain. See figure 1 for a depiction of the difference between saturated and unsaturated fatty acids. We will explore how this difference in chemical structure affects how different types of fat interact with the body below.

Saturated fats (meats, butter, dairy products) are solid at room temperature, whereas unsaturated fats (vegetable oils) are liquid at room temperature. Due to their difference in chemical structure, saturated fats and unsaturated fats exert different effects within the body. Because saturated fatty acid chains have no gaps, they are able to pack together very tightly. When these tightly packed saturated fatty acids enter the bloodstream, they increase levels of “bad” cholesterol known as low-density lipoprotein (LDL) cholesterol and clog arteries. In comparison, unsaturated fats do not increase “bad” cholesterol and, in fact, are able to increase levels of “good” cholesterol known as high-density lipoprotein (HDL) cholesterol. HDL is able to grab LDL and escort it to the liver where it is broken down and eventually removed from the body. Thus, by increasing levels of HDL, unsaturated fats are able to protect against the damage done by saturated fats. Since heart disease is a leading cause of death for people with HD, it is especially important to keep the heart healthy and limit intake of saturated fat. (For more information on the many complications of HD, including heart disease, click here.) And as we will see below, there are even more reasons than heart disease for people with HD to be conscientious about the types of fat that they consume.

Trans fat^

Because saturated fats were shown to be so unhealthy, food manufacturers decided to start using more unsaturated fats. The problem is that unsaturated fats spoil quickly. Food manufacturers solved this problem by putting unsaturated fats through the process of hydrogenation, which essentially alters the chemical structure of unsaturated fats and makes them more solid and long-lasting. However, when unsaturated fat is hydrogenated, a new fat called trans fat is produced. Fried foods, doughnuts, cookies, and crackers all contain high levels of trans fat. Trans fat rarely exists in nature and has been shown to be toxic to the body. Not only does it increase levels of “bad” cholesterol, it also decreases levels of “good” cholesterol. Thus, it has no redeeming qualities within the body and, as will be discussed later, it can worsen HD symptoms.

The relation between fat and nerve cells^

Nutrition is an integral component of our daily life routine and it has the potential to modulate brain health and function. Although it may at first seem strange, fat is essential for brain development and maintenance. In fact, about two-thirds of the brain is composed of fat, which may come as a surprising statistic. Where is all that fat? It is found in two places associated with nerve cells themselves. First, the protective covering of nerve cells called myelin is 70% fat. More importantly, the membranes of nerve cells are made of a thin double-layer of fatty acid molecules. After the body breaks down fat from the diet into fatty acids, the brain then uses these fatty acids by incorporating them into its cell membranes. Nerve cell membranes are extremely important because their composition determines what is able to pass into and out of the cell. Oxygen, glucose, and the nutrients that the cell needs to survive all must pass through the membrane and into the cell´s interior. When saturated fatty acids are incorporated into normally very fluid cell membranes, they pack very tightly because saturated fatty acid chains have no gaps. Thus, essential nutrients are unable to get into the cell, making the cell less healthy and more prone to injury. In contrast, unsaturated fats can be beneficial to nerve cells because they prevent the tight packing of fatty acids in the membrane. Unsaturated fatty acids have gaps in their chains and these gaps allow for a certain amount of “fluidity.”

Membrane fluidity is absolutely essential for the optimal function of most cells in the body, but it is especially important for nerve cells. In addition to letting in essential nutrients and keeping out harmful substances, nerve cell membranes also contain proteins that act as receptors for some neurotransmitters. Neurotransmitters are the chemical messengers that nerve cells use to communicate with each other. (For more information on neurotransmitters and their role in HD, click here). In order for the receptors to be able to recognize neurotransmitters and send along the messages that they contain, the nerve cell membrane must be fluid. If the nerve cell membrane is too rigid, the receptors on the membrane become less capable of recognizing neurotransmitters and passing along messages to the nerve cell. Often, the messages contained in neurotransmitters are critical to the survival of the nerve cell. Thus, membrane composition is extremely important because it influences nerve cells´ ability to communicate with each other and, ultimately, survive.

Studies reveal that optimal membrane composition is obtained when one consumes equal amounts of saturated and unsaturated fat. However, nutritional studies show that the average North American eats three times as much saturated fat as unsaturated fat! The addition of trans fat to the diet has made the situation even worse. Let us consider each fat in the context of our cells. Although too much saturated fat is bad, a certain amount is necessary for the optimal functioning of the membrane. On the other hand, the cell membrane has absolutely no use for trans fat. When trans fat gets incorporated into nerve cell membranes, the membranes become less capable of performing many essential functions, making the nerve cells more prone to a variety of insults.

How fat affects people with HD^

Nerve cell Communication^

Excessive consumption of saturated fat and trans fat can be particularly hazardous for people with HD. Even without any dietary influences, the HD disease process causes some nerve cells in the brain to become less able to communicate with each other, which contributes to these nerve cells losing function and eventually dying. Consuming excessive amounts of saturated fat can worsen this situation by making it even harder for nerve cells to communicate with each other via neurotransmitters. If the nerve cell membrane consists of too much saturated fat or trans fat, the nerve cell may be unable to receive messages from neurotransmitters. Often, these messages are essential for the survival of the cell. (For more information on the neurobiology of HD, click here.) Thus, it is clear that the amount and type of fat in the diet may influence the ability of nerve cells to survive. Replacing saturated fat and trans fat with unsaturated fat in the diet can enhance the ability of the nerve cell membrane to pass along necessary messages. It can also increase the fluidity of the nerve cell membrane, which makes it easier for the nerve cell to receive an adequate supply of oxygen and other essential nutrients. With the nerve cell membrane functioning as efficiently as possible, the nerve cell may be better able to deal with the harmful effects of HD. Thus, it may be possible for a person with HD to delay the onset and progression of HD symptoms simply by altering his or her fat consumption.

