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Lifestyle and HD: Table of Contents

Read more about lifestyle and HD!

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Google Glass and HD

The part of the brain most affected by Huntington’s disease, the basal ganglia, are groups of nerve cells (neurons) at the base of the brain. Basal ganglia are responsible for the motor movements of the muscles in the body. When cells in basal ganglia die, a common pathological symptom of HD, a person experiences uncontrollable muscular movements similar to that of fidgetiness. Another disease that produces similar uncontrollable movements symptom is the Parkinson’s disease due to the disease’s effects on a specific area of the basal ganglia called the substantia nigra.

A new app for intelligent glasses, such as Google Glass, might make it possible to improve the gait of patients suffering from Parkinson’s disease.

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Companion Animals and Health

When most people consider therapies, they often think of prescriptions and side effects. However, animal companion therapy is proving to be an effective means of improving well-being among patients. Many of the benefits of animal companion therapy can extend to patients and family members living with Huntington’s disease. This article highlights the physical effects caused by companion animals, as well as opportunities for taking advantage of this type of therapy.

The Physical Effect of Companion Animals^

Stress can have harmful effects on the body’s ability to cope with various health issues. Research consistently shows that exercise and meditation can help manage stress levels. More recently, the scientific community has begun to collect growing evidence that animal companions might have the same effect on the health of patients.

The presence of an animal alone can affect our emotions. Animals are often able to focus people’s attention in a way that is calming or de-arousing (Cirulli et al., p. 342). Since animals, especially dogs, respond with affection and generally pro-social behaviors, they can potentially serve as an “emotional bridge” within therapeutic contexts.

The physical health effects of a companion pet can range from everyday benefits to life-saving changes. Within the first few months of acquiring a pet, patients tend to have lowered risk for cardiovascular disease, increased chances of surviving myocardial infarctions, decreased need of physician services during stressful life events and a reduction in everyday minor health problems.

Many HD patients cite lack of familial support as a major problem. Companion animals could help mediate this gap as icebreakers, bridging people with the outside world and jumpstarting communication and social exchanges that can promote feelings of social integration. Research in nonhuman mammals suggests that oxytocin, a signaling molecule in the brain, helps to increase one’s feeling of reward during social interactions while also increasing bonding between individuals. Oxytocin also assists in responding to social stress for humans. In fact, interacting with a dog caused a significant increase in levels of oxytocin within the human, improving his or her ability to forge new social bonds.

Creating an animal companion relationship^

In the study, Animal-assisted Interventions as Innovative Tools for Mental Health, researchers state that dogs are the ideal animal companions. Over thousands of years of domestication, dogs have been “selected for characteristics that enhance their sensitivity to a wide range of human communicative signals, both visual and acoustic” (Cirulli, p. 341). Dogs develop complex communication systems with humans and are highly interactive. Additionally, dogs provide opportunities for physical, recreational, and social activities. They are easily trained to constructively work in different settings, which explain their use as Seeing Eye and rescue dogs.

HD patients who live in nursing homes are often under great duress, as institutionalization can result in a decreased quality of life and stress due to separation from loved ones. Dog-mediated interventions could improve communication and reduce loneliness and depression.

Furthermore, animal companions could also help children of families experiencing traumatic life occurrences. Animal companions have been shown to influence social, emotional, and cognitive development in children. Parents often report that an animal helps teach children about life events. Children who grow up with pets have an enhanced sense of empathy and responsibility, social status within the peer group, and higher self-esteem and self-confidence.

While the positive aspects of animal companionship seem numerous, there are studies that raise questions about the extent of this impact. Visiting dog programs do not consistently “improve mood, cognitive abilities or social interactions” (Cirulli, p. 344). This might indicate that perhaps longer-term, matched interaction is needed between animal and human to see any effects. In fact, saliva spits revealed that there is a time-dependent increase in behavioral results such as improvement in mood or social bonding, as measured by mood changes and cortisol levels. (Cortisol is a hormone often associated with stress. Long term interaction with animals has shown to decrease levels of this hormone, improving well-being.)

Adding Pets to the Home^

In summary, adopting a companion animal into a Huntington’s disease family or an institution housing HD patients might have marked effects on the well being of various participants. However, there are certain aspects to take into account when making the decision to add a family member to the home. To find more information about the logistics of adopting a pet, visit http://www.aspca.org/adopt/adoption-tips.

If you are concerned with integrating a pet into family experiencing health difficulties, please contact Pet Partners, an organization dedicated to “improving lives through positive human-animal interaction.” Visit their website at http://www.petpartners.org/.

For Further Reading:^

1. Cirulli, Francesca, Marta Borgi, Alessandra Berry, Nadia Francia, and Enrico Alleva. “Animal-assisted Interventions as Innovative Tools for Mental Health.” N.p., n.d. Web. 14 Oct. 2013.
2. Bekoff, Marc, Ph.D. “Pets Are Good for Us: Where Science and Common Sense Meet.”Psychology Today. N.p., 23 July 2010. Web. 14 Oct. 2013
3. Allen, Karen M., Jim Blascovich, Joe Tomaka, and Robert M. Kelsey. “Presence of Human Friends and Pet Dogs as Moderators of Autonomic Responses to Stress in Women.” Journal of Personality and Social Psychology 61.4 (1991): 582-89. Print.
4. Health Benefits of Animals. Pet Partners, n.d. Web. 14 Oct. 2013. .

K. Powers
10/31/2013

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Advocacy: How to Get Involved

This article describes current advocacy efforts, including the Huntington’s Disease Parity Act, Compassionate Allowance List, and how these two types of documents affect the average Huntington’s disease family.

Advocacy, by definition, is the means through which an individual or group attempts to influence public policy. The Huntington’s Disease Society of America website states that advocacy, pertaining to Huntington’s disease (HD), is sharing your personal HD story, as well as asking elected officials to support efforts to “improve access to treatment, medical care and to find a cure.”

Huntington’s Disease Parity Act^

The Huntington’s Disease Parity Act would require the Social Security Administration to revise the disability criteria for those with HD, especially in terms of the language used to approve applicants for benefits. It would also waive the 24-month waiting period for Medicare eligibility for individuals disabled by HD. (To view the actual text of the bill, click here.)

Many individuals experiencing symptoms due to HD are unemployed due to their disabilities. Because of this, they often rely on Social Security Disability Insurance (SSDI). SSDI is based upon the amount of income an individual was receiving when he/she became disabled. Payments often range from $500 to $2,000 a month. However, after qualifying for this insurance, the individuals must wait at least two years before receiving any benefits from the Medicare program. This policy is extremely problematic as many HD patients are under the age baseline for Medicare (65 years old), and yet deteriorate very quickly if symptoms aren’t addressed with proper medical care immediately after diagnosis.

The HD Parity Act would correct this problem by waiving the 24-month waiting period as it did for patients with amyotrophic lateral sclerosis (ALS) in 2000.  (This bill passed as an attachment to an appropriations bill after confirming an influential number of co-sponsors in the House and Senate.) In addition, the SSDI guidelines for HD are extremely outdated, affecting who is approved for the insurance. These guidelines do not recognize the psychological effects of HD, which can appear 10 to 15 years before motor symptoms begin.

Efforts are being made to promote the bill and ensure that it is approved. The bill was first introduced in the House of Representatives by Bob Filner (CA-D) and in the Senate by Senator Kirsten Gillibrand (NY-D) in 2011. Since then the Huntington’s Disease Society of America has been encouraging its support by senators and representatives and has set a goal of obtaining 175 co-sponsors.  However, this goal is flexible as it is ideal to have a majority of Congress support this initiative. Currently, there are 144 co-sponsors. The more senators and representatives in support of this bill, the more likely it will be passed when voted upon.

To check whether or not your elected officials have supported this act, click here.

Compassionate Allowance List Update^

SSA Announces Official Inclusion of Adult-Onset HD to Compassionate Allowance List

On Thursday, December 6, 2012, the Social Security Administration (SSA) announced that adult-onset HD would be added to the Compassionate Allowance List (CAL), along with Juvenile-Onset HD, which was added in April 2012.

The CAL allows those affected by diseases on the roster to enter a fast track for applying to Social Security benefits. This means families affected by HD will no longer face rejection and postponed benefits due to outdated definitions of HD symptoms.  According to the Huntington’s Disease Society of America, the addition to the CAL “also recognizes the cognitive and psychological symptoms of HD and establishes criteria for their use in the qualification process.”

While inclusion on the CAL is a great step forward, there is still a need for the SSA to update their outdated description of HD, which defines the disease as a movement disorder (especially since the CAL language refers back to the SSA definition). CAL will not address issues of insurance. It also does not affect the language used by the SSA which does not include the cognitive and psychiatric aspects of HD, arguably the more debilitating aspects of the disease and the first to appear. These issues, along with the 2-year waiting period for Medicare eligibility, are addressed in the proposed Huntington’s Disease Parity Act, which is currently in need of more co-sponsors in both the House and Senate.

If you are interested in advocating for the HD Parity Act, visit http://www.hdsa.org/living-with-huntingtons/advocacy/ to write your senators and representatives, urging them to co-sponsor this important bill.

In addition, if you or someone you know affected by HD is denied disability, please contact Jane Kogan of the Huntington’s Disease Society of America. You can e-mail her at jkogan@hdsa.org for support and advice on re-applying.

The Fast Facts: A Summary^

The Parity Act Fact Sheet is a quick guide to the basic facts concerning the Huntington’s Disease Parity Act. All of these facts were compiled by the Huntington’s Disease Society of America.

1. Huntington’s disease is the only disease that is neurological, genetic, fatal disease, and rare, yet strikes during one’s working years. It is also the only disease to potentially have total cognitive, motor, and behavioral impairment, all at the same time.

2. The Compassionate Allowance Act eases the wait time for disability insurance review. However, only the Huntington’s Disease Parity Act will update the language, allowing more people with the disease to qualify for disability benefits. That means less people will be denied disability coverage.

3. The Social Security Administration (SSA) has the power to change their definition of HD. Their neurological disability guidelines expired on July 1, 2012. SSA extended their own deadline to publish the new guidelines for an additional two years. Legislation would mandate they speed up the process.

4. The HD Parity Act has an expected $260 million cost over 10 years (starting after the removal of the two-year waiting period). These estimates are based upon the costs incurred by a similar act passed for ALS (amyotrophic lateral sclerosis) in 2000. The cost of removing the two-year waiting period for all diseases is estimated to be around $113 billion over 10 years (2008 Congressional Budget Office).

5. If this legislation were passed, Medicaid savings could potentially lower the total cost of this policy by as much as 20 percent, for a total annual cost of $21 million annually (Strategic Health Care). (Strategic Health Care, a lobbyist group for the HDSA, obtained these numbers from the independent research conducted by Mathematica Policy Research and the Congressional Budget Office.)

6. The support of 218 representatives from the House and 60 senators from the Senate is needed in order to pass a bill. (The Senate number would mean there would be no possibility for a filibuster (an attempt to block  a vote for legislation through methods such as speaking for extended periods of time). In addition, there do not need to be 60 official co-sponsors, but rather 60 Senators who have shown some level of support for the bill.)

7. Members of Congress do not need to sit on the committee of jurisdiction to co-sponsor legislation. Any member of Congress has the power to cosponsor a bill, no matter what committee they serve on.

8. Amyotrophic Lateral Sclerosis (ALS) and End Stage Renal Disease (ESRD) have both received waivers for the two-year Medicare waiting period through Congressional legislation.

Anyone can be an advocate for measures that would improve the lives of those affected by Huntington’s disease. Whether it be sending your representative an e-mail urging them to co-sponsor legislation or fighting discrimination in the workplace, everyone can make a difference.

 

Further Reading^

1. “Bill Text 112th Congress (2011-2012)S.648.IS.” Bill Text of the Huntington’s Disease Parity Act. Kirsten Gillibrand, n.d. Web. 11 Dec. 2012.

 

This is the text of the bill introduced to Congress. View it in its entirety by clicking here.

 

2. “Advocacy.” Www.hdsa.org. N.p., n.d. Web. 11 Dec. 2012.

 

This is the Huntington’s Disease Society of America’s official Advocacy website.

3. “SSA Announces Official Inclusion of Adult-Onset HD to Compassionate Allowance List.” Message to Kristen A. Powers. 7 Dec. 2012. E-mail.

 

This is an e-mail sent out by the Huntington’s Disease Society of America. To view the web version, click here.

KP 02/15/2013

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Medical Marijuana Policy in the United States

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Disclaimer: This article is meant to be purely educational—HOPES neither condones nor condemns the use of marijuana for medicinal purposes.


Throughout the past several decades the use of marijuana for medicinal purposes has received increasingly more attention.  The active ingredient in marijuana belongs to a class of compounds called cannabinoids, which have been used to treat numerous conditions ranging from insomnia and PMS to chemotherapy-induced nausea and appetite loss associated with AIDS therapy.  More recently, cannabinoids have been shown to be effective against motor disturbances in patients with multiple sclerosis.  This latter finding points to a potential use of medicinal marijuana to treat movement problems in Huntington’s Disease.

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Weight Loss: Demystifying a Medical Mystery

While Huntington’s disease is traditionally thought of as a disease of the brain, its effects are much more widespread: many people with HD lose a dangerous amount of weight, complicating a disease that is already complicated enough. Although weight loss is one of the most serious non-neurological problems of HD, scientists don’t fully understand why it occurs. This medical mystery has driven scientists deep into the biology underlying weight loss in HD. Researchers have recently turned up a few potential explanations, and our increased understanding of this symptom is leading scientists to look at possible new ways of treating the disease.

Weight Loss in HD^

People with HD tend to weigh less than those without the disease. A group of researchers from the Huntington Study Group followed 927 people with early-stage HD. For a description of the stages of HD, please click here. The investigators found that people with early-stage HD weighed an average of 10 kilograms (22 pounds) less than age-matched controls, which are people of the same age who don’t have the disease. Another study found that people with HD lose an average of 0.9 pounds per year, which stands in stark contrast to the average American, who gains 0.4-2 pounds yearly.

Unfortunately, while 0.9 pounds doesn’t seem like much, that’s just an average; some people with HD lose so much weight that their health is impacted. Weight loss worsens other aspects of the disease as underweight patients become malnourished and weak. Underweight patients are more susceptible to infection, and take longer to recover from illness, operations, and wounds. Weight loss also increases the likelihood of developing pressure ulcers, commonly known as bedsores, as bedridden patients have less fat tissue to cushion them from pressure. Patients who lose the most weight report a lower quality of life, and are more likely to feel apathetic and depressed. In the late stages of the disease, some patients lose so much weight that they need a feeding tube to stay healthy, as described here. On the other hand, people who start out heavier fare better; people who have a high body-mass index (BMI) when symptoms begin progress more slowly through the disease. Visit this website for an explanation of BMI and a for BMI calculator.

A Medical Mystery^

While weight loss is one of the most serious non-neurological problems associated with HD, doctors don’t understand why it happens. Many suggestions have been put forth, but most of them have been disproved, forcing researchers to dig deeper to understand this phenomenon.

Chorea^

Doctors once believed that weight loss was due to chorea, the uncontrolled movements characteristic of HD. Doctors thought that people with HD lost weight because they burned extra energy as a result of the involuntary movements of chorea. However, three experiments indicate that chorea can’t be fully responsible for weight loss.

