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Stages of Huntington’s Disease

Stages-of-HD

People with Huntington’s disease (HD) follow a path of disease progression once symptoms begin. While patients can remain highly functional in the first years of the disease, independence gives way as symptoms get worse. This article discusses the ways in which HD symptoms change from one stage to the next, the degree to which individuals are independent in day-to-day life at each stage, and some common concerns along the way.

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The Motor Symptoms of Huntington’s Disease

Huntington’s disease (HD), an inherited neurodegenerative disorder, damages specific areas of the brain, resulting in movement difficulties as well as cognitive and behavioral changes. HD is often characterized by the motor symptoms that it causes.

Huntington’s disease (HD), an inherited neurodegenerative disorder, damages specific areas of the brain, resulting in movement difficulties as well as cognitive and behavioral changes. HD is often characterized by the motor symptoms that it causes. In fact, when HD was first discovered it was called Huntington’s chorea, as a reference to the uncontrollable, dance-like movement that is common among people with HD. Motor symptoms, though not always the first symptoms to appear, are often the reason that people with HD first see a doctor. Before genetic testing for the expanded CAG repeat within the Huntington gene became available, doctors could only make diagnoses according to motor symptoms. Even today, these symptoms are an important part of the criteria for clinical diagnosis; they generally define the age of onset of HD in an individual.

marker control range basic inhibition oxygen neurotrophic factor

What are the motor symptoms that occur with HD?^

The progression of HD is different in every individual, but the following list contains most of the physical conditions that occur frequently in adult-onset HD. Keep in mind that not everyone with HD will experience all symptoms, and the progression from stage to stage is only a generalization. The time it takes to move from one stage to the next is also highly variable. It is important to note as well that juvenile HD exhibits motor symptoms that can be quite different from the adult form. (For more information on juvenile HD, click here).

Early stage^

  • Changes in coordination
  • Some involuntary movement (such as irregular, sudden jerks of limbs)
  • Fidgeting
  • Restlessness, desire to move about
  • Twitching, muscle spasms, tics
  • Less control over handwriting
  • Facial grimaces
  • Difficulty with coordinated activities, such as driving
  • Some rigidity

Middle Stage^

  • Dystonia (prolonged muscle contractions), often of the face, neck, and back
  • More involuntary movements
  • Trouble with balance and walking
  • Chorea, twisting and writhing motions, jerks
  • Staggering, swaying, disjointed gait (can seem like intoxication)
  • Speech difficulties, including poor articulation, grunting, and abnormal speech patterns
  • Problems swallowing
  • Trouble with activities that require manual dexterity
  • Slow voluntary movements, difficulty initiating movement
  • Inability to control speed and force of movement
  • Slow reaction time
  • General weakness

Late Stage^

  • Rigidity
  • Bradykinesia (difficulty initiating and continuing movements)
  • Severe chorea (less common)
  • Serious weight loss
  • Inability to walk
  • Inability to speak
  • Swallowing problems, which create danger of choking
  • Inability to care for oneself

Though HD is not fatal in and of itself, the conditions that it causes can eventually lead to death. One of the most serious concerns for people with late stage HD is loss of control of the throat muscles. This condition makes swallowing difficult, and ultimately, dangerous. Everyone’s body is constructed with two tubes that begin below the throat; one, the esophagus, leads to the stomach, and the other, the trachea, leads to the lungs. Usually, we have no trouble making sure that food passes through our esophagus and not into our trachea. We do this without thinking, and rarely does something go “down the wrong pipe.” For people with late stage HD, however, this process of sorting food and air often functions poorly. As a result, food can get caught in the trachea and lead to choking. If food gets caught in the lungs, it can lead to an infection known as aspiration pneumonia. Although most people recover from pneumonia, people with HD usually have compromised immune systems, and therefore are unlikely to recover from such a severe infection. (For more information on other potential complications of HD, click here.

If you would like to learn more about the specifics of motor symptoms and how they are used to diagnose and assess the stage of HD, click here).

What exactly is chorea?^

Chorea is a disorder of the nervous system that occurs in multiple clinical conditions. In other words, it is not limited to HD, even though it is one of the classic symptoms associated with this particular disease. Chorea is characterized by spontaneous, uncontrollable, irregular movements, generally of the limbs and face. It can appear as unexpected jerks or twisting, writhing motions. These unpredictable movements contribute to poor balance, and the resulting walking difficulties lead to the staggering, swaying gait associated with HD. It is this irregular walking pattern that can make people with HD appear intoxicated, and also explains the root of the word chorea, which is the Greek word for dance. In the extreme, chorea can be a constant stream of violent movement. Severe choreic motions are known as ballismus.

Chorea occurs in 90% of people with HD, and increases over the first 10 years following onset. Although the specific motions of chorea can vary from one individual to the next, there are often consistent patterns within individuals. Chorea is usually present during waking hours, and cannot generally be suppressed. As HD progresses, chorea normally gives way to other movement difficulties, such as rigidity and bradykinesia.

To view a video clip showing chorea, please here. Footage is from Lake Maracaibo, Venezuela, courtesy of Dr. Nancy Wexler. HOPES would like to thank Julie Porter and the HD Foundation as well.