Oxidative stress^

In addition to negatively affecting membrane function, a diet high in saturated fat may also induce oxidative stress and decrease levels of a protein known to assist in nerve cell survival called brain-derived neurotrophic factor (BDNF). Increased oxidative stress and decreased BDNF would be highly damaging to a person with HD. When trying to combat a neurodegenerative disease such as HD, maximizing levels of BDNF is ideal because it may help combat the damage done by the disease. Thus, in the interest of maintaining levels of BDNF, one might consider limiting one´s consumption of saturated fat. In addition, keeping oxidative stress to a minimum is important for people with HD. Oxidative stress, a harmful process that injures cells and eventually causes them to die as a result of free radical damage, is thought to contribute significantly to the disease process of HD. (For more information about free radicals and HD, click here.) Although a certain amount of oxidative stress will inevitably occur due to aging, it is important for people with HD to be conscientious about not worsening oxidative stress from the food they eat. Since diet is a very controllable aspect of one´s lifestyle, limiting consumption of saturated fats is a great way for people with HD to ensure that they do not aggravate the damaging processes in their nerve cells any further. Although much more research needs to be done in this area, it seems likely that adjusting for less saturated fat in one´s diet could significantly slow down the progression of HD.

Getting the right type of unsaturated fat – essential fatty acids.^

In general, it is true that any type of unsaturated fat is better for the brain and body than either saturated fat or trans fat. However, there are many different types of unsaturated fat and some types of unsaturated fat are better for you than others. Monounsaturated fatty acids have only one double bound and thus only one gap in the fatty acid chain. Polyunsaturated fatty acids have many double bonds and many gaps within the fatty acid chain. All saturated and monounsaturated fats can be made within the body and, therefore, they do not need to be supplied through the diet. However, the body is unable to make two types of polyunsaturated fat and these must be obtained through the diet. The first type of polyunsaturated fat is alpha-linolenic acid (ALA), which belongs to the omega-3 family of fatty acids. ALA is found abundantly in flax seed (a fiber derived from plants) and flax oil, and is found in small quantities in canola oil, wheat germ, and dark green leafy vegetables such as spinach and broccoli. The second type of polyunsaturated fat that the body cannot make is linoleic acid (LA) and it belongs to the omega-6 family of fatty acids. LA is found in soy oil, sesame seeds, corn oil, and in most nuts. Because the body is unable to make these two fatty acids, they are an essential part of the diet. Hence, they are called essential fatty acids (EFA´s).


Once the body is supplied with the essential fatty acid ALA, it can convert it into DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid). Both DHA and EPA are great at lowering one´s risk for heart disease. In addition, DHA is essential for nervous system maintenance and development. Infants who have low amounts of DHA in their diet have reduced brain development. Accordingly, human milk is extremely rich in DHA. DHA is the most abundant fatty acid in nerve cell membranes and is thought to contribute significantly to the fluidity of the cell membrane. DHA is also found in the synapses between nerve cells and is thought to greatly aid the nerve cells in sending signals to each other. The problem is that DHA levels naturally decline as one gets older. If DHA is not supplied through the diet (from consuming ALA), then the nerve cell membranes begin to function sub-optimally. Perhaps this may explain why societies whose diets are high in DHA (such as the Inuit of the arctic who eat a lot of fish, a great source of DHA) have a lower incidence of neurodegenerative disorders.


The other essential fatty acid, LA, is converted to GLA (gamma linoleic acid) within the body. GLA eventually leads to the production of prostaglandins, which are molecules that help regulate inflammation and blood pressure. (For more information on essential fatty acids and inflammation, click here.) While LA is termed “essential,” it is not entirely good for the body. In fact, Americans tend to consume way too much of it. This overconsumption is a problem because it turns out that both ALA and LA compete for the same enzymes to produce their final product. In other words, if there is too much LA, then the enzymes will be busy converting LA into GLA and there will be no enzymes left to convert ALA into DHA. (For more information on how ALA and LA compete for enzymes, click here.)Thus, a balance of ALA and LA is essential for proper health. Studies show that the optimal ratio of LA to ALA is somewhere between 2:1 and 1:1. It is estimated that the ratio of LA to ALA for most Americans is around 20:1. This imbalance makes sense because typical foods such as cereal, eggs, poultry, bread, and baked goods are made from oils rich in LA. Foods rich in ALA are much harder to find. Often, dietary supplementation may be needed in order to get enough ALA.

In addition to consuming enough ALA, humans must be able to absorb it. Findings suggest that an inadequate intake of vitamin E results in decreased absorption of ALA. Thus, some experts suggest that vitamin E supplementation may be useful in conjunction with ALA supplementation.

As mentioned earlier, nerve cell membranes are critical in terms of maintaining the safety of the nerve cell. Not only are they responsible for letting in essential nutrients and expelling harmful substances, but they also help nerve cells communicate with each other. Thus, in a person with HD, it is especially important for the nerve cell membranes to be operating optimally because it can greatly aid in the survival of the nerve cells. DHA, a product of ALA, has been shown to keep nerve cell membranes operating at an optimal level. It stands to reason that if a person with HD obtains adequate amounts of ALA and fixes the skewed imbalance of LA to ALA, he or she may be able to prolong the life of his or her nerve cells, and this too would likely delay the progression of the disease.

A wrap-up on fatty acids and HD^

Fats play a significant role in the brain. Specifically, the amount and type of fat one consumes directly affects the composition of nerve cell membranes. The composition of nerve cell membranes is especially important for people with HD because it has the potential to protect the nerve cell from damage. Too much saturated fat or trans fat in the diet leads to stiff, rigid membranes and a loss of membrane fluidity. In addition, too much saturated fat and trans fat alters the shape and size of the nerve cell membrane, which ultimately makes it so that the nerve cells are less able to communicate with each other. By replacing saturated fat with unsaturated fat in the diet, a person with HD can help his or her nerve cell membranes to function as efficiently as possible. Furthermore, certain types of unsaturated fat are more beneficial than others. In particular, the essential fatty acid (EFA) called ALA, which leads to DHA as described above, is the most abundant and perhaps most important in the brain. Because ALA competes with LA, one must limit one´s consumption of LA in order to ensure adequate amounts of ALA.

In short, the research reviewed in this chapter indicates that a person with HD should strive to reduce the amount of saturated fat and trans fat in his or her diet and to increase the ratio of ALA to LA in his or her diet in order to ensure the optimal functioning of the nerve cell membranes. Better functioning membranes means healthier nerve cells and having healthier nerve cells may well postpone the onset of HD symptoms.