The first piece of evidence comes from looking at the early stages of the disease. People who have just been diagnosed with HD – and therefore have very mild symptoms – already weigh less than people without the disease. As mentioned earlier, people in early-stage HD weigh an average of 10 kg less than those who are not affected by the disease. Another group of researchers arrived at similar results; a study of 361 people with early-stage HD found that they have BMIs an average of 2 points lower than those without the disease, even if the patients had just been diagnosed with HD within that year and hadn’t yet begun to experience choreic movements. Researchers concluded that chorea alone could not explain why people with HD have lower BMIs, and that other factors are at play.

Other studies suggest that chorea may not have as much of an impact as doctors once thought. Pratley et al. measured how much movement chorea caused, in an attempt to quantify how much weight patients lose due to choreic movement. After measuring the movements of 17 people with mild to moderate HD for a week, they found that chorea caused people with HD to move more than people without the disease when sedentary: people with HD moved 14% more than people without HD while sitting or lying down. However, people with HD do less voluntary activity. Study participants with HD walked around and exercised less than people without the disease. In the end, Pratley et al. were surprised to discover that sedentary over-activity balanced out voluntary under-activity: people in the early and middle stages of HD don’t actually move more than people without the disease.

A similar study by the European Huntington’s Disease Initiative Study Group (EHDI) measured weight loss in 517 people with HD, and found no correlation between the amount of weight people lost and the severity of their motor symptoms; people with good scores on tests measuring motor symptoms (such as the UHDRS) were just as likely to lose weight as those with bad motor scores. For more information on diagnostic tests like the UHDRS, click here.

The final strike against the chorea theory comes from observations of people with late-stage HD. Weight loss is most drastic in the final stages of HD, despite the fact that chorea has usually ceased and patients are largely bedridden. So while chorea contributes to weight loss in HD, it cannot stand as the sole explanation.

Reduced Food Intake^

Others suggest that people with HD lose weight because they have trouble eating; as the disease progresses, it becomes increasingly difficult to perform the complicated series of movements needed to eat, chew, and swallow.

However, this theory is also not enough to fully explain the weight loss. Studies have shown that people with HD actually tend to eat more than people without the disease; a study of 25 people with HD found that they ate an average of almost 400 calories more each day than people without the disease. Others report that they’ve had patients who eat up to 5000 calories a day – over twice the average daily caloric intake – just to maintain their weight.

So two popular explanations for weight loss in HD – chorea and insufficient diet – cannot entirely explain why people with HD lose so much weight.

Possible Biological Causes^

Though the reasons for the mysterious weight loss are unclear, scientists are currently testing a few ideas.

Abnormalities in Energy Metabolism^

One leading idea has to do with metabolism, the way the body burns calories to produce energy. HD researchers have long suspected that the disease-causing form of huntingtin (hereafter described as mutant huntingtin) interferes with energy metabolism, as described here. Results from a recent study suggest that this interference might contribute to weight loss.

After discovering that weight loss is not correlated with motor symptoms, scientists from the EHDI Study Group looked for other factors that might be to blame. They found that weight loss could be partially predicted by the number of CAG repeats on a patient’s copy of the mutant huntingtin gene; for every additional CAG repeat a patient had, they lost on average an extra 0.136 BMI points (0.8 pounds) over the course of the three year period that the study was conducted. For an explanation of CAG repeats, please click here.

The same holds true in mouse models of HD. The EHDI Study Group found that the more CAG repeats an HD mouse had, the more it tended to eat. Yet paradoxically, the mice with the most CAG repeats lost the most weight. So people and mice with more CAG repeats lose more weight.

The EHDI investigators suspect that this is due to the long tail of the mutant huntingtin protein. People with more CAG repeats produce mutant huntingtin with a longer tail, as described here. The EHDI investigators suggest that the mutant huntingtin protein interferes with the way cells make energy, and that longer-tailed proteins cause more problems. Mutant huntingtin has been shown to disrupt proteins that are needed to make energy and can damage mitochondria, the “energy factory” of our cells, as described here. In support of the theory that proteins with longer tails are more problematic, scientists at the MacDonald lab in Boston studied cells engineered to express mutant huntingtin. They found that cells with more CAG repeats made less ATP, the energy currency of the cell. So it seems possible that the more CAG repeats individuals have, the less efficient their cells are at converting calories to energy.

Hormonal Shifts^

A second school of thought suggests that weight loss is due to hormonal disturbances in people with HD. Hormones are the body’s chemical messengers, and are important for regulating physiological processes, like hunger. The hypothalamus secretes many hormones, so when HD causes cells in the hypothalamus to malfunction and die, hormone production is disturbed.

Some of the hormonal signals that the hypothalamus sends out go to the gut and fat tissue, and direct processes like eating and burning energy – processes that are very important in maintaining a healthy weight. Therefore, some scientists think that cell death in the hypothalamus causes hormonal changes that might contribute to weight loss and other problems such as sleep disturbances, as described here.

Dysfunctional Digestion^

Further insights have come from studying the way mutant huntingtin interacts with the digestive system. Certain symptoms of HD have hinted that the disease might affect the gut; apart from weight loss, people with HD often experience nutritional deficiencies, cramps, and wasting of skeletal muscles. People with HD are also prone to gastritis, a disease where the stomach lining becomes irritated or swollen.

Despite these symptoms, many HD researchers have traditionally thought that mutant huntingtin only affected the brain – a belief that struck some as strange because the protein is made and found throughout the body. However, results from a recent study suggest that mutant huntingtin in the gut might interfere with important digestive processes, thus contributing to weight loss.

In the study, van der Burg and colleagues looked at R6/2 mice, which are mouse models of HD described in greater detail here. They noticed several physiological changes that could all impact digestion. First, they noticed that the small intestines of HD mice were 10-15% shorter than those of normal mice, and that they had smaller villi, the tiny finger-like projections in the gut that take up nutrients. On top of that, scientists noticed that the mucus lining of the gut of the HD mice was 20-30% thinner. Since all of these structures are needed for nutrient absorption, these findings suggest that HD mice can’t take up nutrients as efficiently as normal mice.

Furthermore, the group found that the HD mice were missing a few key hormones that control the speed at which food passes through the body. This caused an increase in ‘transit time’: the food passed more slowly through the gut. Longer transit time might foster bacterial growth; if food takes longer to pass through the gut, harmful bacterial have more time and a better opportunity to flourish. This could make the small intestine irritated and inflamed, which could cause malabsorption of nutrients, chronic diarrhea, nausea, bloating, flatus, and weight loss. Those bacteria might also use up nutrients that the body would have otherwise taken up.

To see whether these physiological differences actually have an impact on digestion, researchers then compared the feces of HD mice to those of normal mice. They found that HD mice excreted more of what they ate, suggesting that they absorbed fewer calories and nutrients from their food. Notably, the mice that were the worst at absorbing nutrients from their food lost the most weight.

Van der Burg et al. had a few ideas as to what mutant huntingtin might be doing to interfere with digestion. Since the protein is present in gut cells, it could interfere with cell function and nutrient absorption. They also thought that mutant huntingtin might affect transcription, the process by which DNA is converted into protein as described here. If mutant huntingtin affects transcription in gut cells, it could cause a decrease in levels of important proteins needed for cells to survive and function properly.

While findings in HD mice don’t always translate to humans, these results indicate that scientists might benefit from studying the way HD affects digestion in people. Van der Burg et al. suggest that such research might help doctors improve their understanding of nutritional supplements for HD, and might even change the way we think about how people with HD metabolize and react to medicine.

Solutions^

Weight loss in HD has long puzzled doctors, patients, and caretakers alike. Two popular explanations of the phenomenon – chorea and reduced food intake – have been debunked as major contributors to weight loss. However, scientists have made new in-roads in recent years. By discovering that mutant huntingtin might disrupt energy metabolism, digestion, and hormones in HD mice, scientists have enhanced our understanding of HD, which may pave the way to new treatments and therapies. For example, the hypothesis that weight loss is linked to abnormalities in energy metabolism suggests that energy-boosting drugs – namely creatine and Coenzyme Q10 – are strong candidates to fight HD, as described in these articles here. Each further discovery about HD leads to a greater understanding of the disease, and brings hope for patients and families.

Sources^

1.     Aziz NA, van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T; EHDI Study Group, Roos RA. Weight loss in Huntington disease increases with higher CAG repeat number. Neurology. 2008 Nov 4;71(19):1506-13.

This medium-difficulty study describes how people with more CAG repeats lose more weight – and provides some theories as to why that might be the case.

2.     Djoussé L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight loss in early stage of Huntington’s disease. Neurology. 2002 Nov 12;59(9):1325-30.

This medium-difficulty article describes weight loss in people with early-stage HD

3.     Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J; Huntington Study Group. Rate and correlates of weight change in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):209-12.

This medium-difficulty article describes weight loss in people with early-stage HD

4.     Kremer HP, Roos RA. Weight loss in Huntington’s disease. Arch Neurol. 1992 Apr;49(4):349.

This short, medium-difficulty column suggests that cell death in the hypothalamus could contribute to weight loss

5.     Petersén A, Björkqvist M. Hypothalamic-endocrine aspects in Huntington’s disease. Eur J Neurosci. 2006 Aug;24(4):961-7. Epub 2006 Aug 21. Review

This technical article describes how hormonal changes in people with HD might lead to weight loss

6.     Pollard J, Best R, Imbrigilo S, Klasner E, Rublin A, Sanders G, Simpson W. A Caregiver’s Guide for Advanced-Stage Huntington’s Disease. Huntington’s Disease Society of America, 1999.

This easy-to-read handbook is a very helpful resource for caregivers taking care of people in late-stage HD

7.     Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington’s disease. Ann Neurol. 2000 Jan;47(1):64-70

This study measured movements of people with HD, and found that their total energy expenditure was the same as that of people without the disease, and is somewhat technical

8.     Seong IS, Ivanova E, Lee JM, Choo YS, Fossale E, Anderson M, Gusella JF, Laramie JM, Myers RH, Lesort M, MacDonald ME. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum Mol Genet. 2005 Oct 1;14(19):2871-80. Epub 2005 Aug 22.

This technical article describes how huntingtin interferes with energy metabolism in a CAG-dependent fashion

9.     Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa A, Velásquez L. Assessment of the nutrition status of patients with Huntington’s disease. Nutrition. 2004 Feb;20(2):192-6.

This medium-difficulty paper discusses the result of the study on 25 HD patients that ate an average of 400 calories more than controls each day.

10. van der Burg JM, Winqvist A, Aziz NA, Maat-Schieman ML, Roos RA, Bates GP, Brundin P, Björkqvist M, Wierup N. Gastrointestinal dysfunction contributes to weight loss in Huntington’s disease mice. Neurobiol Dis. 2011 Oct;44(1):1-8. Epub 2011 May 23.

This technical article describes the impact of huntingtin on digestion in HD mice

M. Hedlin 11.16.11

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Advance Directives

In the last stages of Huntington’s disease (HD), patients have difficulty thinking and communicating clearly, so decisions about their end-of-life medical care often fall to doctors and relatives. However, many people with HD have strong opinions as to how they would like their last years to unfold. Advance directives are instructions written by mentally and physically competent patients to convey their preferences about end-of-life medical care ahead of time. They are powerful expressions of a person’s wishes about their future health care. Anyone over the age of 18 is legally qualified to make these decisions for himself or herself. Health care professionals who are caring for a patient will refer to advance directives if the patient is unable to make or communicate their decisions later in life.

Advance Directives and HD^

Why are advance directives important for patients with HD? Because the age of onset and severity of HD symptoms are relatively unpredictable, sudden changes can quickly change the course of patients’ lives. During the end stages of HD, many patients are nonverbal and unable to communicate their wishes. Advance directives allow patients to decide their end-of-life care ahead of time so that their treatment fits their unique mental and emotional needs.

While it may seem like a simple task to address advance directives before late-stage symptoms occur, there are numerous obstacles that make it difficult for patients to make such decisions earlier in their life. These obstacles mostly fall into three categories: the doctor, the patient, and the patient’s family. Regarding doctors, there are currently no guidelines requiring doctors to discuss advance directives with patients early in the course of the disease. Thus, many doctors do not discuss end-of-life care with their patients when they are in earlier stages of chronic diseases. This greatly contributes to the difficulty of the decision process for the patient.

Patients themselves may exhibit cognitive dysfunction, denial, poor judgment, or psychiatric symptoms and thus may not be able to make an informed decision even at early stages of the disease. In early stages of the disease, patients may want to avoid the topic of advance directives, as they have difficulty confronting their declining ability to function as parents, employees, and other roles they fill in their lives. In late stage HD, communication becomes the predominant issue, as patients cannot make their wishes clearly known.

Advance directive decision-making may also be delayed by the dynamics of the family. First of all, once a patient becomes mentally incompetent or is unable to communicate his or her wishes, deciding on who should make these decisions becomes a source of controversy. Furthermore, the family not only has to deal with the shock of a newly diagnosed relative, but also may become increasingly worried about other at-risk individuals. In order to cope, families may be experiencing what medical professionals have deemed denial —a common, short-term protective mechanism for dealing with the shock of diagnosis. If end-of-life care is not discussed early enough, family members may not agree with the patient’s decisions.

Despite the obstacles in addressing advance directives at an early stage of disease, the value of deciding between options for end-of-life care early-on is an important means of ensuring autonomy for HD patients.

Elements of Advance Directives^

Advance directives have several important elements: a health care proxy, a living will, do-not-hospitalize and do-not-resuscitate orders; decisions about tube feeding; and decisions about brain donation for diagnosis and research purposes.

Healthcare Proxy^

A healthcare proxy is a person who makes decisions for the patient once the patient is deemed unable to make those decisions for himself or herself, and is usually a family member of the patient. The healthcare proxy should be an adult over 18 who is mentally, physically and emotionally equipped to make decisions. The healthcare proxy form is approved by law in all states and is a written document. It is very important that a patient’s doctor knows who is appointed health care proxy, and that a healthcare proxy is chosen earlier rather than later.

Living Will^

A living will is a set of instructions to a doctor about treatment and life-sustaining procedures. It is helpful for the patient to discuss living wills with a medical professional to stay informed about the advantages and disadvantages of all types of treatments and procedures. These instructions do not become effective until two doctors certify in writing that the patient is unable to make a healthcare decision. Lastly, the patient can change or revoke advance directive instructions anytime, as long as s/he has the mental capacity/communication abilities to do so.

Feeding Tube^

The wishes of the patient in regards to use of a feeding tube can be stipulated in the advance directive. Feeding tubes are usually used when the patient has no other way to swallow food. They may also be used to provide supplements when the patient can eat but needs to receive more nutrition through the tube. Tube feeding is common in late-stage HD treatment. The tube is made of soft plastic and is usually inserted into the stomach. It can be used to avoid problems such as aspiration, which is when food goes into the lungs instead of the stomach. Aspiration can increase the likelihood of pneumonia, which can cause serious medical complications in HD patients. The advantages of the feeding tube include: 1) ensuring that the body receives essential nutrients, 2) allowing patients to eat foods that they enjoy, 3) ameliorate weight loss, which is a serious health risk for late-stage HD. Disadvantages include: 1) medical risks associated with feeding tube insertion, such as infection or bleeding, 2) not all patients gain weight and feel full while on the feeding tube, 3) vomiting and aspiration can still occur occasionally, 4) potential re-hospitalization if the feeding tube is dislodged. In the end, it is the patient’s decision whether or not he/she would like a feeding tube if he/she is deemed capable of making healthcare decisions—but again, the decision should be discussed early and included in the advance directive if desired, as the patient may not continue to be able to choose for him/herself.

