Huntington Disease Dementia

Figure 1: Alzheimer's Disease Education and Referral Center, National Institute on Aging

• Huntington disease (HD) is a devastating disorder that destroys nerve cells (neurons) in parts of the brain. It also lowers levels of chemicals called neurotransmitters that carry signals in the brain. Loss of these cells and neurotransmitters causes uncontrolled movements, loss of mental abilities, and changes in personality, emotional state, or behavior.
• Mental, emotional, or behavioral decline severe enough to interfere with the ability to carry out everyday activities is known as dementia.
• Huntington disease has been known for hundreds of years. In 1872, Dr. George Huntington became the first to publish a detailed description of the disease that has become linked with his name. Even at that time, scientists realized that the disease is hereditary (passed down in families).
• Huntington disease is one of the most common genetic disorders. The disease affects all races and ethnic groups but is most common among white people of European descent.
• The disease usually affects people in their 30s and 40s, although it can start at almost any age.
• Huntington disease was first described as a movement disorder. It used to be called Huntington chorea.
• Chorea is a type of abnormal movement. The word “chorea” comes from the same root as “choreography.” It refers to the writhing, twisting, dance-like movements typical of the disease.
• While the movement disorder of HD causes significant disability, the mental and behavioral changes are actually much more debilitating. These changes worsen over time into severe dementia.

Huntington disease is a hereditary disease. This means it is passed down in families from one generation to the next via an abnormal gene.

Genes are made up of DNA (deoxyribonucleic acid). DNA molecules are made up of building blocks called bases. The 4 bases are adenine, thymine, cytosine, and guanine, called A, T, C, and G for short.

• A gene consists of a sequence of bases that together determine a characteristic or trait, such as eye color or body type.
• Each gene in the body has its unique location somewhere on one of 23 chromosomes.
• Each person inherits 2 of each chromosome, one from his or her mother and one from the father. Thus, each healthy person has 2 copies of every human gene.

The normal HD gene, which is located on chromosome 4, contains the base sequence CAG. The abnormal repetition of this sequence is known as the HD mutation.

• The number of repeats varies and is key to a person’s risk of developing the disease.
• People who have 38 or more CAG repeats in the HD gene are genetically programmed to develop the disease.
• This is determined when the person is conceived.

Huntington disease is an autosomal dominant disorder. This means that the HD mutation takes precedence over the normal gene.

• Each of us inherits 2 copies of each gene, 1 from each parent. A person who has a parent with Huntington disease has a 50% chance of inheriting the HD mutation.
• Inheriting the HD mutation does not automatically mean that the person will develop the disease.
• The number of CAG repeats determines the person’s risk of developing the disease and, to a certain extent, his or her children's risk.
• Occasionally a person with no family history of HD develops the gene abnormality and thus the disease. Such “sporadic” cases are rare.

The HD gene directs production of a protein called huntington. This protein is found in neurons throughout the brain, but its normal function is unknown.

• The abnormal huntington protein produced by the abnormal gene is believed to interact with other proteins to cause destruction of neurons.
• Most of the damage occurs in the basal ganglia, a part of the brain that controls movement and many other important functions.
• The damage also affects parts of the brain that control cognitive processes such as thinking, memory, and perception.

Abnormal movements or emotional or behavioral changes are usually the earliest symptoms to appear in HD. Cognitive disturbances usually appear later in the course of the disease. Emotional, behavioral, and cognitive symptoms usually appear gradually and worsen over time.

The average life expectancy from onset of symptoms is about 15 years. Early onset of the disease, before age 20 years (juvenile HD), is linked to faster progression of symptoms and shorter life expectancy (approximately 8 years). Individuals who inherit the disease from their father tend to develop symptoms much earlier in life than those who inherit it from their mother.

Emotional and behavioral disturbances occur in some people with HD.

• Change in affect: This is a common early symptom. “Affect” means the outward expression of thoughts, feelings, and moods. For example, a person who is normally cheerful may show little feeling at all.
• Depression: Depression is the most common emotional disturbance in HD. Symptoms include sadness, tearfulness, lethargy, apathy, withdrawal, loss of interest in activities once enjoyed, insomnia or sleeping too much, and weight gain or loss.
• Mania: Mania is a state of extreme excitement, restlessness, or hyperactivity with insomnia, rapid speech, impulsiveness, and/or poor judgment. Increased sexual activity or arousal is sometimes a symptom in people with HD.
• Eccentricity, inappropriateness, loss of social manners
• Excess irritability
• Obsessive-compulsive symptoms: Some people with HD develop obsessions (uncontrolled, irrational thoughts and beliefs) and/or compulsions (odd behaviors that must be carried out to control the thoughts and beliefs). They may become preoccupied with details, rules, or orderliness to such a degree that the larger goal is lost. Lack of flexibility or inability to change is common.
• Psychosis: The psychotic person is unable to think clearly or realistically. Symptoms such as hallucinations, delusions (false beliefs not shared by others), and paranoia (suspicious and feeling of being under outside control) are common. The person’s behavior is strange, bizarre, agitated, aggressive, or even violent.
• Suicide: A small percentage of people with HD commit suicide. The worsening dementia often does not affect insight, and a person may become suicidal when faced with the burdens of his or her disease.