Research on essential fatty acids:^

Vaddadi, et al. (1999) examined the effect that essential fatty acid (EFA) supplementation can have on the symptoms in people with HD. In the study, there were 17 HD patients who all showed clinical signs of HD, such as chorea. Genetic testing confirmed that these 17 patients did indeed have HD. During the study, the patients were told to stick to the same routine and continue taking the same amounts and types of medication. Randomly, nine of the subjects were assigned to the treatment group and they were given capsules that contained essential fatty acids. The other eight subjects were assigned to the control group and they received placebo capsules that did not contain essential fatty acids (this group was used to compare to the group receiving treatment). The study was designed to last two years and the patients´ symptoms were assessed at the beginning of the study and at six-month intervals. Their symptoms were assessed using two Huntington´s disease rating scales.

After twenty months, the study had to be stopped on ethical grounds because it was clear that the treatment group was receiving a significant benefit from the essential fatty acid capsules. The subjects in the treatment group improved in motor skills and functional performance while the subjects in the control group deteriorated. The results indicated an actual improvement over the starting measurements for the treatment group and not merely a slowing of deterioration. Of the nine subjects in the treatment group, only one subject did not improve over baseline. Much of the separation in results between the two groups occurred during the first six months of the study, indicating that it does not take long for the effects of essential fatty acid supplementation to be seen. However, the study did have a few shortcomings. The sample size was small and the effect of any earlier treatments that the subjects may have tried is unknown. Also, the study was terminated early so the long-term benefits of essential fatty supplementation are unclear. The study also does not indicate how high a dose is required to produce an effect. Clearly, much more research needs to be done in this area.

Clifford, et al. (2002) looked at how essential fatty acid (EFA) supplementation affected a mouse model of HD. These specific mice have an HD-like allele and they develop late-onset nervous system deficits in a manner similar to the motor abnormalities of HD. The mice were randomly divided into two groups: a treatment group receiving a mixture of fatty acids and a control group receiving a placebo. Through mid-adulthood, mice in the control group experienced progressive shortening of stride length and complications in movement ability. These deficits were either not evident in the mice in the treatment group or were significantly decreased. The findings of the study indicate that early and sustained treatment with essential fatty acids may be able to protect against motor deficits in mice that have an HD-like allele, and thus may also be able to protect against motor deficits in people with HD.

For further reading^

  1. Aiguo, W. et al. “The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition.” European Journal of Neuroscience. 2004; 19(7): 1699-707.
    This is a technical scientific article that explains how a diet high in saturated fat can lead to oxidative stress and decreased levels of BDNF.
  2. Clifford, J.J. et al. “Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington´s disease.” Neuroscience. 2002; 109(1): 81-8.
    This article is fairly easy to read and it describes the study in which a mouse model of HD that received essential fatty acids showed improvements in motor abilities.
  3. Vaddadi, K.S. et al. A randomised, placebo-controlled, double blind study of treatment of Huntington´s disease with unsaturated fatty acids.” Neuroreport. 2002; 13: 29-33.
    This article is of medium difficulty. It describes the study in which essential fatty acid supplementation was examined among HD patients.

-D. McGee, 04/27/05


Curcumin, the Curry Spice

For many years, people around the world have been preparing their meals with an Indian spice called curry. Although most people who eat curry probably do so simply because of its pleasant taste, some current research suggests that the spice may actually have another important characteristic: it may be helpful in combating the effects of some neurodegenerative diseases. According to research on Alzheimer’s disease (AD), the disease-fighting effects of curry come from a compound called curcumin, which is a component of turmeric, the yellow spice that is used in most traditional curries. This chapter gives an overview of curcumin’s beneficial effects on AD and suggests possibilities for how curcumin may affect Huntington’s disease.

How Curry Relates to the Epidemiology of Alzheimer’s in Humans^

Scientists first became interested in studying curcumin when they looked into some statistics about the prevalence of AD in India, where curry is eaten in large quantities. In India, a relatively small proportion (1%) of people age 65 and older have AD. Additionally, in comparison to their American counterparts (who eat significantly less curry), Indians aged 70-79 develop AD one-fourth as often.

Although these data indicate that there is something special about Indian people with regard to AD, the many factors involved in the disease (which may involve a variety of things like genetics, exposure to certain toxins, eating things besides curry, etc.) make it inaccurate to state that curcumin is definitely the cause of India’s low prevalence of AD. However, the fact that curry (and thus, curcumin) is much more common in the Indian diet than the American diet does demonstrate what is called an inverse correlation between the use of curry and the prevalence of AD; that is to say, higher average amounts of curry intake are associated with lower prevalences of AD.

Having recognized this inverse correlation between curry and AD, scientists were able to take the research one step further. Interested in finding out whether or not curcumin might have a causal effect on combating AD, researchers turned to rodents (mice) as experimental animals in which to study the effect of curcumin on nerve cells. What they found in this research is discussed in the next section.

The Effects of Curcumin On the Cells of Rodents with Alzheimer’s^

The process through which Alzheimer’s disease degrades nerve cells is believed to involve three things: inflammation, oxidative damage, and most notably, the formation of beta-amyloid plaques. In order to understand how curcumin combats AD, we will look at its effects on each of these three phenomena.


On a short-term scale, inflammation is a very helpful event: it is the body’s way of protecting itself from foreign invaders. However, over an extended period of time, inflammation can actually be quite harmful. (For more info about inflammation, click here.) One of the ways that AD degrades nerve cells (and thus results in the manifestation of the disease’s symptoms) is by causing chronic inflammation in the central nervous system. For this reason, populations that exhibit prolonged use of certain nonsteroidal anti-inflammatory (NSAID) drugs like ibuprofen have been shown to have a reduced risk of developing the symptoms of AD. However, while ibuprofen significantly reduces the amount of inflammation in the central nervous system, its prolonged use has dangerous side effects like gastrointestinal, liver, and kidney damage.

Curcumin is a natural NSAID. For this reason, in mice models of AD, it was shown to reduce the levels of inflammation in the brain by about 60% (as measured by the reduced presence of a certain indicator of inflammation). An added benefit of curcumin is that it appears to be far less toxic than most drug NSAIDs. If further research confirms the safety of the substance, its use may become an alternative to drug NSAIDs for combating AD.