Do Not Hospitalize Order^

A “Do Not Hospitalize Order” (DNO) is one way for patients and families to influence the type of care patients and their families receive, and where the care takes place. During late-stage HD, people may prefer the warmth and comfort of a home, or they may wish to be hospitalized. There are numerous advantages and disadvantages to each choice. Hospitalization allows patients to have more advanced medical care. Physicians can more quickly diagnose and treat patients and have access to specialized equipment that might be needed to treat certain conditions. However, hospitalization is undesirable for some patients because hospital staff is less familiar with the patient and their individual needs. Patients sometimes become anxious in the unfamiliar surroundings, and may dislike the repeated diagnostic tests, such as blood pressure measurements.

Do Not Resuscitate Order^

A “Do Not Resuscitate” (DNR) order is written by the patient’s doctor in consultation with the health care proxy and other family members. This order states that cardio-pulmonary resuscitation (CPR) will be withheld when a person’s breathing or heart stops. When anyone is admitted to a hospital or nursing home, the staff is required by law to perform CPR if and when breathing or the heart stops unless there is a DNR order in effect (3). Like the “do not hospitalize” order, the DNR can be changed at anytime provided that the patient is mentally capable.

Brain Donation^

Brain donation involves donating brain tissue after death so researchers can use it to study HD and other neurodegenerative diseases. Researchers can use brain tissue to directly analyze nerve cells and brain changes due to HD in humans, which is an important step on the path towards better understanding HD and finding treatments that work.

There are several challenges that make brain donation challenging for some individuals.
First, the patient or his/her relatives must agree to donate the brain before the time of death. Second, not all institutions have the resources to pay for brain donation, as it costs between 10,000-30,000 US dollars to collect each brain.

Thinking Towards the Future^

While it may seem a bit overwhelming to face end-of-life care issues at a young age or during early stages of Huntington’s disease, it is extremely important to do so in order to ensure that patients’ true wishes are met even if patients are unable to make or communicate their decisions in the future. There is a lot of information available regarding each of these decisions, and speaking about each of them early on can potentially reduce stress during late-stage HD when family members and health care workers need to be aware of a patient’s desires. Finally, it is important to remember that the advance directive is a “living” legal document and any instructions specified in the document can be changed or revoked at the patient’s discretion at any time, as long as s/he has the mental capacity/communication abilities to do so.

Further Reading (GREAT LINKS!):^

http://www.hdac.org/features/article.php?p_articleNumber=27

http://www.hdny.org/Advance_Directives_Workbook.pdf

http://www.hda.org.uk/download/fact-sheets/HD-ADRT.pdf

Works Cited^

Klager J., Duckett A., et al. Huntington’s Disease, A Caring Approach to the End of Life, Care Management Journals. 9.2 (2008).

This medium-difficulty article describes challenges in end-of-life care, identified in a long-term care facility specializing in Huntington’s disease

Kretzschmar H. Brain banking: opportunities, challenges and meaning for the future. Nat Rev Neurosci. 2009 Jan;10(1):70-8. Epub 2008 Dec 3.

This easy-to-read article describes how brain banking is important for science, and the challenges that stand in the way

Sheila A. Simpson, Late Stage Care in Huntington’s disease, Brain Research Bulletin. 72.2-72.3 (2007): 179-181.

This easy-to-read article describes issues that should be addressed in late stage care for HD.

P. Bakhai, 9.19.11

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Insurance and HD

Healthcare reform has been a hot topic in the United States in recent years, and many important changes are continually being made. In this article, we will take a look at some alterations that are particularly relevant to HD patients and their families. The first half of the article discusses the Genetic Information Nondiscrimination Act (GINA), and how it impacts insurance and employment for individuals who are at-risk for genetic conditions like HD, as well as those who are considering a genetic test. Next, this article covers the new Affordable Care Act, and changes to insurance policies for patients with pre-existing conditions, such as HD.

GINA (Genetic Information Nondiscrimination Act)^

In May of 2008, the updated Genetic Information Nondiscrimination Act (GINA) was signed into federal law. All of its contents came into effect by May 21, 2010.

What does GINA cover?^

GINA is meant to prohibit health insurers and employers from discriminating against anyone based on genetic information. This means that no one can be denied insurance or charged a higher premium based on genetic information, and that health insurance companies cannot request genetic information from any person or their family members. In addition, employers cannot make decisions about hiring, firing, or promotion based on genetic information.

What qualifies as genetic information?^

  • Any genetic tests of an individual, including those done in a research study. A genetic test is formally defined as “an analysis of human DNA, RNA, chromosomes, proteins, or metabolites that detects genotypes, mutations, or chromosomal changes.”
  • Results of a genetic test or record of participation in services such as genetic testing, genetic research, and genetic counseling for an individual’s family members, up to 4th degree relatives
  • Genetic tests of a fetus or embryo, including those conceived through IVF
  • Family history of any genetic diseases or disorders

What is not covered by GINA?^

GINA does not apply to life insurance, disability insurance, long-term care insurance, and employers with fewer than 15 employees.

It is also important to note that GINA is not retroactive, meaning that any decisions made before the law came into effect cannot be challenged. However, any employer or insurer who holds genetic information can no longer use it, even if the information was obtained before GINA existed.

Once someone exhibits symptoms of a genetic disease or disorder, that individual is not covered by GINA. In this case, any insurance or employment decisions made based on the existing condition are legal. For patients at this stage of disease, the Affordable Care Act of 2010 may be relevant.

Affordable Care Act ^

What is the Affordable Care Act?^

Signed in March of 2010, the Affordable Care Act introduces a wide variety of changes to health insurance policies and costs in the United States. Its various components are being implemented independently, so pay attention to when each change becomes law!

What if I have HD and don’t have insurance right now? ^

Under the Affordable Care Act, adults with existing disabilities and mental or physical illnesses cannot be denied health insurance coverage as of January 1, 2014. The same rule has been in place for children since September 23, 2010.

If you are an HD patient, one current option for coverage is the Pre-Existing Condition Insurance Plan (PCIP) in your state. Some states are choosing to operate their own PCIPs, while others are offering federally-run plans.

All legal U.S. residents who have been without insurance for at least six months may apply for PCIP coverage. This also applies to those who have been denied insurance or charged an unaffordable premium in the past due to their condition. Eligibility is not based on income. PCIP covers primary and specialty care, hospital care, and prescription drugs, including any services needed to treat or manage a pre-existing condition. Note, however, that a positive genetic test for HD cannot be considered a pre-existing condition, so individuals with a positive gene test can and should apply for regular insurance programs instead of PCIP.

Currently, because PCIP premium amounts vary from state to state, some patients may need to apply for Medicaid or other assistance programs if PCIP costs are too high. In these cases, all terms and conditions for Medicaid eligibility must be met, regardless of any pre-existing conditions. Gaining better coverage for low-income or unemployed individuals is an ongoing effort, but there has not been significant progress on this front.

What if I have HD and already have insurance?^

If you have had health insurance coverage since September 23, 2010, your insurer cannot unfairly cancel coverage, deny services, or raise premiums, even if your condition worsens and demands expensive treatments or medications. This applies even if you accidentally forgot to mention a symptom experienced or treatment received when submitting your insurance application. Note, however, that intentional omissions, untrue information, and late payments can still be used as reasons to cancel coverage or refuse services.

Lifetime dollar amount limits on essential services have also been illegal since September 23, 2010, and annual limits will be banned for many services after January 1, 2014. If financial hardship or another extenuating circumstance causes you to lose coverage, insurers must provide a 30-day warning before terminating your policy. You will be eligible to apply for PCIP 6 months after the termination.

A new Healthcare Exchange program is currently in the works, and may provide better coverage or lower premium options for patients with pre-existing conditions, such as HD. Many changes have been discussed and considered in Congress over the past few years, so staying informed about the latest developments in healthcare reform is necessary and helpful.

For Further Reading:^

The government’s official guide to the Affordable Care Act
http://www.healthcare.gov/law/introduction/index.html

Full text of the Genetic Non-Discrimination Act of 2008
http://thomas.loc.gov/cgi-bin/bdquery/z?d110:HR00493:

Kaiser Family Foundation’s Guide to Health Reform (very up-to-date)
http://healthreform.kff.org/

S. Liou, 8/30/2011

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Family Planning

Family Planning

The decision to have a family comes with a great deal of responsibility, and many important choices. For people with Huntington’s disease (HD), one of the most pressing considerations in their decision to have children relates to the disorder. People with HD have a 50% risk of passing the disease to their offspring each time they conceive, unless they attempt an alternative method that stops HD from being inherited through the generations. Those “at risk” of HD, who have parents or relatives with the disease but do not wish to be tested to see whether they are affected, also have the potential to pass HD on to their children as they might be HD-positive.

This article outlines a number of reproductive options available to couples that know their HD status, and to those who prefer not to know. There is no easy answer, and each couple may come to a different conclusion based on their personal preferences and system of beliefs. This article provides possibilities: the solutions, however, can only be reached by the individuals themselves.

Decide whether to get tested^

The first decision a couple faces is whether or not the person at risk should get tested for HD; the test results might significantly shape the choices a couple makes in planning their family. For more information on genetic testing, click here, and to learn more about how getting tested might affect romantic relationships, click here. Getting tested is not necessary, as people who are at risk have several ways to avoid passing on HD without finding out their own status, but it might be helpful.

Not having children/Adoption^

Upon learning of their HD-positive or at risk status, some people choose to not have children. Many people that make this choice do so to avoid the risk of passing HD on to their children, expressing guilt at the thought of transmitting the disease (Decruyanaere et al., 2007). Other couples worry they won’t be able to fully raise the child before the HD-affected parent’s symptoms set in, and they don’t want the disease to compromise their parenting (Klitzman et al., 2007). On one hand, couples who don’t have children can rest easy knowing that they will never pass HD on to future generations; on the other, some may regret not having children (Decruyanaere et al., 2007).

Couples that don’t want to remain childless sometimes decide to adopt instead.  Adoption helps a needy child, and allows a couple to raise children without passing on HD. Prospective parents generally work with adoption agencies to help them through the adoption process, and to help them screen children to find the right match. The decision must be weighed carefully, as prospective parents need to consider whether HD will jeopardize their ability to raise children; some adoption agencies might refuse to let HD-positive people adopt on these grounds (Klitzman et al., 2007). For more information about adoption, click here.

Natural Conception^

Many couples choose to have children naturally. If one parent is HD-positive, then the child has a 50% chance of having HD. If one parent is at risk (and therefore has a 50% chance of having the disease), their child has a 25% of having HD – though that number increases to 50% if the at risk parent begins to show symptoms. If both parents have HD, then the child has a 75% chance of having the disease.

Parents who accept these risks and have children naturally often say that their desire to have children outweighs their fears about HD. They acknowledge that their child might inherit the disease, but express hope that a cure for HD may be found in their child’s lifetime; they also point out that even if no cure is found, their child will have many disease-free years, as HD rarely sets in before age 40 (Decruyenae et al., 2007).

Sperm or egg donation/Surrogate mother^

Couples also have the option of sperm or egg donation, depending on which partner is affected by HD. If the prospective father is HD-positive, couples might consider sperm donation, in which a donor’s sperm is inserted into the prospective mother’s uterus or vaginal canal using a syringe. For more information on sperm donation, click here. If the prospective mother is HD-positive, couples can have children through egg donation, in which another woman donates her eggs and they are fertilized with the father’s sperm through in-vitro fertilization (IVF). Alternatively, a couple could consider having a child with a surrogate mother, where the father’s sperm is inserted into a surrogate mother. However, while sperm donation is relatively inexpensive at several hundred dollars, both egg donation and surrogacy cost thousands of dollars; couples in which the prospective mother has HD generally choose other reproductive options instead.

Test Tube Babies: Preimplantation Genetic Diagnosis (PGD)^

Pre-implantation Genetic Diagnosis (PGD) screens embryos for genetic diseases, such as HD, before they are implanted in a woman’s body. This exciting new technology, developed in 1998, allows couples to prevent their children from inheriting genetic diseases that run in the family (Decruyenae et al., 2007).

To generate the embryos used in PGD, the couple must first undergo in-vitro fertilization (IVF). In IVF, a woman’s eggs and man’s sperm are combined in a laboratory. First, some of the woman’s eggs are collected. Since women usually only release one egg every month, doctors give the woman fertility medication to cause her to release many eggs at once, a process called “superovulation”. The eggs are monitored using ultrasound imaging. Once they are mature, the doctors perform a minor surgery. The woman is given local anesthetic, which numbs the area the doctor will be working on, and sedatives, which put her to sleep. Then, using ultrasound, the doctor guides a hollow needle to the ovary and removes the eggs.

The eggs are then fertilized using the man’s sperm. This is the step that earned this procedure the name “in vitro fertilization”: “in vitro” is Latin for “in glass”, referring to the fact that the fertilization is performed in test tubes or petri dishes, rather than in the body –which gave  rise to the term “test tube babies”. The sperm and egg combine to form a single-celled embryo, which grows and divides. For more information on IVF, click here.

Once the embryo has reached the 8-cell stage, PGD is performed. One of the eight cells of the embryo is removed for testing. This procedure is harmless, as the embryo is still composed of stem cells, and can easily grow to replace the lost cell. Since every cell has a complete copy of the genetic code, any one cell will suffice for genetic testing. At this point, a “genetic diagnosis” is carried out on the cell. However, geneticists can’t use the same test that is used to check adults for the HD allele, as one cell isn’t enough to test for CAG repeats directly (a process described here). Instead, scientists take blood samples from both prospective parents, and from the parents of the at-risk individual. They then look at the genes right next to the HD allele, and choose a “marker” – a unique fingerprint of DNA that differs between the chromosome with the HD allele, and those without. Since genes that are close together are almost always inherited together, the embryos with the HD allele will also have this particular marker. Therefore, an embryo that tests positive for the marker is considered “affected”; it carries the HD allele, and is expected to have HD. Embryos that do not carry the marker are “unaffected”, and are considered for implantation (Sermon et al., 2002).

The doctor will then implant between 1-4 embryos. Usually, more than one embryo is implanted, to increase the chances of a successful pregnancy. If the first implantation process fails, and there are enough unaffected embryos remaining from the egg retrieval process, the doctor can simply perform a second implantation. However, if there aren’t enough unaffected embryos remaining, the woman will have to begin the entire process again, starting from egg retrieval.

To summarize, the woman undergoes egg retrieval in which several eggs are collected. Those eggs are fertilized with the man’s sperm through IVF, and allowed to divide to the 8 cell stage. PGD is performed on one cell of each embryo, and the embryos that are HD-free are selected for implantation. This process, while complicated and expensive, virtually ensures that the children of a PGD-tested couple will be HD-free – the only risk of the child having HD would come from human error, and is extremely small.

PGD comes with a handful of medical risks. As multiple embryos are implanted, some women end up having more than one child. Some may be happy with this result, but others might have a more difficult pregnancy. Another problem – ovarian hyperstimulation syndrome – is caused by an over-reaction to the fertility medication used. The problem, which causes symptoms such as diarrhea, nausea, and dizziness, can be solved by drinking more water. Other complications, such as infections acquired during surgery, are treated with antibiotics. For a full discussion of risks, click here.