How can motor symptoms be treated?^

Unfortunately, as there is no cure for HD, there is also no cure for the motor symptoms that accompany the disease. There are, however, drugs and supplements available that may lessen certain motor symptoms of HD. It is also possible to treat many of the behavioral symptoms, which can greatly improve quality of life. (For more information on drugs and supplements that are used to treat HD, click here, and for information about behavioral symptoms, click here). Under certain circumstances, there is a surgical procedure that can be performed, which involves making stereotactic lesions in a part of the brain called the thalamus. This procedure may alleviate motor symptoms, but it can only be performed when no cognitive decline is evident, and ultimately it does not halt the progression of the disease. (For more information, please visit the UCLA Medical Center website by clicking here).

In addition to clinical treatments, there are other means of dealing with motor difficulties. One place to start is with health professionals: speech pathologists, physical therapists, and occupational therapists. Speech pathologists help with the mechanics of eating and drinking, as well as the loudness and articulation of speech. They can provide strategies for improving communication within the family and can also begin discussions about the use of a feeding tube, in the event that such a step becomes necessary. Exercise can be a very positive means of therapy, with physical, psychological, and emotional benefits. Physical therapists develop specialized exercise programs, usually to improve stretching and range of motion. They also advise people with HD about the use of walkers and wheelchairs. (For more information on exercise and HD, click here). Occupational therapists find ways to help people compensate for their inability to perform daily tasks, like eating and dressing. Often this involves adjusting the surrounding environment to better suit the needs of the individual with HD. Even small changes can make him or her feel more comfortable and capable, and thereby make his or her symptoms less problematic in daily life. (For suggestions on environmental adjustments, click here).

Motor symptoms can also be managed through lifestyle adjustments. Exercise, as previously mentioned, diet, and stress all affect overall health, and may contribute to the severity of symptoms. You should always consult your doctor before making any changes to your normal routine, but by clicking here, you can learn more about lifestyle adjustments that could potentially have positive effects.

What causes motor symptoms?^

The reasons why HD causes motor symptoms are very complex and not entirely clear. However, researchers have learned a great deal about what may be at the root of the problem. In order to begin discussing why motor symptoms occur, we first have to look at how movement is organized in the brain. Motor control operates through two main pathways, which link the cortex (the outer part of the brain, responsible for sophisticated functions) with the basal ganglia (a grouping of cells found deep within the brain, responsible for more basic functions). These pathways are termed “direct” and “indirect.” Before continuing, you may want to take a moment to review these two pathways described here, in the Neurobiology of HD section.

After reviewing the basics of the direct and indirect motor pathways, we can examine this schematic diagram that combines the two (Figure 1). Notice that there is an additional pathway: nerve cells in the striatum also project, or link, onto a region of the basal ganglia called the substantia nigra (as well as the globus pallidus), which then projects directly back onto the striatum. Though it may seem odd to have a simple loop added to this system, we will see that this pathway, the striatonigral pathway, is very important to motor function.

Fig MS-1: Motor pathways

In looking at the diagram, notice that along each projection arrow there is the name of a particular chemical, known as a neurotransmitter. Neurotransmitters are the means by which cells (and brain regions) communicate with each other. One cell, the presynaptic cell, releases a neurotransmitter and another cell, the postsynaptic cell, absorbs it. This chemical signal causes the postsynaptic cell to take some sort of action, such as releasing a neurotransmitter or actively not releasing one. Its response will then influence other cells farther down the line. This progression of cell-to-cell chemical communication is the nuts and bolts of the motor control pathways that we have been discussing.

You can see from the diagram that each motor pathway involves a complex combination of neurotransmitters. Let’s walk through the various pathways to get a clearer picture of how this all works. Remember though, it is the overall concept of the pathways that is important, not the names of each brain region and neurotransmitter.

The first step for all motor pathways is the cortex receiving sensory information from the outside world, via sight, touch, hearing, etc. It transmits this information to the striatum (part of the basal ganglia) in chemical form, using a common neurotransmitter called glutamate. Glutamate then causes the cells of the striatum to take action in the following ways:

The direct pathway: Nerve cells in the striatum project onto the internal part of the globus pallidus, using the neurotransmitters GABA and substance P. The cells of the globus pallidus then use GABA in their projections to the thalamus, a major relay and control center of the brain. The thalamus completes the loop back to the cortex using more neurotransmitters, sending its signals directly to the part of the cortex devoted to motor control, the motor cortex. The motor cortex responds to these signals (which originated in the basal ganglia, remember) by physically moving the body in the appropriate way.

The indirect pathway: Striatal cells (cells in the striatum) use GABA and enkephalin to project onto the outer part of the globus pallidus. Globus pallidus cells then project to the subthalamus using GABA, which in turn projects to the internal globus pallidus using glutamate. From there the pathway is the same as the direct pathway, progressing to the thalamus and then the motor cortex.

An important note: Certain neurotransmitters are termed “excitatory” and others “inhibitory.” Excitatory neurotransmitters cause an action to take place in another cell or part of the body. Inhibitory neurotransmitters prevent an action from occurring. All projections that come from the basal ganglia (including the striatum, globus pallidus, and substantia nigra) are inhibitory. We know that these cells are involved in controlling the movement of the body, so therefore the neurotransmitters from cells in the basal ganglia serve to prevent (or inhibit) movement. Imagine you are sitting at a desk, writing on a piece of paper. You are moving your hand and arm, but the rest of your body is still. In order to keep the rest of your body still, the cells in your basal ganglia are releasing inhibitory neurotransmitters constantly. In this state, cells are said to be operating at their baseline firing rate. “Baseline” refers to what is normal, because most of the time we want to prevent movement in at least some parts of our body, and “firing rate” refers to how frequently the neurotransmitters are released. Consider that while you are at the desk writing, you see that you have made a mistake. This visual sensory information reaches your cortex, and then is sent to your basal ganglia. The basal ganglia realize that you will need to tell your other arm to reach for an eraser. In order to stop inhibiting movement in that arm, the basal ganglia must adjust its release of inhibitory neurotransmitters. This modified signal is passed to the thalamus and then the motor cortex. Because the motor cortex is no longer inhibited as much, it can tell your other arm to reach for the eraser. When you have finished using that arm, neurotransmitter release returns to normal, to the baseline firing rate.