Oxidative Damage^

Like Huntington’s disease, AD can also increase the number of free radicals that nerve cells produce. Over time, this increased number of free radicals leads to oxidative damage, which can degrade nerve cells. In comparison to untreated mice with AD, mice with AD that were treated with curcumin had significantly reduced levels of free radicals. Thus, the oxidative damage that AD caused to the nerve cells of the curcumin mice was far less than the damage to the untreated mice.

Beta-Amyloid Plaques^

The most prominent characteristic in the brains of people with Alzheimer’s disease is the presence of beta-amyloid plaques. These plaques are basically an accumulation of small fibers called beta-amyloid fibrils. The plaques can be found in the spaces between nerve cells, and in addition to being a tell-tale sign of the disease, their presence is believed to contribute greatly to the neurodegenerative process of AD.

The levels of beta-amyloid in AD mice that were given low doses of curcumin were decreased by around 40% in comparison to those AD mice that were not treated with curcumin. In addition, low doses of curcumin also caused a 43% decrease in the so-called “plaque burden” that these beta-amyloids have on the brains of AD mice. Surprisingly, those AD mice that received high doses of curcumin did not show any decreases in beta-amyloid levels or plaque burden in comparison with untreated mice. While the exact reason for this finding is not yet clear, the results of it are intriguing: low doses of curcumin were actually more effective than high doses in combating the neurodegenerative process of AD.

How this Alzheimer’s Research May Affect Huntington’s Disease^

Although research to confirm such a notion is just now getting underway, the results of the Alzheimer’s study suggest that curcumin might well be helpful in combating other neurodegenerative diseases like HD. Despite the differences in the fundamental “cause” of each disease – HD is believed to be a purely genetic disorder, while AD is believed to have both genetic and environmental components – the damage to nerve cells in each disorder is strikingly similar. Thus, because curcumin combats the phenomena that contribute to neurodegeneration in AD, it is fair to suggest that the substance may possibly be capable of combating similar phenomena in HD.

Just as in Alzheimer’s, inflammation and oxidative damage play a strong role in the neurodegenerative process of HD: oxidative damage (also known as “oxidative stress”) helps to degrade nerve cells in the basal ganglia and cerebral cortex; chronic inflammation in the brains of people with HD is believed to play a significant role in the progression of the disease. ( For more info about inflammation, click here.) As shown previously, curcumin was able to reduce inflammation and oxidative damage in mouse models of AD. Although it is possible that the pattern of inflammation in the brain and the severity of oxidative damage may be different between AD and HD, if they are even slightly similar in the two disorders, then one would expect curcumin to also have a positive effect on combating HD.

Despite the harmful effects of inflammation and oxidative damage, beta-amyloid fibrils (which make up beta-amyloid plaques) have won the most attention among researchers and the general public with regard to AD. Similarly, despite the harmful effects of other phenomena that contribute to neurodegeneration, the most attention among researchers and the general public with regard to Huntington’s disease is devoted to huntingtin protein aggregation. The attention paid to beta-amyloid fibrils and huntingtin protein aggregation is not unjustified: in addition to being telltale signs of their respective disorders, these two phenomena may be key players in the neurodegenerative process. For instance, some researchers believe that substances which inhibit huntingtin protein aggregation will also be found to inhibit the initial structural alteration of the huntingtin protein, an alteration that is believed to start the entire disease process in HD. But there is another discovery that could have potentially profound effects on the research underway for both of these diseases: based on their ribbon-like structure and the mechanism by which they are created, huntingtin protein aggregates are quite similar to beta-amyloid fibrils. Given this discovery, it is possible that substances that decrease the presence of beta-amyloid fibrils may do the same with huntingtin protein aggregates, and vice-versa.

As of this writing (June 2004), research on the effectiveness of curcumin in combating huntingtin protein aggregation has just gotten underway. Should curcumin prove to decrease huntingtin protein aggregates as well as it did beta-amyloid plaques, this would be a true triumph in HD research. However, while this possibility is certainly a source of intrigue, it is important to note that not all substances that are proven to decrease beta-amyloid levels have shown the same effectiveness with huntingtin protein aggregation. For instance, the compounds thioflavine T, gossypol, melatonin, and rifampicin, all of which are believed to decrease the presence of beta-amyloid, had little or no success in inhibiting huntingtin protein aggregation. On the other hand, Congo Red and thioflavine S, which are also believed to decrease beta-amyloid, did effectively decrease huntingtin protein aggregation. Thus, while the similarities between beta-amyloid fibrils and huntingtin protein aggregates make us hopeful that curcumin can decrease the aggregates, current research on curcumin and HD will have the final say.

A closing remark: This section lacks definitive answers about how curcumin affects HD for one reason: the research simply has not yet been done. As the studies that are currently underway produce results, and as potentially more studies are begun, we will learn a great deal about how curcumin affects HD.

Uncertainties in How the Animal Research Relates to Humans^

The AD mice study mentioned in the above sections prompts us to offer some cautionary notes about directly applying results from mice to humans:

First, the AD study tested curcumin by splitting the mice into three groups: one group received a low dose of curcumin, another group received a high dose, and the third group received no curcumin at all. Curiously, comparing the low-dose group and high-dose group, low doses of curcumin actually appeared to combat neurodegeneration in AD better than high doses. While the reason for this finding is not yet fully understood, the results do tell us something important: just because a substance is helpful does not mean its helpfulness is increased with every increase in dosage. In fact, increased or prolonged dosages of an initially helpful substance can actually be harmful. In the ibuprofen study mentioned above, for example, gastrointestinal, liver, and kidney damage resulted from the prolonged use of otherwise helpful ibuprofen.

Second, it is also important to keep in mind that mice, of course, have significantly smaller bodies than humans and may metabolize substances differently than we do. Thus, despite its apparent safety in animal studies (for example, one study on mice used 83 times the normal amount of curcumin, and still produced no mortalities), one should always exercise caution when using a new substance (medicinal or natural) to treat a disorder. And as always, for advice about treating disease, it is important to consult a physician.

Clinical trials should soon be underway in order to establish the safety of using curcumin to combat AD in humans. If future laboratory and animal studies suggest that curcumin holds promise for combating Huntington’s disease as well, then clinical trials to test its safety and effectiveness in HD would also be needed.