Non-disclosing PGD^

An alternative form of PGD exists for those who don’t wish to be tested. As with disclosing PGD, IVF is performed to create embryos, and doctors perform PGD to determine which are affected, and which are HD-free. The difference between disclosing and non-disclosing PGD is that the doctor never reveals the at-risk parent’s status: the parents do not find out how many embryos were affected (if any), and do not know how many embryos were implanted.

Non-disclosing PGD brings up a number of weighty issues. First, the doctor knows the status of the at-risk parent, but must keep it a secret. Even if the news is good – if none of the embryos have HD, the parents are almost certain to be HD-free – the doctor can’t reveal the parent’s status, as this would compromise secrecy for other clients; clients who were not congratulated would know their HD-positive status by default (Braude et al., 1998).

Second, if the parent is a carrier, and all embryos are affected, then a “mock transfer” is carried out; the doctor performs an implantation in which no eggs are implanted. This ensures that the person doesn’t find out his or her HD-positive status. Some countries, such as Holland, consider this an unnecessary medical risk, and therefore require the at-risk individual to be tested before undergoing PGD (Asscher and Koops, 2010).

Third, half of the couples that choose non-disclosing PGD are perfectly healthy, and therefore undergo IVF-PGD when they could simply have a natural pregnancy. Again, this factored into Holland’s decision to force couples to get tested before resorting to PGD, as half of the couples will avoid the cost and medical risks of IVF-PGD. However, the US and most other countries have no such policy, and non-disclosing PGD is accepted and performed (Asscher and Koops 2010). For a discussion of the right not to know, click here.

In short, PGD allows couples to have children that will be HD-free. The procedure, admittedly, is physically and emotionally draining, particularly because the success rate is currently around 20%; a couple may have to undergo multiple rounds of IVF-PGD for a successful pregnancy (Sermon et al., 2002). Furthermore, with a price-tag of $9,000-$18,000, this procedure might be out of reach for some couples, particularly if their health insurance companies refuse to subsidize the cost. However, many HD-positive or at-risk couples have had successful pregnancies through IVF-PGD. For an account of an HD-positive mother who had twins through IVF-PGD, and successfully lobbied her health insurance company to cover most of the expenses, please click here.

Testing the Fetus: Prenatal Diagnosis^

Another option exists for women who are already pregnant: Doctors can perform a prenatal diagnosis, in which the fetus is tested for HD. As with PGD, this procedure can take two forms: HD-positive people undergo a “disclosing” prenatal diagnosis, and people who are at-risk but do not wish to be tested can have “non-disclosing” prenatal diagnosis, in which their fetus is tested for the risk of HD and the parent’s status remains unknown.

Prenatal diagnosis can be performed through chorionic villus sampling (CVS) or amniocentesis. In both, a needle is guided by ultrasound imaging to collect a sample of cells for genetic testing. In CVS, the needle is inserted into the uterus through the vagina, and collects a few cells from the placenta, the organ that develops alongside the fetus and supplies it with oxygen and nutrients from the mother. CVS is usually performed 10-13 weeks after the mother’s last menstrual period. Amniocentesis is performed later, around 14-20 weeks into the pregnancy. In amniocentesis, a needle is inserted through the abdomen into the uterus and takes a sample of amniotic fluid – the fluid surrounding the fetus – for genetic testing. Both CVS and amniocentesis are very safe procedures, though there is a very small increase in risk of miscarriage. For more information on CVS, please click here, and to read more about amniocentesis, please click here.

Once those samples are taken, genetic tests are performed. For a disclosing prenatal diagnosis, doctors determine the number of CAG repeats the fetus has in its Huntington gene, as described here. If the fetus has 35 or fewer CAG repeats, it is considered HD-free; with 40 or more CAG repeats, it is considered HD-positive; with 36-39, the fetus has an uncertain prognosis, and may or may not develop HD in its lifetime.

If the parent is at-risk for HD, but does not wish to know their status, a non-disclosing prenatal diagnosis is performed through “exclusion testing”. In exclusion testing, the CAG repeats are not directly measured; instead, doctors look at “linked markers” to see which parent the fetus inherited its genetic material from, as previously described in the PGD section of this article. In this method, the couple must get in touch with their parents to collect small blood samples for testing. For the HD-positive parent of the “at-risk” person (the “grandparent” of the fetus), the doctors find markers for the Huntington gene. The doctors consider the fetus at risk of developing HD if either of the affected grandparent’s copies of the Huntington gene are present in the fetus; the grandparent’s HD allele, as well as the grandparent’s non-HD allele, both cause the fetus to be deemed “high-risk”. Therefore, there is a 50% chance that the fetus will have HD if it is marked as high-risk.

After a few weeks, the parents obtain their results. If the fetus is HD-free, the parents can rest easy; the child won’t suffer from the disease, and will never pass HD on. Unfortunately, some parents will receive upsetting results from the genetic test, and have a difficult choice to make.

Parents who are informed that their fetus has HD sometimes choose to keep the child, and do so for a number of reasons. Some say their desire for a child outweighs their fears about HD; others point out that the child will have many disease-free years before symptoms begin; still more express the hope that a cure for HD may be found in their child’s lifetime (Decruyenae et al., 2007). Views on abortion also play a large part in many people’s decisions; for some, their opposition to abortion outweighs their desire to prevent HD from being passed on to their children. A handful of parents don’t believe the results of a prenatal diagnosis should be grounds for abortion because they consider this the first step down a slippery slope towards a eugenic society, in which we begin choosing traits for our children (Klitzman et al., 2007).

All of these concerns are valid points, and deserve careful contemplation. However, most couples that learn that their fetus is HD-positive decide to terminate the pregnancy (Decruyenae et al., 2007). These parents often say they would feel unethical bringing an HD-positive fetus to term, as they don’t wish to subject a child to the difficulties they themselves have undergone (Klitzman et al., 2007).

The decision becomes even more difficult for parents who choose a non-disclosing prenatal diagnosis, and learn that their child is “high-risk”. While the fetus has a 50% chance of being HD-positive, there is still a 50% chance that the fetus is HD-free. For this reason, some countries, such as France, make it very difficult for a woman to have an abortion on the grounds of a non-disclosing prenatal diagnosis (Sermon et al., 2002).

This decision is difficult to make, and parents will have to weigh many personal, moral, and religious considerations; this article only scratches the surface of factors that might take a part in the choice. Some parents choose to avoid prenatal diagnosis entirely, as they don’t wish to risk the psychological and physical burden of abortion (Decruyenae et al., 2007). Ideally, a couple should discuss these issues with a genetic counselor; if possible, counseling should begin before the couple conceives, especially for non-disclosing prenatal diagnosis, as it may take longer than expected for doctors to find useful linked markers for the test.

Conclusion^

Despite the difficulties of living with an inheritable disease, prospective parents should not feel limited by their HD-positive or at-risk status; those who wish to have children have many options, many of which prevent the passage of HD. This decision involves difficult choices, where a couple must weigh personal moral, ethical, and religious beliefs, while taking into account the opinions of family members and close friends. The end result, however, is well worth the work.

Bibliography^

1.     “Amniocentesis : American Pregnancy Association.” Promoting Pregnancy Wellness : American Pregnancy Association. American Pregnancy Association, Apr. 2006. Web. 25 June 2011. <http://www.americanpregnancy.org/prenataltesting/amniocentesis.html>.

This is an easy-to-read website with an in-depth discussion of amniocentesis, going into how the procedure is done, and any risks that might be involved.

2.     “Chorionic Villus Sampling: CVS.” Promoting Pregnancy Wellness : American Pregnancy Association. American Pregnancy Association, Apr. 2006. Web. 17 June 2011.

This is an easy-to-read website with an in-depth discussion of CVS, going into how the procedure is done, and any risks that might be involved.

3.     Asscher E, Koops BJ. The right not to know and preimplantation genetic diagnosis for Huntington’s disease. J Med Ethics. 2010 Jan;36(1):30-3

This is an easy-to-read paper on the ethics of non-disclosing PGD and non-disclosing prenatal diagnosis

4.     Braude PR, De Wert GM, Evers-Kiebooms G, Pettigrew RA, Geraedts JP. Non-disclosure preimplantation genetic diagnosis for Huntington’s disease: practical and ethical dilemmas. Prenat Diagn. 1998 Dec;18(13):1422-6. Review.

This article explores some of the ethical considerations that non-disclosing prenatal diagnosis and non-disclosing PGD bring up, and could be useful for at-risk individuals.

5.     Decruyenaere M, Evers-Kiebooms G, Boogaerts A, Philippe K, Demyttenaere K, Dom R, Vandenberghe W, Fryns JP. The complexity of reproductive decision-making in asymptomatic carriers of the Huntington mutation. Eur J Hum Genet. 2007 Apr;15(4):453-62. Epub 2007 Jan 24.

This is an easy-to-read study looking into the reproductive decision-making process of couples who know their HD-positive status.

6.     Klitzman R, Thorne D, Williamson J, Chung W, Marder K. Decision-making about reproductive choices among individuals at-risk for Huntington’s disease. J Genet Couns. 2007 Jun;16(3):347-62.

This is an easy-to-read study looking into the reproductive decision-making process of couples that are at-risk, but do now wish to be tested.

7.     Sermon K, De Rijcke M, Lissens W, De Vos A, Platteau P, Bonduelle M, Devroey P, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis for Huntington’s disease with exclusion testing. Eur J Hum Genet. 2002 Oct;10(10):591-8.

This technical paper describes how PGD is performed.

8.     “What Are the Risks of PGD Treatment?” Guy’s and St Thomas’ Centre for Preimplantation Genetic Diagnosis. Centre for Preimplantation Genetic Diagnosis, 18 May 2009. Web. 29 June 2011. <http://www.pgd.org.uk/whatispgd/risks/pgdrisks.aspx>.

This easy-to-read website that discusses the medical risks of PGD.

M. Hedlin, 7.20.11; recorded by B. Tatum, 8/21/12

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About Lifestyle and Huntington's Disease

Even when a person is at risk for developing HD there are many things he or she can do about it. Yes, everyone with the HD allele allele will eventually display symptoms of HD. However, the expression of these symptoms is subject to great variability. For example, studies of the HD population in Venezuela revealed that there is great variability in the age of onset (the age at which symptoms first appear) of HD. While the number of repeats of the CAG codon is the most important factor in determining age of onset, it is not the only factor. There may be a big difference in the age at which two individuals with the exact same repeat length-and even genetically identical twins-begin expressing symptoms of HD. Researchers found that, after controlling for repeat length, about 60% of the variance in age of onset is environmental (“variance” is a statistical measure of variability). This important finding means that genes do not completely determine the expression of HD: the environment plays an important role. The implication is that everyday practices regarding diet, exercise, and stress management can greatly influence the onset and progression of HD. While these practices are by no means “cures” or even treatments for HD, they do promote health. Also, it is important to realize that while a correlation may exist between such practices and good health, and even improvement in HD symptoms, that correlation does not mean that the practices are themselves causing the good results. Other factors may be involved. In any event, it is important to consult your medical doctor before making any drastic changes in your lifestyle.

General health promotion strategies address the mental, physical, spiritual, and social connections of who we are and how we live. Through both action and inaction people make choices about their health on a daily basis. Each of us has general health strategies that we are implementing all the time. Taking a moment to look at what your own health strategies are–giving them names, refining them, and exploring ways to improve them–is the very foundation of health. In the big picture, people who proactively address health on all fronts have a tendency to do better than people who do not. The purpose of this chapter is to provide information about life practices that promote general health, and to explore how these life practices may affect the way that individuals respond to HD. Despite the fact that people with the HD allele will eventually show symptoms, the expression of these symptoms can be greatly influenced by the lifestyle choices that those individuals make.

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Diet and Neurogenesis

A novel track of research has unearthed new meaning to the old adage “you are what you eat”. Research suggests that our diet plays a role in neurogenesis, the process by which we produce new neurons. Therefore, a diet rich in “brain food” may promote neurogenesis and thereby might repair some of the damage brought on by Huntington’s disease (HD).

Neurogenesis and HD^

The old myth that a person is born with as many neurons as he would ever have has recently been overturned. Though neurogenesis is most abundant before birth, scientists have shown that adults can make new neurons throughout life. This allows our brains to age gracefully, as these new neurons work to replace the neurons that inevitably die. Neurogenesis allows us to have flexible brains throughout life, which is critical for learning new skills (Greenwood and Parasuraman, 2010). For more information on neurogenesis, click here.

In particular, neurogenesis is important in the context of HD. Neurogenesis continues to occur in HD patients and, in fact, increases as the disease progresses. This increase is thought to be the brain’s attempt to repair itself in response to the widespread neuronal death caused by the disease. However, neurogenesis does not happen fast enough to counter the damage incurred (Taupin, 2008).

It is possible that a diet that promotes neurogenesis could help counter some of the deficits experienced by HD patients. Some scientists have explored how diet can impact neurogenesis, and have found a number of nutrients and dietary regimes that may play a role.

Dietary Restriction^

One major track of research on diet and neurogenesis focused on dietary restriction (DR). DR is a strategy wherein calories are limited to about 70% of the normal diet (Levenson and Rich, 2007). This calorie reduction has been shown to lengthen lifespan; the lives of rats and mice can be extended by as much as 50% if they are put on a restricted diet at a young age, and maintain that diet throughout life. In rats and monkeys, DR helps protect against age-related diseases, like cancer, diabetes, and cardiovascular disease (Mattson et al., 2004)

Scientists think DR brings about these beneficial effects by conditioning cells to be better at protecting themselves. DR is a mild stress that puts cells on the defensive, and causes them to start expressing protective genes and stockpiling useful proteins. Therefore, cells stressed by DR are better able to cope with further stressors. For more information on DR, click here.

One stressor that occurs in many neurodegenerative conditions, like Alzheimer’s, Parkinson’s, and HD, and can be ameliorated by DR, is oxidative stress. In HD, oxidative damage occurs when injured neurons release free radicals, which go on to damage neurons around them (Mattson et al., 2004). For more information on oxidative damage, click here. Therefore, DR may help patients with neurodegenerative diseases by causing neurons to fortify themselves, which could prepare them for the stress caused by HD.

Scientists also believe that DR can help patients with neurodegenerative conditions by promoting neurogenesis. DR increases adult neurogenesis in young adult rats, and reduces age-related declines in neurogenesis in older mice (Levenson and Rich, 2007). Furthermore, DR stimulates neurogenesis in the hippocampus, a brain region important for memory. DR also causes an increase in levels of BDNF, a protein shown to help newly born neurons survive (Mattson et al., 2004). For more information on BDNF, click here. Researchers have found that DR can improve the symptoms of HD and several other neurodegenerative conditions in mice. When rats were injected with a chemical that causes brain damage, the rats kept on a restricted diet were more resistant to the chemical’s neurodegenerative effects, and showed fewer learning and memory problems (Mattson et al., 2004). When HD mice were kept on a restricted diet, they showed less striatal neuron death, it took longer for movement problems to arise, and the mice lived longer (Mattson et al, 2004). So DR may protect against neurodegenerative conditions by stimulating neurogenesis and causing neurons to fortify themselves.