Cognitive symptoms include the following:

• Forgetfulness and disorganization - Common early symptoms
• Loss of attention, poor concentration
• Poor judgment
• Problems with abstract thought, reasoning, or problem solving
• Spatial disorientation
• Difficulties with sequencing, organizing, or planning
• Inability to learn new things
• Inflexibility, problems adapting to change
• Memory loss - Typically occurs later in the disease

Most people with HD retain their insight, factual knowledge, and intelligence quotient (IQ) score relatively well into the disease process. Use of language may or may not be impaired.

Any loss of physical control or change in mood, behavior, or mental abilities warrants a visit to your health care provider.

A combination of movement disorders and mental, emotional, or behavioral changes can be caused by several different conditions. Of course, HD is considered first in a person with a known family history. A person having any such combination of symptoms will probably be referred to a specialist in disorders of the brain and nervous system (neurologist).

The neurologist will ask many questions about the symptoms and how they started, other medical problems now and in the past, family medical history, medications, work and travel history, and habits and lifestyle. A detailed physical examination will include tests of movement and sensation, coordination, balance, reflexes and other nervous system functions, and mental status. The main goals of the medical interview and examination are to inventory the exact disabilities and to rule out other conditions that can cause similar symptoms.

Lab tests

These tests are used to confirm the diagnosis of HD and dementia.

• DNA repeat expansion: The test identifies the HD mutation. It uses a technique called PCR to measure the number of CAG repeats in the HD gene. This test is very accurate in confirming the disease, because no other similar disease has the gene mutation.
• Homovanillic acid: Homovanillic acid is a product of the neurotransmitter dopamine, which plays an important role in movement. The amount of homovanillic acid in the cerebrospinal fluid is lower in people with HD than in healthy people. Cerebrospinal fluid is a clear fluid that surrounds and helps protect the brain and spinal cord. The degree of reduction in homovanillic acid level is a marker of the severity of dementia and life expectancy in HD. A sample of the fluid is obtained for this test by lumbar puncture (spinal tap). This procedure involves using a hollow needle to pierce the space around the spinal cord in the lower back.

Imaging studies

Brain scans can be useful in measuring the extent of brain damage in the disease.

• CT scan or magnetic resonance imaging (MRI) of the brain shows atrophy (shrinkage) of the parts of the brain affected by HD.
• Single-photon emission computed tomography (SPECT) scan shows changes in metabolism and blood flow in the parts of the brain affected by HD.
• Position-emission tomography (PET) scan shows changes in brain function that often occur before symptoms begin in HD. This scan is available only in a few large medical centers. Its usefulness in HD is still being studied.

Neuropsychological testing

No medical test definitively confirms cognitive decline or dementia in HD. The most accurate way to measure cognitive decline is through neuropsychological testing.

• The testing involves answering questions and performing tasks that have been carefully designed for this purpose. It is carried out by a specially trained psychologist.
• Neuropsychological testing addresses the individual’s appearance, mood, anxiety level, and experience of delusions or hallucinations.
• It assesses cognitive abilities such as memory, attention, orientation to time and place, use of language, and abilities to carry out various tasks and follow instructions.
• Reasoning, abstract thinking, and problem solving are tested.
• Neuropsychological testing gives a more accurate diagnosis of the problems and thus can help in treatment planning.
• The first test results are used as a baseline for measuring changes in cognitive abilities. The tests may be repeated periodically to see how well treatment is working and to check for new problems.

HD is a devastating condition that affects every aspect of life. No available treatment can halt the progression of dementia in HD. Maximizing the affected person’s quality of life while minimizing the burden on family caregivers is the overall goal of treatment. Treatment is focused on relieving symptoms and improving function.

The day-to-day care of a person with HD falls largely to family caregivers. Medical care should be provided by a professional team. The team might include a psychiatrist, an internist or family doctor, a physical therapist, a dietitian, a social worker, and other providers. In most cases, the person’s care is overseen by a neurologist.