For further reading^

  1. Heiser V, Scherzinger E, Boeddrich A, Nordhoff E, Lurz R, Schugardt N, Lehrach H, Wanker EE. Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: implications for Huntington’s disease therapy. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6739-44. PMID: 10829068 [PubMed - indexed for MEDLINE]
    A technical paper that describes the effectiveness of certain compounds in decreasing the amount of huntingtin protein aggregation in HD.
  2. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. . J Neurosci. 2001 Nov 1;21(21):8370-7. PMID: 11606625 [PubMed - indexed for MEDLINE]
    A technical paper that discusses how curcumin affects the nerve cells of Alzheimer’s mice. This is the paper on which the majority of the chapter was based.
  3. Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, Bates GP, Lehrach H, Wanker EE. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington’s disease pathology. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4604-9. PMID: 10200309 [PubMed - indexed for MEDLINE]
    A technical paper that discusses the similarities between huntingtin protein aggregates and beta-amyloid fibrils.

-M. Stenerson, 6-28-04


Cholesterol and Huntington's Disease




This chapter will investigate how cholesterol relates to HD. The chapter begins with a general overview of cholesterol and its role in the body. Following this, the chapter will focus on the cholesterol that originates in the brain, and on new research that looks at the relationship between cholesterol in the brain and HD.

What is cholesterol and what does it do?^

Cholesterol is a lipid molecule present in all animals. It is largely found in cell membranes, and there is a smaller amount circulating in the blood stream and stored inside cells. Cholesterol has a number of important functions. It is a key structural component of cell membranes, maintaining their fluidity and stability, and enabling important processes such as endocytosis. It is also important for the metabolism of fat-soluble vitamins, the manufacture of bile salts and the synthesis of vitamin D and steroid hormones. The synthesis of vitamins and hormones takes place in endocrine cells, while bile salts are generated in the liver.

Recently a small number of papers have shown that HD patients have altered levels of cholesterol in nerve cells. Since cholesterol plays a key role in the maintenance of healthy neurons, the disruption of normal cholesterol levels in HD patients may be a significant cause of neuron death and dysfunction.

Where does cholesterol come from?^

There are two major ways for our bodies to get cholesterol; it can be synthesized in the body, or obtained from the diet. Normally, our bodies take advantage of both methods of getting cholesterol. On average, a 150 pound person will synthesize about 1 gram of cholesterol per day and intake 200-300 milligrams through their diet.

The highest rate of cholesterol synthesis by the body occurs in the liver, although cholesterol is also made in the intestines, adrenal glands, CNS, and reproductive organs. Other cells can produce cholesterol, but typically in much lower amounts.

Cholesterol is found in all animal foods including meat, poultry, fish, seafood, eggs, and dairy. Cholesterol is not found in plants, so foods like fruits, vegetables, grains, nuts and seeds do not raise cholesterol levels. It is partly because we synthesize so much of our own cholesterol that excess dietary cholesterol is not necessary and can be harmful in a variety of ways.

In this chapter, our goal is to first provide a general review on cholesterol and its activity in the human body, and then look at its relationship to Huntington’s disease.

HDL and LDL^

Most people have heard of a distinction between two types of cholesterol: HDL and LDL. HDL stands for high-density lipoprotein, while LDL stands for low-density lipoprotein. HDL is commonly referred to as “good” cholesterol, while LDL is called “bad” cholesterol. More precisely, HDL and LDL are not simply different types of cholesterol, but rather alternative groups of lipids and proteins that transport the cholesterol throughout the body in the bloodstream. Molecules such as HDL and LDL are needed to carry cholesterol because it is a hydrophobic molecule and therefore cannot dissolve in blood and travel through the bloodstream on its own.

But if HDL and LDL are just alternative cholesterol carrier molecules, why is one considered good and the other bad? Medical studies have noted that high levels of LDL are associated with an increased risk of cardiovascular disease, whereas high levels of HDL are associated with decreased risk of cardiovascular disease.

How exactly does HDL produce beneficial effects and LDL produce harmful effects? LDL is the major cholesterol carrier in the blood and is responsible for delivering cholesterol to cells in the body. High levels of LDL cholesterol in the blood contribute to the formation of plaque. Plaque is a thick, hard deposit of fat, cholesterol and other substances that clogs arteries and causes atherosclerosis. If arteries become severely clogged with plaque, oxygen-carrying blood may not reach be able circulate around the body- which can lead to heart attack or stroke. Approximately one fourth of blood cholesterol is carried by HDL. HDL is believed to protect against atherosclerosis by carrying cholesterol away from the blood (so it cannot contribute to plaque formation) or even removing excess cholesterol from plaque already built-up in the arteries. HDL usually delivers cholesterol to the liver or endocrine cells, where it will be used in the synthesis of steroids or bile salts, and ultimately removed from the tissue and bloodstream.

Cholesterol as a Risk Factor for Heart Disease^

When our cholesterol levels are tested, they are shown in milligrams per deciliter of blood (mg/dL). The American Heart Association classifies anyone with total cholesterol greater than or equal to 240 mg/dL as belonging to a high risk category. They recommend that those with a total cholesterol level in this high range get a complete fasting lipoprotein profile done. This test measures LDL, HDL, and triglyceride levels. Triglycerides are another contributor to atherosclerosis. The target HDL level is greater than 40 mg/dL, the target triglyceride level is less than 150 mg/dL, and the target total cholesterol level is less than 240 mg/dL.

Cholesterol and Triglyceride Levels (mg/dL)

Optimal Near Optimal Borderline High High Very High
Total Blood Cholesterol <200 —- 200-239 =240 —-
LDL Cholesterol <100 100-129 130-159 160-189 =190
Triglyceride Level <150 —- 150-199 200-499 =500

*Information from the American Heart Association

There are several ways to lower cholesterol levels that are too high. The best methods are usually lifestyle changes. These can include dietary changes such as eliminating foods that are high in saturated fat, trans fat, and cholesterol and increasing the consumption of fruits, vegetables and grains. Exercise is also an important way to reducing the amount of cholesterol in our bodies. By exercising for 20-30 minutes each day we use up greater amounts of fats and other energy molecules that are stored in our bodies. Additionally, there are medications that help lower cholesterol. These medications usually employ one of two general strategies. They either block the synthesis of cholesterol within the bodies’ cells or they prevent cholesterol uptake in the intestine, forcing ingested cholesterol to pass through the body and never be absorbed. The best way to stay healthy is to make sure you have had your cholesterol tested and, if it is too high, to follow your doctor’s instructions for lowering it.