DR, however, is a drastic strategy: it takes tremendous willpower to limit calories to 70% of the normal diet. Furthermore, DR is difficult to implement properly; there is a risk of starvation if the diet is unbalanced, which can have wide-ranging consequences. Luckily, similar effects to DR have been found in mice by simply increasing the amount of time between meals (Stangl and Thuret, 2009).

Some scientists have attempted to harness the beneficial effects of DR through resveratrol, a chemical found in red wine. Resveratrol mimics many of the effects of DR, and is thought to work through the same biological pathways (Greenwood and Parasuraman, 2010). For more information, click here.

So DR and resveratrol may promote neurogenesis, and in this way might protect against the brain damage found in HD.

Dangers of a High-Fat Diet^

Conversely, researchers have also studied situations where cells have too many calories, and have found that neurogenesis is impaired. Mice on a high-fat diet have lower levels of BDNF in the hippocampus, and decreased neurogenesis in a particular area of the hippocampus called the dentate gyrus (Park et al., 2010). Furthermore, when injected with a chemical that injures the brain, mice fed a high-fat diet experienced much more damage than those fed a normal diet. Diets high in fat also decrease the learning and cognitive capabilities of rats (Greenwood and Prasuraman, 2010). Thus, experiments on rodents consistently show that a high-fat diet is unhealthy for the brain.

Vitamins, Nutrients, and Foods that promote Neurogenesis^

Another line of research on diet and neurogenesis has investigated the effect of dietary nutrients on the birth of new neurons. Several antioxidants, such as flavonoids, vitamin E, and curcumin, increase neurogenesis in rodent brains. Antioxidants are chemicals that prevent damage from free radicals, and thus might promote neurogenesis by protecting new neurons, among other things (Gómez-Pinilla, 2008). Flavonoids, found in cocoa and blueberries, are chemicals that increase neurogenesis in the hippocampus of stressed rats, possibly by increasing levels of BDNF (Stangl and Thuret, 2009), and/or by improving blood flow to the brain, which can increase hippocampal neurogenesis (Spencer, 2009). Vitamin E, abundant in vegetable oils, nuts, and green leafy vegetables, aids neurological performance in aging mice (Gómez-Pinilla, 2008). Curcumin, found in yellow curry spice, may increase neurogenesis in the hippocampus of rodents by activating certain cell signaling pathways known to increase neurogenesis and decrease stress responses (Stangl and Thuret, 2009). For more information on curcumin, click here.

Another antioxidant, found in green tea, goes one step further than the others. The chemical (-)-epigallocatechin-3-gallate (called EGCG) promotes neurogenesis in the hippocampus (Yoo et al., 2010), and has been shown to reduce the damage from oxidative stress in other neurodegenerative diseases (Ehrnhoefer et al., 2006). When flies with a form of HD were treated with EGCG, their control over their movements improved (Ehrnhoefer et al., 2006). EGCG might also directly fight the damage of HD, as it has been shown to slow the rate at which the mutant form of the huntingtin protein forms the plaques that are thought to hurt the brain (Ehrnhoefer et al., 2006).

In addition to antioxidants, other nutrients have also been shown to play a role in neurogenesis. Omega-3 fatty acids, present in fish and flaxseed, might also promote neurogenesis, and have been shown to decrease cognitive decline seen with aging and neurodegenerative diseases such as Alzheimer’s (Yurko-Mauro et al, 2010). For more information, click here. Vitamins might stimulate the birth of new neurons since, in some cases, vitamin deficiency can inhibit neurogenesis. For example, deficits in zinc inhibit neurogenesis in the hippocampus of rodents. Zinc, a vitamin essential for normal brain development, promotes the survival and proliferation of neural stem cells, which are the main cell type capable of generating neurons (Adamo and Oteiza, 2010). Therefore, zinc deficiency inhibits neurogenesis in the hippocampus of rodents. Similarly, a deficiency of retinoic acid, a metabolite of vitamin A found in animal foods such as milk, inhibits hippocampal neurogenesis (Stangl and Thuret, 2009).

Altogether, research on diet and neurogenesis is not conclusive. It is difficult to study nutrients effectively: studying a nutrient in isolation ignores many of the complex interactions the nutrient may have in the body. However, there are a few relatively consistent messages that emerge. A vitamin-rich, low-fat diet aids neurogenesis in experiments with rodents, and a low-calorie diet mitigates the effects of neurogenerative disease in mice. As for humans, this diet has not been shown to directly help neurogenesis or ameliorate the problems of HD (Huntington Study group, 2008; Block et al., 2011), but healthy diets have a vast number of other physical and mental benefits: longer life, elevated mood, and higher energy levels, to name a few. In conclusion, eating healthy might promote neurogenesis – but even if it does not, a healthy diet certainly will not hurt.

For Further Reading^

Adamo AM, Oteiza PI. Zinc deficiency and neurodevelopment: the case of neurons. Biofactors. 2010 Mar-Apr; 36 (2) :117-24

A technical paper that discusses the impact of zinc deficiency on the brain

Block RC, Dorsey ER, Beck CA, Brenna JT, Shoulson I. Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol. 2010 Jan-Feb;4(1):17-23. Review

A technical paper that discusses Omega-3 fatty acids and their effects on HD.

Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL. Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci U S A. 2003 Jul 22; 100 (15) :9023-7.

A technical paper that discusses neurogenesis in an HD brain

Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, Legleiter J, Marsh JL, Thompson LM, Lindquist S, Muchowski PJ, Wanker EE. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington’s disease models. Hum Mol Genet. 2006 Sep 15;15(18):2743-51. Epub 2006 Aug 7.

A technical paper that describes how EGCG, an antioxidant found in green tea, may change the way that the mutant huntingtin protein forms harmful plaques

Greenwood PM, Parasuraman R. Neuronal and cognitive plasticity: a neurocognitive framework for ameliorating cognitive aging. Front Aging Neurosci. 2010 Nov 29; 2:150.

A technical paper that discusses strategies to counter the neuron damage that accompanies aging, such as education, exercise, dietary restriction, and a low-fat diet, and goes into research that has been performed on rodents.

Gómez-Pinilla, F. Brain foods: the effects of nutrients on brain function. Nature Reviews Neuroscience. 2008 Jul. Review; 9:568-578.

A technical paper that discusses how various nutrients affect brain function.

Huntington Study Group TREND-HD Investigators. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study. Arch Neurol. 2008 Dec;65(12):1582-9.

Levenson CW, Rich NJ. Eat less, live longer? New insights into the role of caloric restriction in the brain. Nutr Rev. 2007 Sep; 65 (9) :412-5.

A paper that discusses the impact of caloric restriction on the brain in rodents

Park HR, Park M, Choi J, Park KY, Chung HY, Lee J. A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci Lett. 2010 Oct 4; 482 (3) :235-9.

A technical paper that discusses the impact of a high-fat diet on rodents

Mattson MP, Duan W, Wan R, Guo Z. Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx. 2004 Jan; 1 (1) :111-6.

A technical paper that discusses dietary restriction and its effect on the brain in rodents

Spencer JP. Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc. 2010 May; 69 (2) :244-60.

A technical paper that discusses the impact of flavonoids on the brain

Stangl D, Thuret S. Impact of diet on adult hippocampal neurogenesis. Genes Nutr. 2009 Dec; 4 (4) :271-82.

A technical paper that discusses the science behind various dietary strategies and nutrients that have an impact on neurogenesis in the adult hippocampus

Taupin P. Adult neurogenesis, neuroinflammation and therapeutic potential of adult neural stem cells. Int J Med Sci. 2008 Jun 5; 5 (3) :127-32.

A technical paper that discusses neurogenesis and neural stem cells

Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M; MIDAS Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010 Nov;6(6):456-64.

A technical paper that discusses how Omega-3 fatty acids may aid patients with neurodegenerative conditions

Yoo KY, Choi JH, Hwang IK, Lee CH, Lee SO, Han SM, Shin HC, Kang IJ, Won MH. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res. 2010 Jul;24(7):1065-70.

A technical paper that discusses how EGCG enhances neurogenesis

M. Hedlin 6/17/2011

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Genetic Testing

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Individuals at risk for Huntington’s disease (HD) have the option of undergoing genetic testing, which detects the presence or absence of the genetic sequence that causes HD. The decision of whether or not to undergo genetic testing is intensely personal, with many factors to consider. This chapter will provide scientific background information regarding genetic testing for Huntington’s disease.

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Sleep and HD

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Sleep-and-HD

Humans spend an extraordinary amount of their lives asleep. If you sleep eight hours every night, you will have spent one third of your entire life sleeping. But like coffee or cell phone reception, sleep is one of the most basic aspects of everyday life that you probably take for granted—when you are well-rested, you probably do not think about sleep much, but after you have pulled an all-nighter (or two), you are likely to have a keen perception of your body’s intrinsic drive to go to sleep. Although the necessity of sleep is intimately known, the scientific understanding of sleep is still very much incomplete. Scientists know that sleep is common to a wide range of organisms from the very complex, like humans, to the very simple, like worms. The shared need for sleep across distant branches of the evolutionary tree suggests that sleep serves some basic purpose.  However, scientists still have yet to answer many fundamental questions about sleep: Why do organisms need to sleep? What are the molecular and cellular mechanisms that underlie sleep? What are the genes that contribute to sleep disorders?

The importance of sleep^

Experiments in animal models have suggested that sleep is necessary for the survival of a great variety of different organisms. Multiple studies have shown that rats deprived of REM sleep (see next section) die within four to six weeks, while those completely deprived of sleep only survive two to three weeks. Sleep deprivation had a marked physical effect on these rats. The animals that were not allowed to sleep exhibited increased weight loss, decreased body temperature, impaired immune systems, progressive hair discoloration, and the appearance of skin lesions. But even with these obvious signs of deterioration, scientists still were not able to pinpoint the exact cause of death in these sleep-deprived rats. Although scientists could correlate the rapid deterioration of these animals to their total sleep deprivation, they could not identify a distinct chemical or physiological abnormality that ultimately doomed these rats.

Despite the dramatic effects of sleep deprivation in rats, similar physiological symptoms under laboratory conditions have not been observed in humans, as equivalent tests cannot be run on human subjects. Regardless, sleep loss does have recognizable and measurable effects on human cognitive function, motor performance, and mood. These negative effects can be dangerous, especially when sleep deprived individuals are engaging in attention-dependent activities such as driving, medical care and similar tasks that require critical thinking and reasoning. Sleep deprivation also impairs higher brain functions, including memory formation, verbal fluency, and creativity.  The effects of sleep deprivation can be powerfully seen in fatigue-related car accidents. For example, truck drivers who have been on the road for thirteen hours straight are fifteen times more likely to have a fatal car crash in the thirteenth hour than the first hour. In fact, many researchers have suggested that the effects of driving while sleepy can be comparable to driving when drunk. Not getting enough sleep on a consistent basis can result in the buildup of a sleep “debt” that will negatively impact attention, performance, and health.

What happens during sleep^

There is a common conception that sleep is for rest, a period during which the mind and body can rejuvenate after a hard day’s work. This assumption is not unfounded—during sleep, humans are less responsive and less mobile, not dissimilar to other states of unconsciousness such as coma (but unlike comas, sleep is rapidly reversible). However, sleep is a time of significant brain activity that can be observed using a machine known as an electroencephalogram (EEG). By hooking up many different electrodes to the scalp of a patient, researchers can measure the electrical activity that takes place in the brain during sleep. Sleep is also measured by observing eye movements, which closely correlate to the type of brain waves observed in the EEG.

The two main states of sleep have been defined as non-rapid eye movement (NREM) and rapid eye movement (REM). During NREM sleep, neuronal activity in many parts of the brain is decreased, and the waves that appear on the EEG are characteristically slower than waking states. In addition, this sleep stage is accompanied by noticeable physiological changes, including the increased secretion of growth and sex hormones and decreased motor activity, heart rate, metabolic rate, breathing rate, blood pressure and intestinal mobility. Conversely, scientists have found that during REM sleep, brain waves are similar to those observed when humans are awake. This raises the interesting question: if neuronal activity is so similar in periods of both REM sleep and wakefulness, what accounts for the drastic differences between these two states? It has been suggested that a small number of neurons are responsible for differentiating between REM sleep and waking. REM sleep is characterized by pupil constriction and rapid movement of the eyes. Accompanying physiological responses include irregular heart rate, breathing and blood pressure. In addition, REM sleep is also when human dreams occur, which have been described as intense bursts of activity in certain populations of neurons. Throughout the night, the brain will alternate between periods of REM and NREM sleep every 90 minutes, repeating this cycle five to six times every night. Although both REM and NREM periods will occur during this 90 minute time window, the proportion of REM to NREM sleep increases during the night. NREM sleep dominates just after falling asleep, while periods of REM sleep dominate in the later sleep cycles.

Despite the well-characterized neurological and physiological changes that occur during sleep, scientists are still in disagreement over the actual purpose of both NREM and REM sleep in humans. Current theories include: reducing the energy consumption of the brain, consolidating memory, promoting neural plasticity (for more information on neural plasticity, click here), and increasing the body’s synthesis of important cellular building blocks such as proteins. Even though there have been many experiments showing that sleep is correlated with these various functions, scientists have found it very difficult to develop a unified theory of why we sleep. Part of this can be attributed to weaknesses in the empirical evidence—even if certain effects are statistically significant, they are not particularly notable. For example, although research has shown that exercise can improve sleep, this is only by about 10 minutes per night.  In addition, sleep research is conducted with a variety of different methods in a variety of organisms, further confounding efforts to build a unified theory of sleep. After all, the chemistry, physiology and function of sleep could very well differ significantly between similar organisms.

Sleep and circadian rhythm ^

You probably know from experience that your body responds differently depending on the time of the day. For example, you likely find it much easier to fall asleep at night than in the middle of the day. This is because darkness activates your body’s production of melatonin, a hormone that promotes sleep. Indeed, the entire human body runs on a 24-hour cycle of wakefulness and sleep. This so-called circadian rhythm (circa-, “approximately,” –diem, “day”) is driven by pacemaker cells in the hypothalamus, the part of your brain that controls a range of vital functions, including hunger, thirst, blood pressure and body temperature. Your circadian rhythm not only controls when you are alert and when you are tired, but it also coordinates your body’s countless chemical reactions. For example, during the day, when your blood sugar levels are likely to be high from eating, your body activates the chemical reactions that break down sugar into stored energy. Conversely, during the night, when your blood sugar is likely to be low, the specific processes that create sugar from stored energy are activated. The effects of the circadian pacemaker can also be seen at a whole-organism level. Human alertness and performance is highest during the day and lowest in the hours before daylight (3:00 – 6:00am), correlating with the time that humans are likely to be awake and asleep. Additionally, immediately after waking, you have probably experienced a good period of time when you were groggy and not alert. This span of time is known as sleep inertia and can last for hours after you get up. In opposition to this sleep inertia, the circadian clock sends out wake-promoting signals throughout the day, which counteracts the propensity to go back to sleep. The opposite process happens at night, with sleep-inducing signals eventually overpowering the wake-promoting ones, resulting in sleep. This natural cycle of sleep/wake signals, driven by the circadian rhythm, explains why humans tend to sleep more efficiently at night and less efficiently during the day.