How does all this work in HD? Mutant huntingtin protein is expressed in all the cells of the body, but the most and earliest damage is seen in the basal ganglia, and the striatum in particular. The precise mechanism by which mutant huntingtin harms cells and causes them to behave differently is not clear. However, we know that mutant huntingtin causes serious problems with cell function and eventually leads to cell death. Here is where an understanding of motor pathways comes in handy. The early motor symptoms seen in HD are the result of damage to the striatum that impacts the indirect pathway (although both pathways are affected at the same time in juvenile HD). Damage from HD causes the striatum to release a weaker chemical signal, resulting in less inhibitory neurotransmitters, less inhibition of the motor cortex, and more movement. This movement is unintended, the result of a pathway error, and is therefore called “involuntary.” Involuntary movements include the fidgeting, tics, and chorea associated with early to middle stage HD. Later on in the disease the direct pathway becomes increasingly affected. In this case, the striatum still releases less inhibitory neurotransmitters, but in the direct pathway this action leads to more inhibition of the motor cortex and less movement. The result is rigidity of the body and bradykinesia, common to late stage HD. So, looking at how the direct and indirect motor pathways work and the motor symptoms we know to occur in HD, we can follow a logical route from damage in the striatum to actual symptoms. But what causes the neurotransmitter signals from the striatum to decrease in the first place? Let’s first take a look at the third motor pathway in the diagram.

Fig MS-2: Third motor</p> <p>pathway

The striatonigral pathway: Nerve cells in the striatum also project onto the substantia nigra, using GABA. The substantia nigra then responds with dopamine, projecting straight back onto the striatum. This dopamine signal influences both the direct and indirect pathways, but with different results, even though both pathways are responding to the same chemical signal. This is accomplished by having two different kinds of dopamine receptors on the post-synaptic cells in the striatum: D1 receptors link to the direct pathway and D2 receptors link to the indirect. Dopamine that goes to D1 receptors causes the striatum to release less inhibitory neurotransmitters, which ripples through the whole direct pathway and ultimately leads to inhibition of the motor cortex (preventing movement). Dopamine that goes to D2 receptors also causes the striatum to release less inhibitory neurotransmitters, but because of a different pathway progression, ultimately leads to less inhibition of the motor cortex (causing movement).

Fig MS-3

Researchers think that the answer to why HD causes the striatum to release a weaker chemical signal may be the striatonigral pathway and dopamine. As we have discussed, HD seems to over-stimulate the motor cortex via the indirect pathway and under-stimulate the motor cortex via the direct pathway. Interestingly, this pattern matches up with the influence of the striatonigral pathway on the other two pathways. When dopamine is released from the substantia nigra, it inhibits the striatum, causing it to release less inhibitory neurotransmitters. Let’s put these ideas together: if an excess of dopamine is released from the substantia nigra, the indirect pathway would over-stimulate the motor cortex and the direct pathway would under-stimulate it, just like in HD. You can see why researchers started to think that the striatonigral pathway and dopamine might be the key.

Fig MS-4

So what causes the substantia nigra to release more dopamine? For a potential answer we must trace the pathway back even further. Remember that as soon as the striatum receives a sensory message from the cortex, it sends a signal to the substantia nigra, via the neurotransmitter GABA, which then influences the substantia nigra’s release of dopamine. These two neurotransmitters go back and forth like a seesaw: more GABA means less dopamine and vice versa. Researchers have found that cells in the striatum that release GABA selectively degenerate due to damage from mutant huntingtin. GABA is an inhibitory neurotransmitter like all those in the basal ganglia. Therefore, if striatal cells are damaged and release less GABA, the substantia nigra is less inhibited and will release more dopamine. An increase in dopamine would inhibit the striatum, which is consistent with the pattern seen in HD.

It is important to note, however, that scientific studies have not been able to show conclusively that dopamine levels are increased in HD. Indeed, post-mortem studies of people with HD have shown elevated, depleted, and unchanged levels of dopamine in the brain. Additionally, the striatum uses GABA in its projections to both parts of the globus pallidus, not just the substantia nigra. Therefore, damage to the striatum from HD could lessen the release of GABA to the globus pallidus and thus the two main pathways directly, not just via the striatonigral pathway.