Cholesterol in the CNS^

The CNS contains a large amount of cholesterol, as cholesterol is needed for the growth and maintenance of myelin, as well as neuron and glial cell membranes and for the formation of new connections between cells. However, the CNS is unique in that there is no evidence that it obtains any of its cholesterol from the blood. Instead, cells in the CNS synthesize all of their own cholesterol. In fact, the rate of cholesterol synthesis in the CNS exceeds the need for new cholesterol, so that some cholesterol must move out of the CNS through excretory pathways.

It is not easy for molecules to enter the CNS. Tightly joined endothelial cells found in the capillary network within the brain prevent many molecules from moving from the blood to the CNS. This blood-brain barrier makes it unlikely that cholesterol carried in lipoproteins could reach the CNS unless there were specific transporters in the endothelial cells of the vessel walls. Currently there is no evidence that existing transporters in those endothelial cells actively uptake lipoprotein-transported cholesterol.

Relating cholesterol to Huntington’s disease^

A few studies have recently investigated the role of cholesterol in HD and have suggested that HD may disrupt the normal cholesterol homeostasis in the brain. These research articles propose that the altered huntingtin protein may cause a change in intracellular levels of cholesterol in neurons by disrupting at least two cellular mechanisms: endocytosis and cholesterol biosynthesis. Ultimately, these cellular changes may lead to dysfunction or death of the striatal neurons and reflect another pathway or mechanism by which the mutated huntingtin protein affects the cell and causes neurodegeneration.

Cholesterol Accumulation and Inhibited Endocytosis^

A study by Trushina et al. has reported that the mutant huntingtin protein inhibits a specific type of endocytosis in striatal neurons. These neurons are also shown to have strikingly high intracellular levels of cholesterol.

Mutant huntingtin has been previously shown to interact with clathrin, which is a major protein involved in endocytosis. In this study however, a different protein has been implicated in the disruption of endocytosis in HD. It has been demonstrated that the mutant huntingtin protein interacts with the protein caveolin-1 (cav1), a key molecule in a different endocytotic pathway (called caveolar-related endocytosis). The interaction of mutant huntingtin protein and cav1 inhibits caveolar-related endocytosis and also causes an accumulation of cholesterol within neurons.

Examination of mouse tissue and HD striatal cell cultures revealed the accumulation of intracellular cholesterol. Researchers found that using siRNA to knockdown cav1 translation prevents cholesterol accumulation. For more on siRNA techniques, click here. This occurred only in the continued presence of mutant huntingtin protein, suggesting that it is something specifically about the nature of the interaction between altered huntingtin and cav1 that disrupts normal cholesterol homeostasis, and not simply the lack of cav1 altogether. It was also observed that in all cases clathrin-dependent endocytosis was normal, indicating that the mechanism of cholesterol accumulation was specific to the disruption of the caveolar-related pathway.

How is cholesterol biosynthesis affected?^

In another recent paper, by Valenza et al., Huntington’s disease has been shown to decrease cholesterol biosynthesis in nerve cells. The presence of altered huntingtin in these cells is correlated with significantly lower total cholesterol mass. This was observed in mouse tissue and in cultured striatal neurons expressing a fragment of the mutant huntingtin protein.

Mutant huntingtin affects the transcription of genes crucial to cholesterol synthesis. The altered huntingtin protein interacts with binding proteins called sterol regulatory element -binding proteins (SREBPs) and prevents these proteins from entering the nucleus. These proteins usually bind to DNA and promote transcription of many different genes important for synthesizing cholesterol. Mutant huntingtin has a strong effect on SREBPs; the proteins are reduced by 50% in the nucleus of HD cells. Reduction of the SREBPs results in significantly less transcription of the genes involved in cholesterol biosynthesis, which ultimately reduces total cholesterol.

Large changes in the levels of intracellular cholesterol will eventually lead to disruption of cellular homeostasis. Research with HD cell line models has shown that the addition of exogenous cholesterol to cultured striatal neurons expressing mutant huntingtin joined to a green fluorescent protein will prevent these neurons from dying.


Cholesterol is essential for promoting synapse formation and maintaining membrane integrity in CNS neurons. It is also a major component of myelin and important for optimal neurotransmitter release. Because cholesterol plays such a major role in CNS growth, development, and maintenance, disruptions of cholesterol homeostasis can have negative consequences. Accumulation and depletion of intracellular cholesterol in neurons are both possible mechanisms contributing to neuron dysfunction in these HD models. However, the findings are limited to HD cell models and postmortem HD tissue. This work now needs to be followed up by investigating these changes in HD patients to see whether similar dysfunction occurs.

If studies in human subjects found a similar dysfunction in cholesterol homeostasis, it might suggest that adjusting the cholesterol levels in neuronal cells could be a potential treatment for HD. Future research may aim to discover how to transport cholesterol across the blood brain barrier and whether cholesterol therapy could be one way of slowing or halting neuronal cell death in HD.

It is interesting to note that similar defects in caveolar-related endocytotic pathways and perturbations of cholesterol homeostasis have been implicated in other neurodegenerative diseases related to HD like Alzheimer’s disease and Parkinson’s disease.


Recent research has suggested that disruptions in cholesterol homeostasis could be important in explaining how the HD mutation causes neurodegeneration. However, cholesterol’s role in the disease is still not fully understood. It might seem strange that HD has been linked to both intracellular cholesterol accumulation and depletion. One current hypothesis is that different stages of the disease are characterized by different disruptions to cholesterol homeostasis. Future research should shed light on the connections between these different disruptions and normal cholesterol activity.

For Further Reading^

-A. Hepworth, 5/13/2007


Complications of Huntington's Disease

Huntington’s Disease (HD) is not fatal in itself. People with HD have a shorter life expectancy and die of other life-threatening complications related to this disease. Pneumonia and heart disease are the two leading causes of death for people with HD. Additionally, HD patients have higher incidence of choking and respiratory complications, gastrointestinal diseases (such as cancer of the pancreas), and suicide than the non-HD population. Why are HD patients more prone to the above complications than the rest of the population? This chapter aims to answer that question and draw connections between the symptoms of HD and the most common causes of death (see the table below). Although researchers have not explicitly proven these links in every case, the following information hopes to demonstrate a logical connection.