Research is being conducted to find ways to reverse the HD mutation or to stop the degeneration of the brain in HD.

With the combination of physical, mental, and emotional disabilities that come with advancing HD, the affected person soon becomes unable to care for himself or herself. In many cases, the person remains at home and family caregivers provide most of the care. Caregivers are responsible for balancing the needs of the person with those of the family and caregivers.

Safety is an important issue for the affected person and for the caregivers.

• The person with HD requires supervision. He or she may get into dangerous situations in the home, wander off, or even attempt to harm himself or herself.
• As much as possible, hazards should be removed from the home to prevent falls and other injuries.
• The person with HD may become agitated or even violent. In this condition, he or she could harm a caregiver or himself or herself.
• As symptoms worsen, the person with HD should stop driving a car or using dangerous equipment.

Individuals with HD should remain physically, mentally, and socially active as long as they are able.

• Daily physical exercise helps the body and mind function and maintains a healthy weight. Many people are able to continue walking for some time as the disease worsens. Some require special shoes, braces, or other equipment to help them walk. A physical therapist can recommend exercises appropriate for the person’s physical abilities.
• The individual should engage in as much mental activity as he or she can handle. Puzzles, games, reading, and safe hobbies and crafts are good choices. These activities should of course be matched to the person’s physical abilities. They should be of an appropriate level of difficulty to ensure that the person does not become overly frustrated.
• Social interaction is stimulating and enjoyable for most people. The person should be included in family meals and activities to the greatest extent possible. A local community center may have scheduled activities that are suitable.

Loss of coordination and swallowing problems may make eating and drinking difficult for people with HD. It is very important that the person with HD consume enough calories and nutrients.

• Caregivers should adapt foods to make them easier to eat. This may mean changing the consistency or the size of bites.
• A dietitian can give advice to ensure that nutritional needs are met and to help the person eat independently for as long as possible.
• Swallowing therapy is available. It usually works best if started before swallowing problems become severe.

As the person's dependency increases, caregivers may begin to feel more burdened.

• Families should plan for the possibility of having additional support at home or for possible transfer to a long-term care facility.
• Many families choose to use some form of respite care (eg, home health aid, daycare, brief nursing home stay).
• Your social worker may be helpful in arranging this.

No known treatment improves cognitive deficits in HD. Emotional and behavioral disorders, especially depression, mania, and psychosis, may improve with medication. Medication controls symptoms, but it does not cure the underlying disease.

Depression is very common in people with HD. Medication can relieve depression symptoms and improve the person’s quality of life.

Psychosis is probably the most disruptive mental problem in HD. Psychotic symptoms are distressing to the affected person and to loved ones. Treatment can help increase the comfort and safety of the affected person, family members, and caregivers. Medication is definitely indicated if the person’s agitation, combativeness, or violent behavior becomes a danger to self or others.

Drugs are used to control emotional and behavioral symptoms in persons with HD.

Antidepressants

These drugs help relieve symptoms such as sadness, withdrawal, apathy, sleep problems, and suicidal thoughts.

• There is a wide range of antidepressant drugs. The choice of antidepressant is usually based on side effects. The goal is to choose the drug that has the fewest side effects for a specific person.
• Antidepressant drugs may relieve psychotic symptoms, such as agitation and aggression, if they are fairly mild.
• In some cases, successful treatment of depression can at least partly relieve cognitive problems.
• The best choices of antidepressants for many people with HD are the selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft).
• Drugs from another class of antidepressants called the tricyclics are sometimes used. Examples include nortriptyline (Pamelor) and desipramine (Norpramin).

Antipsychotics

These drugs help relieve symptoms such as agitation, screaming, combativeness, or violence. They also relieve symptoms such as paranoia, delusions, and hallucinations.

• There is a wide choice of antipsychotic drugs. The drug is usually chosen on the basis of side effects and what will be easiest for the person to tolerate.
• In some people, these drugs can worsen muscle rigidity and stiffness, which worsen the movement problems in HD.
• They also cause excessive sleepiness in some people.
• These drugs are given at the lowest doses possible to avoid these side effects.
• Examples include haloperidol (Haldol), thioridazine (Mellaril), risperidone (Risperdal), and clozapine (Clozaril).

Benzodiazepines

These drugs are most often used to rapidly calm a person who is extremely agitated and/or anxious. These drugs are not widely used in people with dementia because they can actually increase memory problems and confusion. An example is lorazepam (Ativan).