Nonetheless, many researchers are confident that dopamine is important to HD, even at endogenous, or natural, levels. Dopamine may in fact play an even more integral role in striatal cell damage, by causing the damage, not just influencing the pathway. One major question for researchers has been, why the striatum? Why is the basal ganglia harmed by mutant huntingtin, and not other cells? Recent studies suggest that the presence of dopamine is correlated with cell damage in HD. If this is the case, only cells in which dopamine was present would degenerate, and those with more dopamine would degenerate first. This theory would explain why cells in the striatum degenerate first. Charvin and others (2005) have shown that both dopamine and mutant huntingtin can activate a transcription factor known as c-jun. Transcription factors can influence a cell in many different ways; c-jun leads to programmed cell death, or apoptosis. When dopamine and mutant huntingtin are present together, the level of c-jun is greatly increased. The way that dopamine activates c-jun is as follows: dopamine can autooxidize, or in other words, spontaneously undergo a reaction that leads to reactive oxygen species (ROS). ROS are bad for the cell, and usually lead to cell damage. To prevent this damaged cell from hurting the rest of the body, the cell activates c-jun to start the process of programmed cell death (apoptosis). Therefore, the apoptosis of one cell is a good defense mechanism for the body. When mutant huntingtin is present, however, far too many cells induce apoptosis. Also, as we age, autooxidation of dopamine naturally increases. You can imagine that in someone with HD, more and more apoptosis due to dopamine combined with the presence of mutant huntingtin, could result in significant problems. This theory may therefore explain HD’s late age of onset. (For more information about the theory of oxidative stress and HD, click here).

Charvin and others proposed another role for dopamine in striatal cell damage. As previously mentioned, there are two kinds of dopamine receptors in the striatum: D1 for the direct pathway and D2 for the indirect. D2 receptors are more significantly implicated in HD. This makes sense, given that the indirect pathway is affected first. Charvin et al. suggest that D2 receptors are over-stimulated. Their theory also says that, as dopamine passes through the D2 receptors, it contributes to the formation of aggregates (or clumps) of the mutant huntingtin protein within the cell. Aggregates of mutant huntingtin are a common pathological marker in HD, meaning that they are present in cells affected by HD. It is unclear, however, what the function of these aggregates actually is. They may be harmful, helpful, or not have any effect on the cell at all. (For more information on protein aggregates, click here).

Scientific studies have consistently noted that dopamine receptors (D1 and D2) are depleted in HD. This may seem strange, as we have been suggesting that the presence of dopamine (or perhaps the excess of dopamine) is the reason why HD motor symptoms occur. Although the depletion of receptors is well known, the cause of the depletion is not. D2 receptors, for the indirect pathway, are depleted first, with more D1 receptors, for the direct pathway, disappearing as HD progresses. One possibility is that too much dopamine may be toxic to the receptors, thus killing them off. It may also be the case that cells try to protect themselves from an excess of dopamine, or its toxic influence in the presence of mutant huntingtin, by actively losing receptors. Another possibility is related to brain-derived neurotrophic factor (BDNF). BDNF is a chemical that protects cells in the brain, and its function has been shown to be impaired in HD. The loss of BDNF could make it much easier for receptors to be damaged, as well as allowing for the mutant huntingtin/dopamine synergistic damage to occur in the first place. (For more information on BDNF, click here). It is also possible that mutant huntingtin harms receptors directly. Regardless of the specific cause of receptor depletion, much damage from dopamine can occur by the time depletion becomes significant. Additionally, if the striatum is absorbing less dopamine, an increased release of dopamine could be triggered in the substantia nigra. A reduced number of receptors can also lead to greater sensitivity of the remaining receptors, ultimately resulting in more dopamine absorption and damage. As you can see, cell-to-cell communication is very complex and intricate. Though this fact makes it difficult to determine just how HD affects the brain, it does give researchers many ideas about what to look at next, as well as offer many possibilities for treatments.

So what does all this mean for HD treatments? Currently in the U.S. there are few medications that are prescribed to treat motor symptoms of HD, and none that are particularly aimed at chorea. However, experimental drugs that deplete dopamine have been reported to have positive effects on motor symptoms. The best-studied drug, tetrabenazine, should soon be available in the U.S. and will be discussed in detail in the chapter linked to below. As we learn more and more about the cause of HD damage in the brain, we can develop new treatments that are aimed at specific mechanisms. Future medications may target ROS production, dopamine absorption through D2 receptors, or initiation of the c-jun pathway, to name a few. These new kinds of treatments will hopefully prove to be more effective than current options, impacting the progression of HD in a meaningful way.