It is becoming clearer that when you sleep may be just as important as how much you sleep. Deviating from your body’s circadian rhythm can lead to neurological and physical problems. Research has shown that shift workers with jobs that require them to be awake at night (e.g. police officers, fireman and health care providers) are more likely to suffer from diminished performance, sleep issues, and stress-related disorders than those who work during the day. The latter two problems can lead to more-serious conditions such as high blood pressure, stroke and heart disease. Indeed, a report by the International Agency for Research on Cancer has concluded that shift work puts individuals at a higher risk for cancer, which may be a consequence of the cellular effects of circadian rhythm disruption.

Sleep disruption and Huntington’s disease ^

Given HD’s devastating effects on many different regions of the brain, it is perhaps unsurprising that the disease would have an effect on sleep. Although the striatum, the part of the brain most visibly affected by the disease, is not currently thought to play a large role in sleep regulation, Huntington’s disease does affect several regions that have been directly implicated in controlling sleep.  For example, patients with HD have been shown to have significant atrophy of neurons in the hypothalamus, a region of the brain intimately involved in regulating metabolism and sleep/wake cycles. It is also possible that the sleep disturbances of patients with HD are secondary effects of other disease symptoms, such as depression and anxiety.

One survey on HD and sleep performed in Britain found that 87.8% of respondents suffered from sleep problems, including restless limb movements, jerky movements, waking during the nighttime, early waking, and sleepiness during the day. These harmful symptoms have been correlated with many measurable sleep abnormalities. In a study performed by an international group of scientists, individuals with HD underwent nighttime sleep monitoring and daytime wakefulness examinations. These tests used a variety of instruments to measure sleep cycle progression, eye movements, brain activity and other physical indicators of sleep. When compared to the control group, individuals with HD spent more time in the light sleep stages (stages 1-2), experienced more periodic leg movements, and generally had lower sleep efficiency, the number of minutes spent in sleep divided by the number of minutes spent in bed. In addition, individuals with HD have been shown to generally spend less time in REM sleep. Studies have shown that the long-term deprivation of REM sleep results in symptoms similar to those seen in acute sleep deprivation—impaired cognition, unstable moods and hormonal imbalances. These effects on REM sleep have been observed in individuals that were pre-symptomatic or otherwise had very mild symptoms, suggesting that problems with REM sleep are an early indicator for HD. It is noteworthy that other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s, show similar sleep disturbances, suggesting that these illnesses may have similar effects on the neural networks that regulate sleep.

Because of the many detrimental effects of sleep deprivation on human health, scientists believe that the sleep disturbances associated with HD can exacerbate the disease. Indeed, many of the symptoms of sleep disorders are the same as the symptoms of Huntington’s disease, including the loss of motor control, memory problems, mood changes, and impaired cognitive function. Thus, disturbed sleep may be one of the mechanisms through which the behavioral, cognitive, and motor problems associated with HD develop. It is even possible that sleep deprivation is primarily responsible for some of the symptoms of HD, a hypothesis which remains to be tested. This raises the interesting possibility that treating sleep problems can improve the lives of those with HD. Research in R6/2 mice, a transgenic mouse model for HD, has shown that regulating the sleep of affected mice significantly improves their cognitive abilities. In these studies, affected mice were given a sedative to help them fall asleep during the day, and then a wake-promoting drug to help these mice stay awake at night (normally, mice are asleep during the day and awake at night). Compared to the untreated mice, the R6/2 mice that had their sleep/wake cycles regulated by drugs showed improved performance in a series of cognitive tasks. The authors hypothesized that these beneficial effects could be due to restoration of the mice’s circadian rhythms, and that sleep therapy could one day be used to slow the progression of neurodegenerative diseases such as HD.  Another important benefit of sleep therapy could be for the caretakers of those with Huntington’s disease. Several studies have found that difficulty dealing with nocturnal sleep problems is one of the most common reasons that caretakers choose to institutionalize patients with neurodegenerative disease.

Although these mice studies are promising, the effects of sleep regulation on humans with HD have yet to be studied. However, the evidence so far indicates that sleep therapy might not only improve the symptoms of HD, but may even affect the progression of the disease. And the fact remains that we could all probably use some more sleep!

Sources^

Arnul, I. et al. (2008). Rapid eye movement sleep disturbances in Huntington disease. Archives of Neurology 65(4): 482-488.
This article presents the results of a study examining REM sleep problems in patients with HD. The introduction and comment section are quite informative and very readable.

Goodman, A. & Barker, R.A. (2010). How vital is sleep in Huntington’s disease? Journal of Neurology 257(6): 882-897.
This eminently-readable article provides an excellent review of the evidence relating disturbed sleep with Huntington’s disease.

Pallier, P. & Morton, J. (2009). Management of sleep/wake cycles improves cognitive function in a transgenic mouse model of Huntington’s disease. Brain Research 1279: 90-98.
This primary source presents the results of experiments assessing the effects of drug-induced sleep therapy on mice model of HD. The introduction and conclusion are quite interesting and generally quite understandable.

Rechtschaffen, A. (1998) Current perspectives on the function of sleep. Perspectives in Biology and Medicine 41(3): 359-391.
This article offers a comprehensive review on the function of sleep. Although the writing is slightly technical, it is still quite useful and comprehensible.

Reddy, A. & O’Neill, J. (2009). Healthy clocks, healthy body, healthy mind. Trends in Cell Biology 20(1): 36-44.
This review talks about the importance of circadian rhythms. The article is quite technical.

Siegal, J. (2005). Clues to the functions of mammalian sleep. Nature 437: 1264-1271.
This review article presents some of the current theories and analyzes some of the existing evidence regarding the importance of sleep in mammals. The writing is technical, but the main points are relatively accessible.

Zisapel, N. (2007). Sleep and sleep disturbances: biological basis and clinical implications. Cellular and Molecular Life Sciences 64: 1174-1186.
This very technical article gives a review of the many different problems associated with sleep disturbances.

Y.Lu 11/12/2010; recorded by B. Tatum 8/21/12

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Red Wine

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People have been consuming red wine for thousands of years. Although most people drink wine because of its pleasurable sensory effects, recent studies suggest that drinking red wine may confer several health benefits. Many researchers believe that these health benefits come from a compound in red wine called resveratrol, which has been shown to exhibit neuroprotective effects in several experimental studies in test tubes as well as in various organisms including yeast, worms, and mice. A few studies also provide insight into how resveratrol may affect mice with neurodegenerative disorders and more specifically mice with the mutant huntingtin protein.

Preliminary research has suggested that resveratrol may help protect against common HD complications such as inflammation, oxidative stress, and possibly huntingtin protein aggregation. (For more information on inflammation, click here.) Further studies of resveratrol in the context of neurodegeneration and Huntington’s disease (HD) are required to understand the role of resveratrol and to assess its efficacy as a therapeutic agent. This chapter gives an overview of our current understanding of how resveratrol may combat disease, as well as how these mechanisms may have potential for HD treatment.

Resveratrol in Red Wine^

Scientists became interested in exploring the health benefits of resveratrol when its presence was first reported in red wine, leading to the possibility that it could explain a health phenomenon known as the “French Paradox.” Despite the fact that the French diet is high in saturated fats, the rate of heart disease is lower than that observed in other industrialized countries. This paradox led to the idea that regular consumption of red wine (and thus a higher consumption of resveratrol) may provide additional protection from cardiovascular disease.  Recent studies have indicated that resveratrol is not the sole agent responsible for the cardioprotective effects associated with red wine consumption, and that other highly potent red wine constituents may have even greater effects.

Why not white wine or wine in general? The skins and seeds of grapes are used in the production of red wine, but not in the production of white wine. Because resveratrol is most highly concentrated in grape skins, the concentration of resveratrol is significantly higher in red wine than in white wine.

Resveratrol is one member of a class of compounds known as phytoalexins; “phyto” meaning “plant” and “alexin” meaning “to ward off or protect.” Phytoalexins are produced by some plants to respond to stressors such as injury, fungal infection, or ultraviolet radiation. Remarkably, resveratrol may be able to protect humans as well as plants.  Studies suggest that a high resveratrol intake is associated with reduced incidence of heart disease, cancer, and age-related diseases such as Alzheimer’s disease.  HD may also be a part of this list, but additional research is needed to test this notion.

Alcohol: The Fine Line Between Moderation and Excess^

Alcohol itself (better known in chemistry as ethanol) is toxic to the human body and has no redeeming qualities from a health perspective. After alcohol is consumed, a person’s blood alcohol level rises and the body begins to “detoxify” the alcohol. The first step in this process is the conversion of alcohol to another compound called acetaldehyde. Acetaldehyde stays in the body for several hours, producing a variety of undesirable toxic effects. Acetaldehyde binds readily to the walls of red blood cells. By attaching itself to the red blood cells, acetaldehyde reduces the oxygen supply to most of the cells of the body, including the brain. Acetaldehyde also combines with hemoglobin in the red blood cells and further reduces its ability to carry oxygen, which eventually leads to hypoxia (oxygen starvation at the cellular level).

Additionally, acetaldehyde interferes with the process of microtubule formation. Microtubules are essential to the brain because they provide structural support for nerve cells and their dendrites and they also transport chemicals manufactured in the nerve cells to the dendrites. Without microtubules, dendrites weaken and die. Deficiencies in various vitamins are also induced by acetaldehyde. Although individuals vary in vulnerability to acetaldehyde, it is clear that acetaldehyde is a dangerous and toxic chemical. In addition to the complications already mentioned, alcohol can also do significant damage to the liver and central nervous system. Thus, one must exercise caution when dealing with a powerful substance like alcohol and weighing its potential benefits and costs.

Roles of Resveratrol^

Antioxidant Capabilities^

Oxidative stress (also known as oxidative damage) is believed to play a major role in the damage of nerve cells in HD. (For more information on oxidative stress, click here.) Studies indicate that resveratrol is an excellent antioxidant, which means that it is very good at combating oxidative stress. What makes resveratrol such a good antioxidant? Researchers believe that it works by inhibiting monoamine oxidase (MAO), an enzyme primarily found in the liver and nervous system that generates free radicals. Free radicals are dangerous because they are highly reactive. They tend to react with important structures in cells and accelerate cell injury. By reducing levels of MAO, resveratrol decreases the number of free radicals that degrade nerve cells. Decreasing the level of free radicals may slow the progression of neurodegenerative diseases such as HD.

In scientific studies, injecting resveratrol into rats led to decreased levels of certain free radicals in the brain. Additionally, the activities of several antioxidant enzymes increased. Not only can resveratrol help to prevent free radicals from forming, but it can also decrease the toxicity of free radicals by inhibiting a process called lipid peroxidation. Lipid peroxidation is the process whereby free radicals take away electrons from the lipids that make up our cell membranes and thereby cause damage to the cell. (For more information on lipid peroxidation, click here.) Rat studies indicate that resveratrol significantly inhibits lipid peroxidation in cells.

While resveratrol has been shown to be a powerful antioxidant in vitro and in rats, its role as an antioxidant has yet to be tested and confirmed in humans.  Because circulating and intracellular levels of resveratrol in humans may be much lower than in vitro models, its true effects on the human body are controversial.

Anti-inflammatory Capabilities^

Long-term, or chronic inflammation in the brain is believed to play a significant role in neurodegeneration in HD. Studies indicate that resveratrol acts as an anti-inflammatory agent mainly by inhibiting the action of two key enzymes: cyclooxygenase and lipoxygenase. These enzymes lead to the production of leukotrienes and prostanoids, which are chemicals that significantly contribute to the inflammatory process. Resveratrol inhibits cyclooxygenase and lipoxygenase and their production of inflammatory substances, causing inflammation to decrease.

Resveratrol may also inhibit pro-inflammatory transcription factors, which increase inflammation. Transcription factors are proteins that bind to DNA and regulate gene expression by promoting transcription. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and activator protein-1 (AP-1) are examples of pro-inflammatory transcription factors.  NF-kB is a transcription factor for genes that helps cells to survive, bind to a surface, specialize and grow.  It is also involved in cell inflammation.  AP-1, or activator protein-1, is also a transcription factor involved in cell proliferation and survival. Research has shown that most anti-inflammatory agents suppress NF-kB activation.  Studies have indicated that resveratrol may inhibit NF-kB and AP-1 pathways, thus preventing inflammationResveratrol has been shown to decrease levels NF-kB directly and indirectly via inhibition of associated MAP kinases, which is discussed in the “MAP kinase” section of this article.

It is still unclear how resveratrol decreases inflammation. Some studies have shown that these anti-inflammatory effects may be partially due to resveratrol’s antioxidant capabilities, while others have shown that resveratrol’s anti-oxidant and anti-inflammatory capabilities are independent of one another. Further research is necessary to arrive at a scientific consensus.

Resveratrol has been shown to have neuroprotective effects in neurons, in rat brains and in cell culture. This suggests that the anti-inflammatory capabilities of resveratrol could potentially be beneficial in HD treatment. However, this hypothesis remains to be tested.

How Resveratrol Works^

Resveratrol has a very simple chemical structure, which enables it to play a role in a wide range of biological processes. As a result, resveratrol is able to act upon many different systems within the body. The following sections discuss some potential mechanisms through which resveratrol may exert its effects.   Please note that the mechanisms outlined in the sections “Heme oxygenase,” “MAP Kinase,” “Sirtuins,” and “Prevention of Neurodegeneration,” are interdependent and influence one another in ways that are not yet understood by the scientific community.

Heme oxygenase^

Similar to resveratrol, an enzyme called heme oxygenase (HO) also decreases oxidative stress and inflammation. Because of this similarity, researchers hypothesized that resveratrol might exert its function via a mechanism involving HO. This hypothesis was supported by a study that found that when resveratrol was administered to rats, the amount of HO in the rats’ neurons increased. The effect was dose-dependent, meaning that levels of HO increased as more resveratrol was administered. The connection between resveratrol and HO is important because HO is thought to have neuroprotective effects. In addition to being a powerful antioxidant, HO also produces several byproducts that may assist in cell survival.

HO is involved in regulating cellular uptake and storage of iron. Iron levels must be tightly regulated because adequate amounts of iron are essential for many cellular functions, but excessive amounts of iron can lead to the formation of reactive oxygen species (ROS). A ROS is a highly volatile compound, which is likely to damage cells. When resveratrol increases the amount of HO, higher levels of HO may in turn affect the level of iron in the cells. Thus, one way resveratrol may exert its neuroprotective effects is by stimulating HO to balance out iron levels and protect from iron-mediated toxicity.

Although the connection between resveratrol and HO is quite intriguing, further research is needed to determine the exact details of how they work together to protect nerve cells.

MAP kinase^

Numerous studies have demonstrated that resveratrol interacts with certain mitogen-activated protein (MAP) kinase family members. MAP kinases are proteins that respond to stimuli and regulate important cellular functions including gene expression cell survival and differentiation.

Earlier studies of MAP kinases indicated that resveratrol activated all three subfamilies of the enzymes, some of which have been linked to changes in brain cells changes that form the basis of memory and learning processes.  However, the relationship between resveratrol and memory and learning processes has not been tested since the preliminary studies were published.

More recent studies have investigated how the effects of resveratrol on MAP kinases influence the expression of inflammatory mediators NF-kB and AP-1. See the “Anti-inflammatory Capabilities” section in the article to learn more about NF-kB and AP-1. In short, resveratrol inhibits NF-kB and AP-1 by acting on MAP kinases. MAP kinases reduce inflammation in part by encouraging cell death.   Studies have also suggested that the inhibition of NF-kB combats beta-amyloid plaques in neurons, helping neurons survive. See the section on “Resveratrol and the Prevention of Neurodegeneration.”