Anticonvulsants

These drugs are used mainly to stop seizures. They tend to stabilize mood and are sometimes used in people who are not psychotic but are agitated or having mood swings. They can also be used for persons with psychotic symptoms that do not get better with antipsychotic treatment. An example is carbamazepine (Tegretol).

After HD has been diagnosed and treatment begun, the individual requires regular checkups with the neurologist and other members of the care team.

• These checkups allow the neurologist to see how well treatment is working and to make adjustments as necessary.
• They allow detection of new medical and behavior problems that could benefit from treatment.
• These visits also give the family caregiver(s) an opportunity to discuss problems with the individual’s care.

The person with HD eventually becomes unable to make decisions about his or her care. It is best for the person to discuss future care arrangements with family members as early as possible, so that his or her wishes can be clarified and documented for the future. Your social worker can advise you about legal arrangements that should be made to ensure that these wishes are observed.

Right now, there is no way to prevent HD. It is genetically programmed before birth.

Much research in HD is focused on correcting the problem before brain damage can occur.

HD starts slowly but finally results in severe brain damage. People with the disease gradually lose cognitive functions, ability to carry out everyday activities, and ability to respond appropriately to their surroundings. They eventually become completely dependent on others for care. These losses cannot be stopped, but the speed with which they occur varies by person.

HD is considered to be a terminal disease. The actual cause of death usually is a physical illness such as pneumonia, heart failure, or respiratory failure. Such illnesses can be debilitating in a person who is already weakened by the effects of the disease. Injuries, choking, and suicide are other causes of death. On average, a person with HD lives about 15 years after the disease is diagnosed. Persons with the juvenile form of the disease rarely live to adulthood.

The disease affects every member of the family. Knowledge of the outcome creates a substantial emotional and psychological burden for affected persons and their family members.

A genetic test is available that predicts a person’s risk of developing HD. Because of the many issues that arise from a test that predicts the possibility of developing such a devastating disease, genetic counseling should always be provided before testing. A genetic counselor can acquaint an individual and family members with all the implications of testing.

The diagnosis of HD is devastating for the affected person and family members.

• Learning you have HD is particularly difficult because you probably have watched family members stricken with the disease and know what will happen.
• You probably fear the mental and physical declines that come with the disease.
• You may worry about your family and how they will cope with your illness and death.
• Depression, anxiety, withdrawal, resentment, despair, and rage are common reactions.

Talking about your feelings and concerns may help.

• Your friends and family members can be very supportive. They may be hesitant to offer support until they see how you are coping. Don't wait for them to bring it up. If you want to talk about your disease, let them know.
• Some people don't want to "burden" their loved ones, or they prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if you want to discuss your feelings and concerns. Professionals on your care team may be able to help, or they should be able to recommend someone who can.

If you are a caregiver for a person with HD, you know what a difficult job this is.

• It affects every aspect of your life, including family relationships, work, financial status, social life, and physical and mental health.
• You may feel unable to cope with the demands of caring for a dependent, difficult relative.
• Besides the sadness of seeing the effects of your loved one’s disease, you may feel frustrated, overwhelmed, resentful, and angry. These feelings may in turn leave you feeling guilty, ashamed, and anxious. Depression is not uncommon.

Different caregivers have different thresholds for tolerating these challenges.

• For many caregivers, just “venting” or talking about the frustrations of caregiving can be enormously helpful.
• Others need more, but may feel uneasy about asking for the help they need.
• One thing is certain, though: If the caregiver is given no relief, he or she can burn out, develop his or her own mental and physical problems, and become unable to continue as a caregiver.

This is why support groups were invented. Support groups are groups of people who have lived through the same difficult experiences and want to help themselves and others by sharing coping strategies. Mental health professionals strongly recommend that family caregivers take part in support groups. Support groups serve a number of different purposes for a person living with the extreme stress of being a caregiver for a person with HD.

• The group allows the person to express his or her true feelings in an accepting, nonjudgmental atmosphere.
• The group’s shared experiences allow the caregiver to feel less alone and isolated.
• The group can offer fresh ideas for coping with specific problems.
• The group can introduce the caregiver to resources that may be able to provide some relief.
• The group can give the caregiver the strength he or she needs to ask for help.

Support groups meet in person, on the telephone, or on the Internet. To find a support group that works for you, contact the organizations listed below. You can also ask your health care provider or behavior therapist or go on the Internet. If you do not have access to the Internet, go to the public library.

For more information about support groups, contact the following agencies:

• Huntington’s Disease Advocacy Center
• National Alliance for Caregiving