Tetrabenazine^

Click here for an article about Tetrabenazine

For further reading^

  1. Bates, G., Harper, P., & Jones, L. Huntington’s Disease. New York: Oxford University Press, 2002. pp. 28-37, 276-281.
    This book is a thorough review of current knowledge about HD, but is very scientifically-oriented.
  2. Canals, J.M., et al. “Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington’s disease.” 2004.Journal of Neuroscience. 24(35): 7727-7739.
    An article about BDNF and HD.
  3. Charvin, D. “Unraveling a role for dopamine in Huntington’s disease: the dual role of reactive oxygen species and and D2 receptor stimulation.” 2005. PNAS? 102(34): 12218-12223.
    This article presents the possible mechanisms for how dopamine may damage striatal cells.
  4. Dr. Joseph F. Smith Medical Library. “Huntington’s disease.” http://www.chclibrary .org/micromed/00051720.html
    A description of motor symptoms and alternative treatments for HD, such as occupational, speech, and physical therapies.
  5. Emedicine.com. “Huntington disease dementia.” http://www.emedicine.com/me d/topic3111.htm
    Brief review of motor symptoms associated with HD.
  6. Gazzaniga, M.S., Irvy, R.B., & Mangun, G.R. Cognitive Neuroscience: The Biology of the Mind. New York: W.W. Norton & Company, 2002. pp. 488-492.
    This is a textbook covering many topics in neurobiology. It is rather technical.
  7. HDNY at Columbia University. “Speech pathology”: http://www.hdny.org/speech.html, “Social implications of motor disorders”: http://www.hdny.org/problems.htm, “Environmental adjustments”: http://www.hdny.org/rehab.html
    The HDNY website is very helpful as a general resource, even outside the NY area. These pages are particularly relevant to motor symptoms.
  8. Health-cares.net. “What is Huntington’s chorea?”: http://neurol ogy.health-cares.net/huntingtons-chorea.php, “What causes chorea?”: http://neurology.he alth-cares.net/chorea-causes.php
    This website discusses HD and other forms of chorea.
  9. Hickey, M.A., et al. “The role of dopamine in motor systems in the R6/2 transgenic mouse model of Huntington’s disease.” 2002. Journal of Neurochemistry. 81: 46-59.
    A good study of dopamine and HD in a mouse model.
  10. Indiana State University. “Huntington’s disease.” http://web.indstate.ed u/thcme/anderson/RPI.html
    This site has a good schematic diagram of motor pathways, and a more involved discussion of energy metabolism in HD.
  11. International Huntington Association. “Huntington’s disease.” http://www.huntington-assoc .com/huntin.htm
    A summary of the progression of HD, in terms of motor, cognitive, and behavioral symptoms.
  12. Jakel, R.J., & Maragos, W.F. “Neuronal cell death in Huntington’s disease: a potential role for dopamine.” 2000. Trends in Neuroscience, 23: 239-245.
    This is a good article that reviews the potential mechanisms for cell damage as a result of HD.
  13. Nieuwenhuys, R., Voogd, J., & van Huijzen, C. The Human Central Nervous System: a Synopsis and Atlas. New York: Springer-Verlag, 1981. pp. 169-173.
    A highly technical book that details neuroanatomy.
  14. Petersen, A., et al. “Mice transgenic for exon1 of the Huntington’s disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine.” 2001. European Journal of Neuroscience. 14:1425-1435.
    This is a rather complex article that discusses the potential for dopamine toxicity in striatal cells.
  15. Pineda, J.R., et al. “Brain-derived neurotrophic factor modulates dopaminergic deficits in a mouse model of Huntington’s disease.” 2005. Journal of Neurochemistry. 93: 1057-1068.
    More on BDNF.
  16. Reynolds, D., et al. “Dopamine modulates the susceptibility of striatal neurons to 3-nitropropionic acid in the rat model of Huntington’s disease.” 1998. Journal of Neuroscience. 18(23): 10116-10127.
    This article is one of the earlier articles to show that dopamine is important to cell damage in HD.
  17. UCLA Medical Center. “How is Huntington’s disease treated?” http://neurosurgery.ucla.edu/Diagnoses/Movement/MovementDis_2.html
    A brief overview of medical and surgical treatment options, from the neurosurgery department at UCLA.
  18. We Move. “Medical management of Huntington’s disease.” http://www.wemove.org/hd/hd_tr e_mm.html
    A brief discussion of available medical treatments for HD and their potential consequences.

C. Tobin 6-29-06

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The Behavioral Symptoms of Huntington’s Disease

Behavioral-Symptoms-of-HD

Huntington’s Disease (HD), an inherited neurodegenerative disease, damages specific areas of the brain, resulting in movement difficulties as well as cognitive and behavioral changes. Behavioral changes are a characteristic feature of HD and are often the most distressing aspect of the condition for individuals and families dealing with HD. Although there is a great deal of variation in behavioral symptoms among individuals with HD, HD damages specific parts of the brain, resulting in specific and predictable behavioral changes. However, it is important to look at what may be triggering the behaviors in order to provide an environment that minimizes difficult behaviors, behaviors that disrupt the ability of the individual or caretaker to function effectively in a safe environment.

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The Cognitive Symptoms of Huntington's Disease

Cognitive-Symptoms-of-HD

Huntington’s Disease (HD), an inherited neurodegenerative disorder, damages specific areas of the brain, resulting in movement difficulties as well as cognitive and behavioral changes. The term “cognitive” refers to tasks of the brain that involve knowing, thinking, remembering, organizing, and judging. Certain changes in cognitive abilities are characteristic of HD and can significantly impact the lives of individuals with the disease. For example, cognitive changes may affect the ability of a person with HD to work, manage a household or properly care for him or herself

range folding marker basic control

What are some of the cognitive abilities that may be impaired by HD?^

Communication^

Communication is a complex process, requiring the cognitive ability to express and understand as well as physical abilities such as muscle control and breathing. Typically, neural degeneration, resulting from HD, begins in the core of the brain at the caudate nucleus and may spread to areas on the left and right side of the brain, such as the control centers for cognitive function, speech and language. Thus, communication problems tend to become more prominent as the disease progresses.

Throughout the course of the disease, communication problems vary in nature and severity. However, variations in the nature and severity of communication problems also occur from person to person. While one individual may have difficulty initiating conversation, another may have very little difficulty initiating, but severe difficulty word-finding (an aspect of memory recall). Although there are a number of communication problems that may arise for people with HD, the most common communication difficulties are four: speaking clearly, initiating conversation, organizing what is to be said and understanding what is being said.

Fig X-1: Damaged Neurons

As HD damages neurons in the caudate, proper regulation of motor information that tells the body how to move specific muscles at precise times may be impaired. The caudate’s inability to regulate motor information can result in slurred speech and stuttering as well as the uncontrolled bodily movements, often referred to as chorea.