The MAP kinase subfamilies are most likely related to a wide range of other processes, some of which are related HD.  It is possible that some MAP kinases regulate heme oxidase, helping to combat oxidative stress and reduce chronic oxidative damage. (See “Heme Oxidase”)

Modulation of MAP kinases by resveratrol may inhibit or activate various pathways which in turn could reduce inflammation, promote cell death when need be, and protect against buildup of toxic protein fragments.  However, such potential effects of resveratrol on MAP kinase related pathways and the potential relevance to HD still must be investigated.

Sirtuins^

Studies in yeast and fruit flies have demonstrated that resveratrol activates a group of enzymes called sirtuins, which promote longevity in a variety of organisms. Sirtuins are important for many cellular processes including gene silencing, regulation of the cell cycle, fatty acid metabolism, apoptosis and longevity. Research has also shown that resveratrol activates an enzyme called SIRT1, the human analog of the Sir2 protein, which is found in yeast. The function of SIRT1 in humans is similar to that of Sir2 in yeast; it mediates the cell cycle, protects the cell during stress, regulates transcription, prevents the destruction of axons, and is involved in extending the life span of cells. In mice, increased production of the SIRT1 gene shows both a protective and pro-aging role in neurons. Furthermore, researchers have demonstrated that both resveratrol and direct expression of the SIRT1 gene slow neurodegeneration and cognitive decline in mouse models of Alzheimer’s disease (AD).

The majority of research supports the hypothesis that resveratrol, by stimulating the activity of sirtuins, mimics the effects of calorie restriction. (For more information on dietary restriction, click here.)  Calorie restriction has extended the life span in rodents and primates through a variety of mechanisms, one of which includes increasing levels of SIRT1.  It has even been shown to slow disease progression and increase survival in huntingtin mutant mice.  Both calorie restriction and resveratrol can decrease chronic oxidative damage, inhibit inflammatory pathways, and increase energy production in the cell. While a few studies suggest that sirtuins act independently of pathways mediated by calorie restriction, these studies do not propose an alternative mechanism for sirtuin action. Regardless of the relationship between resveratrol and calorie restriction, activation of SIRT1 proteins has had positive effects on a variety of organisms including mouse models for HD and AD.  This suggests that resveratrol itself may have the potential to delay the onset and progression of HD symptoms.

Resveratrol and the Prevention of Neurodegeneration^

Resveratrol has demonstrated neuroprotective effects through its anti-oxidant and anti-inflammatory capabilities, as well as its influence on sirtuins. Expanding upon these claims, numerous epidemiological studies (studies related to epidemiology) have determined that moderate red wine consumption is correlated with a lower incidence of dementia and a reduction in Alzheimer’s disease. (For a comparison of Alzheimer’s and HD, click here.) Nevertheless, it should be noted that the notion that red wine intake lowers AD risk is controversial. Based upon controlled studies, a dose of resveratrol much higher than the amount in red wine is needed for any positive effects. The correlation between reduced risk of dementia and moderate red wine consumption does not mean that red wine consumption or resveratrol are responsible for the reduced risk. Studies are ongoing to prove if correlation will translate to causation in this case.

Evidence suggests the possibility that resveratrol can prevent neurodegeneration in AD via protection against beta-amyloid plaquesBeta-amyloid (Aβ) plaques are an accumulation of small fibers called beta-amyloid fibrils and are present in the brains of people suffering from Alzheimer’s disease (AD). (For more on beta-amyloid plaques, click here.) These plaques are thought to greatly contribute to the neurodegenerative process of AD.  Over the past decade, there has been compelling evidence that resveratrol has the ability to protect against the neurotoxic effects of amyloid-related proteins.

In one study, researchers treated mice injected with the AD gene with resveratrol, which reduced the number of Aβ plaques.  Another study found that moderate consumption of red wine lowered Aβ levels and reduced its neurotoxic effect, implying that red wine intake may have a beneficial effect against AD pathology by promoting mechanisms that work against the accumulation of beta-amyloid plaques. Additional studies in mice and in cell cultures have supported these findings.

Because of the parallels between huntingtin protein aggregates and beta-amyloid fibrils, these results are promising developments in the search for treatments for neurodegenerative disorders like HD.  It is possible that resveratrol may also have the ability to decrease huntingtin protein aggregates. However, this hypothesis remains to be tested and other substances that have decreased beta-amyloid fibrils have had no effect on huntingtin protein aggregates.

Future studies aimed at elucidating a more detailed understanding of the various cellular mechanisms involved in the neuroprotective effects of resveratrol have the potential to open new avenues for the treatment of neurodegenerative diseases such as HD.  It is necessary to further study resveratrol in animals and most importantly, humans, before it can be proven as a safe, effective treatment for HD.

Therapeutic Potential of Resveratrol^

There are two measures that are used to determine the effectiveness of a drug: pharmacokinetics, how the body processes a drug, and bioavailability, the degree to which a drug or other substance becomes available to the target tissue after administration. Both the pharmacokinetics and bioavailability of resveratrol are still inconclusive.  Studies in mice, rats and dogs have consistently shown that resveratrol can be absorbed and distributed in the blood stream at relatively high concentrations. However, due to its rapid metabolism and elimination from the human body, the potential impact of resveratrol on humans is debatable. There are a few major problems with resveratrol:

First, humans who receive an oral dose have plasma concentrations of resveratrol that peak after only 30 or 60 minutes.  This shows that resveratrol is indeed metabolized quickly and may not be able to exert its positive effects before being metabolized.

Second, the dose of resveratrol needed to experience positive health effects remains unclear. Sirtris Pharmaceuticals Inc. is using very high doses in phase II clinical trials (2500 mg and 5000 mg per day) of this drug for diabetes. However, other scientists believe resveratrol supplements should be taken in lower doses. No other human clinical trials or studies have been conducted in order to determine the amount of resveratrol needed to exert its positive effects. The amount of resveratrol in a bottle of red wine can vary between types of grapes and growing seasons, and can vary between 0.2 and 5.8 milligrams per liter. While some research suggests that drinking a moderate amount of red wine (1 to 3 glasses a day) may provide enough of the active compound to exert protective effects, controlled scientific studies have not been undertaken to verify this hypothesis. Although resveratrol can be concentrated and obtained in capsule form, taking these supplements may not have the same effect as drinking red wine, primarily due to the reason explained below.

Third, resveratrol degrades quickly when it is exposed to oxygen. For example, resveratrol is no longer active in wine if the bottle has been opened for 24 hours. This directly applies to the manufacturing of resveratrol supplements, which are most likely exposed to air during the manufacturing process or storage. This presents an obstacle to supplement preparation and necessitates careful handling of the substance. It is very likely that the majority of marketed preparations of resveratrol do not contain the active form that is found in red wine.

While a few phase I clinical trials have shown that resveratrol is safe in certain doses for healthy participants and people with type II diabetes, many more clinical trials on humans are necessary before conclusions can be made regarding the effects of resveratrol in the context of neurodegenerative diseases such as Huntington’s disease.

Conclusion^

Resveratrol has been shown to have wide-ranging positive effects on many diseases. Research has revealed resveratrol’s ability to protect against some of the common HD complications by decreasing inflammation, combating oxidative stress, increasing the energy production in cells, and potentially reducing huntingtin protein aggregates. However, it is important to note that nearly all of the research on resveratrol has been done in cell culture and in mice, and this data may not necessarily apply to humans. As more studies are conducted regarding the mechanism of resveratrol, the amount necessary in human body in order to have protective effects, and the effects of resveratrol supplements in humans, we will have a better idea about how resveratrol works and whether it will be an effective treatment for patients with neurodegenerative diseases such as HD.

For further reading^

-D. McGee, 01/11/05, and P. Bakhai, 6/19/10

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Physical Exercise

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Physical-Exercise

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

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

Exercise and Capillary Density^

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

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

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

Exercise and Cognitive Maintenance^

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

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

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

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

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

BDNF^

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

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

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

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

Exercise and Stress Alleviation^

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

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

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

Biological evolution of exercise^

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

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

Exercise and HD^

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

Getting Started^

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

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

For further reading^

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

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

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Physical Therapy and Huntington's Disease Treatment and Management

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The onset of Huntington’s disease (HD) is heralded by a wide range of symptoms, from behavioral ones, such as depression and irritability, to physically visible ones, such as bodily tremors, bradykinesia, akinesia, and dysphagia. As the disease advances, symptoms become progressively severe. Physical symptoms, such as involuntary movements, worsen, potentially leading to frequent falls. Although there is currently no cure for HD, there are many treatment regimens that may help slow the progression of symptoms. While most research is aimed at developing drugs and medications to help alleviate HD symptoms, physical therapy interventions also have the potential to improve the quality of life for many patients.

There are three main types of physical therapy: physio-, occupational, and speech. Although there is overlap between these treatments, each type of therapy differs slightly in its goals and how it works.

Types of Physical Therapy^

Physiotherapy is physical therapy that focuses primarily on the control of larger bodily motions, such as walking and standing. Occupational rehabilitation aims for ‘adaptive’ improvement—learning new ways to accomplish day-to-day tasks involving fine motor skills made difficult by HD symptoms. Speech therapy deals with the patient’s physical difficulties involving mouth and throat muscles, and the process of speaking. Below is a table summarizing some of the major components that each type of therapy addresses:

Physiotherapy Occupational Therapy Speech Therapy
  • Gait and balance
  • Fall prevention
  • Aerobic capacity
  • Muscle strength
  • Wheelchair prescription and training
  • Respiratory function
  • Task-specific reach, grasp, and manipulation
  • Personal hygiene
  • Grooming and dressing
  • Eating and drinking
  • Toileting
  • Work restructuring
  • Driving assessment
  • Memory training
  • Provision of adaptive devices
  • Speech intelligibility- control of rate and volume
  • Intonation
  • Speech rhythm
  • Swallowing
  • Eating
  • Respiration
  • Language comprehension

Physiotherapy involves several large areas of rehabilitation. It may focus on gait, balance transfers, general strengthening, coordination, and postural stability. Many different types of exercises are performed in this type of treatment, as each patient’s individual exercise regime will vary depending on his or her specific needs. The different exercises focus on training different areas of the body, but all aim to prevent falls, promote correct walking and body control, build coordination, and encourage a positive and confident attitude towards the body. Exercises are done in a variety of positions—lying down, sitting, and standing. Some exercises make use of common gym props and machines such as exercise bicycles, treadmills, weighted balls, and dumbbells, while others focus on flexibility or posture training. In posture training, exercises help patients maintain good form and balance while moving and staying still. For example, a patient may be asked to focus on transferring body weight from one leg to the other or to walk with hands clasped behind the back.

Like physiotherapy, occupational therapy is individually tailored. This type of rehabilitation integrates both mental and physical exercises to aid patients in learning new strategies to accomplish tasks that become more challenging as HD progresses. Activities focus on memory stimulation and concentration as patients learn approaches for completing common tasks such as walking or standing safely, dressing, and personal hygiene. Oftentimes, an occupational therapist will also aid in assessing whether or not it is practical and safe for a patient with HD to continue driving, and also in recommending changes in the work environment to better accommodate the progressive symptoms of HD.

Speech therapy attempts to help patients regain or maintain verbal adeptness, and other skills related to the mouth and throat. Respiratory exercises such as blowing up balls and blowing on tissues at different distances aim to increase the efficiency of breathing. On the cognitive side of speech rehabilitation, patients complete exercises which test and strengthen their ability to understand, interpret, and use metaphors, synonyms and other figures of speech.

Effectiveness of Physical Therapy^

One study tracked 40 patients with HD over two years as they followed a comprehensive rehabilitation program. The regime included both the physical and cognitive aspects from physiotherapy, occupational therapy, and speech therapy. The findings showed that over time, physical therapy had positive effects on motor and functional performance. Moreover, cognitive abilities did not decline as would be otherwise expected. These results indicate that patients are able to, at the very least, maintain a constant level of functional, motor, and cognitive performance over two years with the help of physical therapy This is important because HD is characterized by a deterioration of these abilities. However, the problem with this type of study is the lack of control groups, and difficulty in quantifying progress in the absence of any common standards.

Despite the evidence indicating that physical therapy can help people with HD maintain independence and functional capacity, recent research suggests that it is not always routinely provided. One survey revealed that only 24% of patients with HD had worked with an occupational therapist, only 8% had been seen by a physiotherapist, and close to none had been contacted by a speech therapist. Although it is unknown why physical rehabilitation services are so rarely used by patients, several explanations have been proposed. One reason may be the fact that there are very few studies that quantify the effectiveness of such treatments. Another possible reason for the limited use of rehabilitation services is reluctance in the community of service providers to accept people who are afflicted with a progressive condition, because it is thought that their chances of improvement are exceedingly low.

If more rigorous studies are completed that definitely demonstrate the effectiveness of physical therapies in slowing disease progression and improving patient quality of life, perhaps these types of treatments will be recommended to HD patients in the future.

Further reading:^

  • Bilney, B., M. Morris, and A. Perry (2003). “Effectiveness of Physiotherapy, Occupational Therapy, and Speech Pathology for People with Huntington’s Disease: A Systematic Review.” Neurorehabilitation and Neural Repair 17:12-24.
    Less technical review which outlines many of the current treatments. Provided inspiration for the table in the “Types of Physical Therapy” section.
  • Busse, M.E, and A.E. Rosser (2007). “Can directed activity improve mobility in Huntington’s disease?” Brain Research Bulletin 72:172-174.
    Short, less technical review which summarizes some of the research that has been done in the field so far.
  • Zinzi, P., D. Salmaso, R. De Grandis, G. Graziani, S. Maceroni, A. Bentivoglio, P. Zappata, M. Frontali, and G. Jacopini (2007). “Effects of an intensive rehabilitation programme on patients with Huntington’s disease: a pilot study.” Clinical Rehabilitation 21:603-613.
    A technical paper which outlines a study on how rehabilitation affected patients over a longer time span. Data mentioned in the “Effectiveness of Physical Therapy” section was drawn from this study.

- A. Pipathsouk, 4/12/2009
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Talking to Children About Huntington's Disease

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Families choose to discuss Huntington’s disease with children in different ways according to their personal beliefs about how best to handle this information. This article does not intend to imply that there is one right way to speak with children about this very difficult subject. The following information is based on the experiences of social workers and the families with HD with whom they have worked. Hopefully it can provide a starting point for communication, and can be adapted to individual families and circumstances.

Introduction^

Talking about HD is difficult because it is a complex diagnosis and it can have a profound and devastating impact on family dynamics. Parents often believe that HD is too complicated for an infant to understand, and too distressing for school age and adolescent children. In addition, the already challenging task of telling a child about his or her parent’s chronic illness is amplified in the case of HD, because the child is at risk of inheriting the disease. Caregivers fear that their child will someday develop symptoms of HD and want desperately to provide him or her with a normal childhood, free from the anxiety, sadness, and anger that living with HD entails. Moreover, some parents worry that by telling their child about HD, they will subject him or her to genetic discrimination, which could limit social relationships and opportunities. Despite all of these concerns, most families and social workers agree that establishing open and honest communication about HD from a young age, rather than avoiding this topic altogether, is less damaging and more beneficial for all members of the family.