Primary cause of death (in rank order) Persons (total=182) Percentage
Other respiratory diseases
Myocardial infarction/degeneration (heart attack
Congestive cardiac failure (heart failure)
coronary disease
Other diseases of the cardiovascular system
Unspecified Huntington’s-related causes 23 12.6
Vascular lesions of central nervous system 10 5.5
Non-vascular lesions of central nervous system (e.g. meningitis) 4 2.2
Genito-urinary diseases (e.g. kidney failure) 5 2.7
Gastro-intestinal diseases (cancer of the pancreas) 3 1.6
Suicide 3 1.6
Reed TE, Chandler JH, Hughes EM, et al. Huntington’s chorea in Michigan: I. Demography and Genetics. Am J Hum Gen 1958; 10: 201-225.

One of the chief symptoms of HD is the inability to produce coordinated movements. In the latter stages of the disease, this problem becomes more pronounced to the point that people have difficulty swallowing. Although it is so common that we hardly think about it, swallowing is actually a complex series of movements by muscles in our throat to ensure passage of food into the esophagus (gastrointestinal tract) rather than the trachea (respiratory tract). As a result of these movements, the epiglottis, a flap that acts as a valve in our throat, prevents food from entering the airway. People with HD often lack this coordination, and food will accidentally enter the respiratory tract, leading to choking. Moreover, when food particles manage to get into the trachea (the “wind pipe” leading to the lungs), instead of the esophagus (the “food pipe” leading to the stomach), the lungs can become infected and cause what is known as aspiration pneumonia.

Although pneumonia is relatively common among people in the general population, it is only fatal in about 5% of these cases. However, pneumonia is much more dangerous in people with compromised immune systems. Researchers have demonstrated that stresses imposed on a person for prolonged periods of time can severely damage the body’s ability to ward off diseases. The physical, cognitive, and psychiatric symptoms of HD add a great deal of stress to everyday life for these patients (for more information on these symptoms, click here). As a result, their immune systems are compromised and diseases such as pneumonia are therefore more likely to result in death. For instance, in a long-term study conducted from 1952 until 1979 in Victoria, Australia, researchers found that more than 51% of patients with HD died from pneumonia.

The increased physical and emotional stress associated with HD can cause other problems as well. Chronic stress has been linked to high blood pressure, increased risks for heart attacks, and tumor growth. In addition, although studies have shown that suicide is not a leading cause of death for HD patients, suicide rates are higher than among the rest of the population. This is probably due to a combination of factors, including neuropsychiatric changes induced by HD and the added stress of daily life.

Although researchers have yet to find a cure for the disease, people with HD can take measures to prolong their lives. For example, extra care should be taken when eating to prevent choking and pneumonia caused by food going the wrong way. Regular exercise and sleeping in an elevated position can reduce the risk of respiratory infections. Patients can also maintain a healthy diet and reduce or eliminate other risk factors for heart disease, such as smoking and alcohol, from their lives.


Couple Relationships and Huntington's Disease Testing

Huntington’s disease presents unique psychosocial issues due to its late onset and hereditary nature. One of the major issues of course is stress, which can come from many sources and has many effects (for general discussion of stress and HD, click here. A major source of psychosocial stress associated with HD comes from predictive testing which became available in the United States in 1993.

Extensive research has focused on the person undergoing predictive testing, with a good number of studies reporting that the tested person’s benefit from the knowledge of their genetic status outweighed their post-test psychosocial distress. However, less research has focused on the psychological impact that predictive testing may have on those at risk for HD and their partners, family and friends. This research is important because HD affects many more people than just the person who has it. Moreover, the hereditary nature of the disease can also lead to difficult questions about reproduction and about the possibility of other family members having the disease.

Fortunately, researchers are now focusing more of their attention on predictive testing and its effects on the couple relationship. In the remainder of this section, we review their key findings to date.

What percentage of couples looks favorably upon predictive testing? And what motivations drive their decisions?

In a 1989 study in Belgium, where HD predictive testing has been available since 1987, Evers-Kiebooms found that a moderate majority of people at-risk for HD and their non-carrier partners looked positively on predictive testing. Out of 349 study subjects, 66% of the at-risk adults and 74% of their partners wanted testing for the at-risk individual. The difference between these percentages can partly be explained by the difference in motivations between the at-risk person and his/her partner in approving the predictive testing. When asked why they approved, at-risk adults tended to cite worries about their futures, while their partners tended to cite worries about current and/or future children. A reason that some couples decided not to undergo predictive testing was concern about the effects of the testing on their relationship; this concern was more often a major consideration for non-carrier partners than for the at-risk adults. (For specifics on the process of HD predictive testing, please click here.

Is there a theory on how predictive testing affects couple relationships?^

Yes, a perspective called family systems theory, developed over the past few decades, has proven particularly useful in genetic counseling. This theory is especially relevant to the genetic counseling of couple relationships because its central focus is on the family rather than the individual. The family systems theory describes human behavior as a consequence of family relationship patterns, rather than individual psychology. Consequently, family systems theory can help explain the effects of predictive testing on couple relationships by analyzing how family relationship patterns can influence post-test behavior.

In a 2004 study by Richards and Williams, 43 couples were divided into two groups: those that chose to undergo predictive testing and those that chose not to. Couples in both groups answered the same questionnaire before predictive testing, then 6 months later (3 months after those tested received their test results), and again 24 months after the first questionnaire. The questionnaire consisted of 32 Dyadic Adjustment Scale questions that measured couple relationship functioning, known as a “couple score.” Those couples that received higher couple scores frequently interacted and communicated with each other, rarely disagreed with each other on significant marital issues, and settled disagreements in a way that was satisfying to both partners.

The major finding of this study was that, over the 24 month period, there was no statistically significant difference in couple scores between couples who had decided to undergo predictive testing and couples who had decided not to. The key conclusion was that predictive testing has few negative effects on couple relationships. As the authors noted, this conclusion matches the findings of several other studies (Tibben et al., 1993a; Cordori and Brandt, 1994; Quaid and Wesson, 1995; Taylor and Myers, 1997. For a look at these studies, please see “For Further Reading” at the end of this chapter).