The ability to initiate conversation or activities is a very complex brain function. Damage to the caudate affects the brain’s ability to regulate the sequence and amount of information being transmitted, which may result in difficulty starting and stopping communication. The inability to initiate conversation may also be the result of word- finding difficulty. As neurons in the caudate die, the intact neurons have more difficulty sending information along the neural “circuit.” For example, it may take longer than expected for a person with HD to answer a question because it may be more difficult to find the right word. While word-finding is often impaired, knowledge of vocabulary is retained.

As the caudate and its connections with other areas of the brain deteriorate, some kinds of information may not reach the frontal lobes. Without the frontal lobes to sequence and prioritize outgoing information, the speech of a person with HD may become garbled or seemingly illogical. Damage to the caudate, resulting in impaired access to the frontal lobes may also make it difficult for an HD-affected person to understand what is being said; however, the ability to understand usually remains intact, even in the later stages of the disease. For example, each word of a sentence may be understood, but the frontal lobes and caudate may not be able to organize them properly, possibly resulting in miscommunication. This inability to organize incoming information can also contribute to a slowed response time, even if comprehension remains normal.

If you are interested in reading about strategies and tools that may improve communication for and with a person who has HD, click here.

Memory^

An individual suffering from the cognitive symptoms of HD may have memory difficulties. It is important to note that the memory problems that can occur in people with HD are different from the memory difficulties that can occur in people with Alzheimer’s Disease. Whereas people with Alzheimer’s Disease may get lost in familiar places or forget the names of familiar people, individuals with HD will know and recognize people as well as places.

Tbl X-1: Comparison of Huntington's Disease & Alzheimer Disease

(Table adapted from Paulsen Understanding Behavior in Huntington’s Disease)

Throughout the course of HD, there are two primary memory difficulties that result from cognitive impairment: learning new information and recalling stored information. The impaired ability to learn new information may be the result of damaged neural connections between the frontal lobes and the caudate in the brain. Without efficient use of the frontal lobes, the brain cannot effectively organize and sequence the information to be learned. For example, learning a new phone number may be very difficult for an individual with HD because the brain may not organize or group the numbers together in a way that is easy to remember. For example, the series of numbers “3456978” is much more difficult to remember than “3-4-5-69-78.” When information is not organized in an efficient manner, retaining and recalling the learned information is very difficult.

Fig X-2: Recognition vs. Recall

Recalling stored information is the other primary memory problem for people with HD. For example, a hypothetical person, Silvia, knows what she had for dinner last night, but may not respond very quickly when asked. However, if you ask her whether she had pizza or chicken, she’ll be able to correctly identify which of the two choices she had for dinner. The neurodegenerative nature of HD disrupts the brain’s search mechanism, which makes recalling stored information more difficult, although the memory likely remains intact and can often be recalled through cues or recognition. Also, the person suffering from memory difficulties usually maintains the ability to understand and comprehend information.

Although most memories remain intact, motor memories are often impaired. Motor memories, such as driving a car or tying shoes, are considered implicit or “unconscious” memory. The impairment of these motor memories means that a person has to rely on “conscious memory” to perform these tasks, which requires more concentration. Since these simple, once automatic, tasks may require more concentration, people with HD often have difficulty multi-tasking or dividing their attention. For example, an individual suffering from memory problems due to HD may have difficulty making dinner while listening to the radio.

Tbl X-2: Memory Functions & HD

Recognition memory: stored information can be recalled through a cue. For example, an individual may not remember what time his haircut appointment is scheduled for, but when asked, “are you getting your haircut at 1:00 or 2:00?” he remembers that the appointment is at 2:00

Long-term memory: stores an unlimited amount of rehearsed information; each memory can be stored for a long period of time

Language comprehension: ability to understand the meaning of words as well as how they are organized in order to understand what is being said

Memory retrieval: recalling stored information

Verbal fluency: ability to use and organize words in order to clearly express thoughts, feelings and ideas

Word finding: recalling and using the proper word to communicate

Executive Functions^

Critical to our ability to function effectively at home or work, the “executive functions” include prioritizing, problem solving, judgment, abstract thinking, controlling emotions and awareness of self and others. The frontal lobes, often referred to as the “boss” of the brain, are in charge of the executive functions. The part of the brain responsible for regulation information being sent to the frontal lobes is the caudate nucleus. When HD destroys neurons in the caudate nucleus, a person with HD may have difficulty efficiently performing tasks that were previously simple, such as running errands.

Many of the executive functions that may be impaired in individuals with HD fall into one of three categories: awareness, organization and regulation.

Awareness^

Commonly, denial is used to describe the inability to accept the reality of a distressing circumstance. HD sufferers may deny having HD or be unable to recognize their disabilities. However, this denial is not under the individual’s control, so a lack of awareness or “unawareness” may be a more accurate word for people with HD.

Due to HD, circuits connecting the caudate nucleus, frontal, and parietal lobes may incur damage, resulting in a lack of self-awareness. People with HD may be unable to recognize disabilities or evaluate their own behavior. The inability to evaluate one’s own performance may cause sufferers to be unaware of mistakes that are evident to others. Damage to these neural connections may also impair the ability to experience a range of subtle emotions and see another’s point of view, possibly making social and personal relationships more difficult.

Unawareness often plays a role in seemingly irrational behaviors. For example, a person may become upset if he or she is not allowed to go back to work or live independently, because of the unawareness of failing capabilities. However, a person may be willing to talk about his or her capabilities, but still be unable to acknowledge that failing capabilities are the result of HD. Unawareness, a behavioral as well as a cognitive symptom, is generally accepted as an untreatable component of HD. To learn about the behavioral symptoms of HD, click here.

Organization^

Since HD damages the caudate nucleus, many aspects of behavioral and intellectual functioning can be affected. The task of the caudate is to organize, regulate and prioritize information transmitted from many areas of the brain to the frontal lobes. If the information reaching the frontal lobes is not organized as a result of HD, the individual with HD may experience difficulty organizing his/her thoughts and activities as well.

In order to plan and prioritize efficiently, our brain must be able to organize activities in a logical order, evaluate all of the steps involved in accomplishing a task, and even think about one particular task while performing another. As a result of the damaged caudate, the brain of an individual with HD may not be capable of performing in such a manner. For example, a person without HD may spend one hour on a trip to the grocery store and the bank. However, it may take a person with HD two or three hours to accomplish this same task. While at the grocery store he or she may have to look for each item in the order of the list, possibly failing to get two items from the same aisle because they appeared in different places on the list.

A diminished ability to make decisions may also become a problem as a result of the brain’s failing organizational capabilities. If asked the question, “What would you like to have for dinner?” it may take a while for the brain of a person with HD to organize the words into an understandable question, retrieve the memories of past dinner items, process the feelings regarding each dinner item, and organize the words into a logical response. This difficulty may also be due to memory impairments resulting from HD. Thus, the process of decision making is drastically simplified if a person with HD is given choices, which allows the brain to recognize memories rather than retrieve them. Shorter sentences may also aid in the decision making process, as they contain fewer words for the brain to organize.

Another function affected by the impairment of the brain’s organizational capacity is attention. While simple attention, the ability to focus on one activity, often remains intact, sustained attention as well as divided attention may become impaired. As a result of memory impairments, “unconscious” tasks that were once automatic may require intense concentration. This makes dividing one’s attention very difficult. For example, it may be difficult for a person with HD to walk while carrying on a conversation. With the loss of motor memories, he or she may have to consciously think about each step forward, making conversation difficult. To read more about memory impairment as a cognitive symptom of HD, click here.

Regulation^

The caudate nucleus serves primarily as a regulator and organizer. It controls the order and amount of information traveling from particular areas of the brain to the frontal lobes. As HD progressively destroys the caudate, it may become difficult for individuals with HD to initiate, maintain, and/or stop behaviors or thoughts.

As mentioned above, the ability to initiate activities or conversation is a complex brain function. Damage to the caudate disrupts the brain’s ability to regulate the sequence and amount of information being transmitted, which may result in difficulty starting and stopping communication or activities. The diminished regulatory abilities of the caudate may also result in the inability to maintain an activity or conversation. However, this may be due to the impairment of sustained attention as well. For example, an individual with HD may be able to begin folding laundry but quickly become unable to focus on the task at hand due to distractions. If the radio is playing in the room, the individual may focus his or her attention on the music and be unable to re-initiate and complete the task of folding laundry.

Another possible result of the caudate’s inability to regulate the amount of information traveling to the frontal lobes is a lack of emotional control. A person with HD may over-express a feeling of slight frustration or irritation in the form of a temper tantrum or aggressive behavior. Although the emotion itself is often a legitimate response to something in the individual’s environment, the caudate cannot regulate the proper amount to be expressed. To read about the behavioral symptoms of HD, including frustration, apathy and others, click here.

Visual Spatial Ability^

Visual spatial ability is the ability to perceive one’s body position in the environment. An individual’s perception of his or her body position is useful for judgment of where he or she is in relation to walls or how close his or her hand is to a burner on the stove. Impaired visual spatial ability is often evident even in the early stages of HD. Most commonly, the individual suffering from cognitive symptoms of HD is aware of his or her visual spatial impairment.

For example, due to a diminished visual spatial ability, it may be more difficult for a person with HD to read a map or follow directions, since most directions are given using spatial cues, such as “east” and “west” or distances measured in miles. However, a person suffering from this cognitive symptom of HD may be able to follow directions if they are given using geographic markers, such as: “Go straight on Campus Drive until you reach a stoplight. Turn left and go past the Pet Store. The Post Office will be on the left side of the street with a flag pole in front.” For an individual suffering from visual spatial impairment, directions using “left” and “right” or geographic markers are easier to follow because they do not require the individual to orient his or her body in a particular direction. Regardless of which direction a person is facing, “left” is one way and “right” is the other. However, depending on the orientation of one’s body, “east” may be behind, to the right, to the left or in front of him.

Reading difficulties may also be the result of visual spatial impairment; however, the inability to maintain attention may be a contributing factor as well. For information about attention impairments as a cognitive symptom of HD, click here.

What causes the cognitive symptoms?^

As a neurodegenerative disease, HD damages many neurons and neural connections within the brain, potentially causing cognitive impairment. Most of the damage occurs in the caudate nucleus and putamen, which are structures of the basal ganglia. To learn more about these brain structures, click here. The primary function of the caudate is the regulation and organization of information being transmitted to the frontal lobes from other areas of the brain. The frontal lobes are responsible for many important tasks, some of which are:

  • Organizing
  • Prioritizing
  • Controlling impulses
  • Self-awareness
  • Initiating and ending activities

Thus, damage to the many connections between the caudate and frontal lobes can significantly impair cognitive abilities, such as reasoning, planning, attention, memory, and learning. To read about neurons and neural connections, click here.