An additional finding from the 2004 study is interesting. The couples that underwent predictive testing were categorized into couples in which the at-risk partner was a carrier and couples in which the at-risk partner was a non-carrier. Unexpectedly, the carrier couples had higher couple scores (stronger couple relationships) of statistical significance than the non-carrier couples. This suggests that, for some couples, the knowledge that their at-risk partner did not have HD had a greater negative effect on their marital relationship than the knowledge that their partner did have HD. The authors give a possible explanation: “The threat of HD may have served as a factor in the continuance of the relationship. Once this threat is removed, partners may no longer feel a duty or need to remain in the marriage to care or to be cared for.”

Another possible explanation is provided by examining family patterns via family systems theory rather than individual behavior. Family systems theory suggests that the couple relationship can be negatively affected when one or both partners have different expectations for the predictive test’s results. When the results prove to be different from expectations, conflict can arise contributing to relationship deterioration and lower couple scores. Studies by Huggins et al. and Soldan et al. have found that professional genetic counseling can benefit the couple relationship by helping partners discuss their expectations of the predictive test’s results and their coping strategies (See “Further Reading” below for links to these two studies).

What does the medical literature say about the pros and cons of predictive testing for couple relationships, especially psychosocial aspects?^

Similar to the work of Richards and Williams reviewed above, a study by Decruyenaere in 2004 also used the Dyadic Adjustment Scale to measure changes in the couple relationship for 5 years following predictive testing. But the study also collected qualitative data from separate interviews with the at-risk persons and their partners. Qualitative data are useful because they can provide more thorough explanations for trends observed in couple relationship over time. The specific couple relationship examined in the Decruyenaere study was marriage.

In this study, all at-risk persons were undergoing predictive testing, with 26 carriers and 14 of their partners, and 33 of non-carriers and 17 of their partners participating in the study. The main finding was that the majority (70%) of the tested persons did not have a change in marital status over the 5 years of the study. As for the quality of the marital relationship, half of the couples reported no change in that interval compared to the quality before the predictive testing. Out of those that did report change, non-carrier couples cited less distress and more communication. Carrier couples that experienced increased relationship quality over the five years cited more mutual support.

A conclusion that can be drawn from this study is that the test result does not by itself predict outcomes in the couple relationship; even couples with negative test results for HD may experience post-test psychosocial distress and couple relationship breakdown. The important factor for couples undergoing predictive testing is whether the test result causes role shifts that upset the balance of the pre-test couple relationship. For example, two couples that received positive test results reported frustration as the partners shifted toward caretaking roles even before the people with HD showed any symptoms. In another couple tested, a woman believed to be at risk for HD gained self-esteem from a negative result. With low self-esteem before the test, she had married someone who did not match her ideals in a spouse. After the testing showed she did not have HD, she regretted her decision to marry her husband, clearly leading to relationship deterioration.

Since undesired shifts in roles may contribute to couple relationship breakdown whether the test result is positive or negative, the researchers of this study strongly support post-test counseling. Post-test counseling can help couples find and maintain a new balance that is satisfying to both partners. This counseling should include open communication between the partners, with special attention paid to the desires and worries of each partner.


It is clear from these studies that the psychosocial impact of predictive testing on the couple relationship is complex, with a number of factors that contribute to both positive and negative outcomes. First, the Richards and Williams study shows that pre-test discussion by the couple can be very helpful to their relationship. Such discussion can better prepare the couple for the test result by encouraging understanding of each other’s expectations of and reactions to the test result. In particular, this pre-test assessment can help identify particular challenges that the couple may face after the testing and may lead to re-consideration of testing in the first place. Complementing the Richards and Williams study, the Decruyenaere study shows the importance of post-test counseling. Post-test counseling can help protect against adverse effects of predictive testing by encouraging open discussion of each partner’s concerns as well as identification of any potential role-shifts that may disrupt the couple relationship.

Further Reading^

  • Decruyenaere M, Evers-Kiebooms G, Cloostermans T, Boogaerts A, Demyttenaere K, Dom R, Fryns JP. Predictive testing for Huntington’s disease: relationship with partners after testing. Clinical Genetics. 2004 Jan;65(1):24-31.
    This study is not only easy-to-read but also optimistic in its finding that most marital relationships remained the same five years after predictive testing, regardless of the test results.
  • Evers-Kiebooms G, Swerts A, Cassiman JJ, Van den Berghe H. The motivation of at-risk individuals and their partners in deciding for or against predictive testing for Huntington’s disease . Clinical Genetics. 1989 Jan;35(1):29-40.
    This early study found that the majority of at-risk persons and their partners looked favorably upon predictive testing, although the at-risk individual and his/her partner’s reasons for deciding to take the test varied. This study took place before predictive testing began in 1993; however, the couples’ explanations for deciding on predictive testing are still eye-opening and relevant.
  • Huggins et al. Predictive testing for Huntington disease in Canada : Adverse effects and unexpected results in those receiving a decreased risk . 1992 Am J Med Genet 42:508-515.
  • Richards F, and Williams K. Impact on couple relationships of predictive testing for Huntington disease: a longitudinal study. American Journal of Medical Genetics Part A. 2004 Apr 15;126(2):161-9.
    This is an easy-to-read article that is especially interesting because of its discussion on the benefits of pre- and post-test counseling.
  • Soldan et al. Psychological model for presymptomatic test interviews: Lessons learned from Huntington disease . 2000 J Genet Couns 9:15-31.

Studies, in addition to Richards and Williams 2004, that found few negative effects of predictive testing on couple relationships:

  • Codori AM, et al. Psychological costs and benefits of predictive testing for Huntington’s disease. 1994 Am J Med Genet 54:174-184.
  • Quaid KA, et al. Exploration of the effects of predictive testing for Huntington disease on intimate relationships. 1995 Am J Med Genet 57:46-51.
  • Taylor CA, et al. Long-term impact of Huntington disease linkage testing . 1997 Am J Med Genet 70:365-370.
  • Tibben A, et al. On attitudes and appreciation 6 months after predictive DNA testing for Huntington disease in the Dutch program . 1993 Am J Med Genet 48:103-111.

-C. A. Chen 5-7-07