The neurodegenerative changes that occur within the brain of a person who has HD are generally the primary cause of the cognitive symptoms of HD, as well as behavioral changes and movement difficulties. An individual suffering from the cognitive symptoms of HD may have difficulty effectively prioritizing his or her daily activities, initiating conversation or activities, recalling memories or making decisions. However, it is important to remember that the cognitive as well as behavioral and physical symptoms of HD vary from person to person. To learn about the behavioral symptoms of HD, click here.

How do the cognitive symptoms change as HD progresses?^

As a general rule cognitive impairments tend to increase in severity as HD runs its course. However, only a few longitudinal studies have been done on the cognitive symptoms of HD, and thus, research has not determined whether the severity of a cognitive symptom can be used as a marker for the underlying progression of the disease.

Although the symptoms of HD vary significantly from person to person, there are some general trends among individuals. Speed of mental processing, organization, and initiation are commonly impaired early in HD and may worsen during the intermediate stages. While individuals with HD are often unable to speak or express their views in the later stages of HD, some cognitive abilities, such as the ability to understand incoming information, may remain relatively intact.

Fig X-3: Common Progression of Cognitive Stages in HD

Do the cognitive symptoms of HD vary from person to person?^

The expression of HD varies significantly from person to person. Although HD is a progressive disease for affected individuals, there is considerable variation in the type and severity of symptoms a person with HD may experience. Some individuals may experience a number of cognitive and behavioral symptoms and fewer physical symptoms, whereas others may suffer more from physical symptoms, such as chorea. The variation in severity means that while some of the cognitive symptoms may be quite pronounced for one person, those particular symptoms may be much less evident in another.

Due to the variation in the type and severity of cognitive symptoms, it may not be useful to use them as an indicator for the onset of HD in an at-risk individual or to diagnose the individual with the disease. Many of the early cognitive symptoms of HD, such as forgetfulness, lack of initiation or fumbling are also fairly common among individuals who are not at risk for HD. “Symptom watching” by individuals at risk for HD may result in a misinterpretation of these thoughts, actions or behaviors as HD. Genetic counselors may be contacted if symptom-watching or anxiety due to being at-risk for HD begins to interfere with one’s ability to function effectively.

Are there treatments available for the cognitive symptoms of HD?^

At the time of this writing (April 2003), there is no cure for the cognitive symptoms of HD or the disease itself. The cognitive symptoms of HD are due to the damage of neurons and neural connections in the brain, which at this time are considered irreversible. However, scientists and researchers continue to investigate the brain’s ability to produce new neurons as well as its ability to form new connections between neurons. For more information about the brain’s natural reparatory ability, click here.

Fortunately, there are a number of strategies for coping with and enhancing cognitive abilities impaired by HD. For example, maintaining a calm, predictable environment and establishing routines can improve organization and planning as well as minimize the occurrence of emotional outbursts. A predictable, routine environment enables a person suffering from the cognitive symptoms of HD to organize daily tasks and adhere to that schedule, resulting in fewer organizational or planning problems. There are a number of resources that provide strategies for improving the cognitive symptoms of HD. If you are interested in learning more about these strategies, click here.

Although there are strategies and treatments that can improve the physical, behavioral and cognitive symptoms of HD, there are currently no treatments available that slow down the progression of HD. However, research continues with the growing hope of discovering effective treatments as well as a cure for HD. For more information on potential treatments for HD, click here.

For further reading^

  1. American Speech-Language-Hearing Association. Huntington’s Disease. http://www.asha.org/speech/disabilities/Huntington-Disease.cfm
    Much like a brochure, this resource explains many of the communication and swallowing problems that may occur as a result of HD. It also lists ways in which a speech-language pathologist can help minimize difficulties.
  2. Australian Huntington’s Disease Association. Information – Huntington’s Disease http://www.ahda.asn.au/content/pages/page.asp?iPage=5
    This website provides basic information about HD as well as support for individuals with HD and their families.
  3. Huntington’s Disease Association. Fact Sheet 10. Behavioral Problems in Huntington’s Disease. http://www.hda.org.uk/charity/download.html
    This clearly-written Fact Sheet is just one of the many informative and helpful Fact Sheets available at this site.
  4. Paulsen, Jane S. “Understanding Behavioral Changes in HD: The Neuropsychology of HD and Strategies for Intervention.” International Huntington Association, 2002. http://www.huntington-assoc.com/jane.html
  5. Paulsen, J. “Understanding Behavior in Huntington’s Disease” (2nd ed.). Huntington’s Disease Society of America, Inc, 1999.
    This is an easy to read and extremely informative resource with the purpose of providing practical and helpful information about the behavioral as well as cognitive symptoms of HD.
  6. Rosenblatt, A., Ranen, G., Nance, M. & Paulsen, J. “A Physician’s Guide to the Management of Huntington’s Disease.” (2nd ed.) Huntington’s Disease Society of America, Inc., 1999.
    This is a guide specifically for physicians. It explains the symptoms of Huntington’s Disease and methods for providing optimal management of the symptoms.
  7. South Shore Neurologic Associates (SSNA). HD: Cognitive Disorders. http://www.southshoreneurologic.com/move-dis/hd/hd-cognitivedisdr.html
    The aim of this site is to provide information and support for individuals with neurological disorders. While there is a substantial amount of information on HD, the information itself isn’t well-organized. However, this site is still a valuable resource for those affected by HD.

K.Hammond 3-29-03; recorded by B. Tatum 8/21/12

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