While keeping quiet about HD in the family seems like a way to protect a child, it often does more harm than good. Even when the condition is not discussed, small children commonly pick up on the notion that parents are anxious and worried, and that something is wrong with the parent with HD. If the diagnosis is not at least explained in simple terms to the child, he or she might feel responsible for causing the strange behavior of the affected parent. In addition, a common symptom of HD is irritability. If a parent’s irritable behavior is not explained properly, a child may not understand that the parent’s anger is not directed at him. Inability to discuss HD can also eventually lead to poor preparation for future changes in the family as the symptoms of the parent with HD grow more severe.

Talking to a child about HD helps the child understand why his mom or dad is acting strangely and can make it easier for the whole family to cope with the diagnosis. Open communication creates a safe environment to discuss and ask questions about a very distressing illness, and it reduces individual feelings of isolation for the child as well as the stress of secrecy for the parents.

When do I tell my child about HD?^

Most social workers who work closely with families with HD believe that children should be told at any and every age. It is never too early and never too late to discuss HD with a child. Children are surprisingly resilient and often have a greater than expected capacity to cope with such disturbing news. Children who sense already that something is wrong with a parent may actually feel relieved to hear facts about HD because these are sometimes more hopeful than their fears. The information given to children about HD will clearly be more basic for those who are younger, but evidence based on adoptive studies indicates that the younger the child is when told about the diagnosis in the family, the easier it will be to cope in the long run. This is because the child will begin to integrate this information as part of his life so early that it will seem more normal and therefore less scary. It is helpful to know that the talk itself is often less stressful than the anticipation leading up to it.

How do I tell my child about HD?^

When first discussing HD with a child, it is important to tailor the discussion appropriately to age level. If there is more than one child in the family, it may be important to speak to each of them separately, giving more details to those who are older. However, it is a good idea to begin the basic discussion with the entire family present to establish trust and make sure that nobody feels left out. While the first conversation about HD is often the most stressful for the parent, it is important to keep in mind that it is the first discussion of many. The topic will need to be revisited periodically to make sure that children have the most updated information, to give them the opportunity to ask questions, and to make sure they are coping in a healthy way.

When talking about HD, it is necessary to keep in mind the developmental level of the child and to gauge how much to say about HD by disclosing information gradually. HD is a complicated illness and abstract thinking does not develop until adolescence. Before then, complex discussions about this condition will only confuse the child.

When having this discussion, parents need to offer children reassurance and leave them with a sense of hope. In addition to worrying a lot about the parent with HD, children will often be concerned about what will happen when the parent’s symptoms get worse. It is important to assure children that no matter what, there will always be someone to care for them. It is also important to leave children with a sense of hope. Parents need to emphasize that doctors and researchers are working hard every day to improve therapies and to find a cure for HD.

Don’ts^

There are some things to remember not to do when discussing HD with children. First and foremost, the parent should never lie. Lying takes a lot of energy and it can become complicated to lie about certain pieces of information for extended periods of time. A lie is difficult to remember and ever-changing explanations lead to disbelief and mistrust. Honesty fosters trust and a sense of security, both of which can enable open discussion and make coping with HD as a family much more manageable.

The scientific and medical information related to HD is complicated and will be too difficult for small children to understand. Therefore, when talking to young children, the parent must be conscious not to overburden them with too much medical information after explaining the diagnosis in basic terms. If the parent is trying to answer a child’s question, it is a good idea for him or her to ask if the child understands or has additional questions. If the child wants more information, then the parent should elaborate.

It is important for the parent not to make promises that cannot be kept, thus giving the child a sense of false hope that may someday be devastating to the child. For example, if the child has not been tested for HD, the parent cannot promise that the child will never develop symptoms of this disease. The parent should inform the child that such a test is possible and could be considered after age 18.

Parents should not be afraid to say that they don’t know the answer to a question. Not knowing may mean that the individual parent doesn’t have the answer to a question but can find somebody who does. It may also mean that nobody knows the answer to the question and this is also perfectly okay. For example, no one knows exactly when there will be a cure for HD. We all hope that it is soon, but no one knows at least for now and the child is not alone in waiting for an answer.

Talking about HD with specific age groups^

As mentioned previously, the information parents give to a child about HD should be appropriate to the child’s age. There will likely be individual differences in suitable information depending on the child’s maturity level, but the following provides a general frame of reference for age-appropriate discussion.

When talking to preschoolers, children ages 2-5, parents should use language that their children understand and keep their explanations short. Children this age may begin to show signs of anxiety, so it is often helpful for parents to let them know the ways in which they are keeping their daily routines the same, in spite of having HD in the family. Routine can be very soothing, even for small children, and so emphasizing this creates comfort that their lives aren’t changing too much all at once. This gives the children space to integrate the new information they receive on HD and therefore to cope. For children in the older portion of this age range, it should be made clear that nothing they did caused HD. This is important because children around this age are prone to magical thinking, believing that they have the ability to make certain things happen, simply by wishing for either good or bad things. If a child does not understand why the parent has HD, the child may attribute the symptoms to his or her wish, resulting in a profound sense of guilt.

School age children, children ages 6-11, are generally capable of understanding a basic explanation of the disease. It often helps to give the child the name of the disease and to point out that you cannot catch it by hugging or sharing food with the individual who has it. It is also a good idea to give the child an overview of what doctors are doing to control the symptoms of HD even though there is, as of yet, no cure. It is important for parents to realize that children in this age range can become overly concerned with health and that it is possible that if they are given too much information, they may worry about HD well before the onset of specific symptoms.

Teenagers are generally very capable of understanding a lot about HD. Because of this, parents should be open and willing to give as much detailed information as the teen needs to understand the illness. Most agree that at this point, parents should answer all questions, including ones about transmission, as fully and as honestly as possible. However, this stage of life is often difficult because of the many physical and psychological changes that emerge as part of adolescence. This is a time when individuals formulate and strengthen their self-identities and establish important peer and other relationships. Often teens are prone to mood swings, anxiety and depression and may become angry or withdrawn when HD is discussed. If this is the case, it is important for the parent not to force the teen to talk about HD, but to make himself or herself available when and if the adolescent should decide to talk about the condition. At this point, it is also helpful to have an open discussion about stigma associated with HD and how people are often afraid of behavior that seems different or that they don’t understand.

In conclusion^

Deciding when and how to talk to children about HD may involve significant mental preparation. The above can be considered as a starting place for parents who want ideas as to where to begin. One helpful idea is for the parent with HD to think about how HD was discussed when he or she was growing up and to consider whether or not it was an effective way to deal with the diagnosis and what, if anything, he or she might have changed. Drawing from personal experience might make it easier for the parent to communicate information about HD.

Social Workers Bonnie Hennig, author of Talking with Kids About HD, and Rick Henry of the HDSA Center of Excellence at University of California Davis Medical Center, were instrumental in the writing of this article. They are helpful contact persons for more detailed and personalized guidance.

Recommended Resources and Links for Children^

For Further Reading:^

  • Hennig, Bonnie. Talking to Kids About HD. 2004.
    This book provides information about how to discuss HD with children at different developmental stages. It is the basis for much of the information in this article.
  • Keenen, K. et al. “Young people’s experiences of growing up in a family affected by Huntington’s disease.” Clinical Genetics 71 (2007): 120-129.
    This article examines the experiences of young people in families affected by HD. It cites knowing about HD from an early age in particular as a factor in coping effectively with the illness in the family.
  • Lefebvre, A. “Talking to children about HD in the family.” Horizon Newsletter. Winter, 1999. Online here.
    This article discusses some ways of approaching HD with different age groups. It is short and easy to read.
  • Lowit, A. and van Teijlingen, E.R. “Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington’s Disease patients.” BMC Family Practice 6 (2005). Online here.
    This study involved interviews of ten carers of spouses with HD. Although the number of participants is small, the article discusses interesting insights into the psychosocial impact of not discussing HD within the family.

– A. Frohnmayer, 5/22/09

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Meditation and HD

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The practice of meditation is often viewed by Westerners as merely a form of relaxation. Many people assume that the benefits of meditation are limited to stress relief and decreased blood pressure. Brain research, however, is beginning to produce concrete evidence for something that Buddhist practitioners of meditation have believed for centuries: that mental discipline and meditative practice can physically change brain functioning and preserve and enhance numerous cognitive functions. Because it is often associated with transformed states, meditation has traditionally been understood in transcendent terms – as something outside the world of physical measurement and objective evaluation. But over the past few years, through the use of advanced new technologies, scientists have been able to come up with biological explanations for meditative phenomena. The results of several innovative studies reveal that the human brain has the ability to adapt and change in ways that were previously unimaginable. For a person with a neurodegenerative disease such as HD, these results suggest that it may be possible, by engaging in some sort of meditative practice or mental discipline, to maintain motor control and cognition and possibly delay the onset of many neurological symptoms. The following chapter examines the practice of meditation and its effects on the circuitry of the brain, as well as how this practice may potentially benefit someone with HD.

The Dalai Lama, Meditation, and Neurobiology^

The Dalai Lama, the head of state and spiritual leader of the Tibetan people (who practice Tibetan Buddhism), has played a pivotal role in opening the lines of communication between Western scientists and Buddhist scholars. Frequently, he calls leading psychologists and neurobiologists together to discuss the latest scientific thinking in fields related to the human mind. When he accepted the Nobel Peace Prize in 1989, he commented, “Both science and the teachings of the Buddha tell us of the fundamental unity of all things.” In fact, Tibetans in general seem to share this enthusiasm for science. Tibetans were surprisingly the most proportionately represented ethnic group working on the Human Genome Project. (For more information on the Human Genome Project, click here.) Even though they account for only 0.1% of the world’s population, they made up about 10% of the project’s workforce.

In particular, Tibetan Buddhist monks are interested in science because they have an intense curiosity about the workings of the brain. Monks typically spend hours in meditation each day, and claim that this practice enhances their concentration, memory, and learning ability. They believe that the brain is capable of being trained and physically modified in remarkable ways. Scientists used to believe the opposite – that connections among brain nerve cells were fixed early in life and that adult brains were more-or-less complete and unchangeable. When nerve cells died, it was believed that they were simply gone forever and could never be replaced. But that assumption has fortunately been disproved over the past decade with the help of advances in techniques such as brain imaging. In its place, scientists have embraced the concept of neuroplasticity, which refers to the brain’s ability to change its structure and function by expanding or strengthening connections between nerve cells that are frequently used and by shrinking or weakening those that are rarely engaged. It turns out that new nerve cells do grow and our brains are much more flexible than was once believed. A key component of Buddhist belief is that meditation literally transforms the mind. Thus, Buddhists are highly interested in scientific advances that could possibly help explain and/or provide evidence for this phenomenon. The question as to whether meditative phenomena have a biological basis is intriguing not only to the Dalai Lama and other Buddhists, but also to many neuroscientists. The collaborations between Western scholars and Buddhist monks are invaluable because the study of trained meditators can provide insights into the mechanisms behind important brain functions, as well as into possible therapeutic approaches related to lifestyle.

Neuroscientists and Buddhist monks: Results of an unusual collaboration^

The Dalai Lama, very much aware of neuroplasticity’s potential to interact meaningfully with Buddhism, encouraged monks to lend their brains to science so the workings of their meditating minds could be explored scientifically. Ultimately, he dispatched eight of his most accomplished practitioners to a neuroscience laboratory to have them hooked up for electroencephalograph (EEG) testing and brain scanning. The tools with which cognitive neuroscientists measure brain activity have grown very sensitive, allowing scientists to observe differences in brain activity between individuals doing the same task or even between different trials with the same individual. The Buddhist practitioners in the experiment had undergone training in meditation for an estimated 10,000 to 50,000 hours, over time periods of 15 to 40 years. As a control, 10 student volunteers with no previous meditation experience were also tested after one week of training.

Electrical activity and brainwaves^

Davidson et al (2004). The monks and volunteers were fitted with a net of 256 electrical sensors and asked to meditate for short periods. Thinking and other mental activity are known to produce slight, but detectable, bursts of electrical activity as large groupings of nerve cells send messages to each other, and that is what the sensors picked up. Richard Davidson, head of the experimental neuroscience laboratory, was especially interested in measuring gamma waves, some of the highest-frequency and most important electrical brain waves.

It is well known that the brain has electrochemical properites. A fully functioning brain can generate as much as 10 watts of electrical power. Even though this electrical power is very limited, it does occur in very specific ways that are characteristic of the human brain. Electrical activity emanating from the brain is displayed in the form of brain waves. Brain waves, or the “EEG,” are electrical signals that can be recorded from the brain, either directly or through the scalp. These brainwaves are organized into categories, ranging from the most active to the least active in terms of frequency.

The frequency of the brainwave, measured in cycles per second, is associated with its speed. Different frequencies indicate different levels and types of activities. Delta waves have a very low frequency (below 4 hertz) and occur during sleep. Alpha waves, 8 to 13 hertz, occur at relaxed, quiet times. Beta waves, 15 to 40 hertz, are the next fastest, occurring when we are actively thinking. Gamma waves (greater than 40 hertz) have the highest frequency and are involved in higher mental acuity, including perception and consciousness. They are thought to play an essential role in nerve cell communication.

The brain contains hundreds of billions of nerve cells. Researchers believe our thoughts are created when large groupings of these nerve cells “fire,” or send messages to each other, through bursts of electrical activity at the same frequency. Many scientists believe that synchronized neural firing, which occurs when masses of nerve cells fire or emit electrical signals at the same frequency at the same time, lies at the root of numerous essential cognitive functions, including memory and perception. Gamma wave activity, in particular, exerts a powerful influence on the brain because the production of gamma waves involves thousands of nerve cells moving at extremely high speeds in unison. Interestingly enough, Davidson found that the gamma waves in the monks showed much greater activation, and the movement of the waves was far better organized and coordinated than in the non-meditating students. The meditation novices showed only a slight increase in gamma wave activity while meditating, while some of the monks produced gamma wave activity more powerful and of higher amplitude than any previously reported in a healthy person in the neuroscience literature.

In addition to frequency, brain waves can also be measured in terms of amplitude, which describes the size of the wave. It is thought that brain wave amplitude is related to the amount of nerve cells present, as well as the degree of synchronization, with which the nerve cells fire. In other words, when an individual has a lot of nerve cells that fire well together, the size of the brain waves will be larger than when there are fewer nerve cells or when the nerve cells are not firing well together. The fact that the monks showed such high amplitude gamma wave activity is significant because it indicates that not only do they have a lot of healthy nerve cells, but these same nerve cells are also firing with a high degree of synchronization. Synchronizations of neural firing at high frequencies (gamma waves) are thought to play a crucial role in integrating scattered neural processes into a highly ordered cognitive act such as memory and in inducing synaptic changes. In other words, when nerve cells are firing with a high level of synchronicity (as they were in the monks’ brains), brain cells are able to communicate with each other much more readily and the entire brain is able to function more efficiently. It is important to note, however, that the potential benefits of increased gamma wave activity are based upon inferences that have yet to be proven. More research needs to be done.

Gray Matter^

Davidson has done follow-up studies and has concluded that meditation (along with increased gamma wave activity) results in a redistribution of gray matter in the brain, as well as a decline in the loss of gray matter. The decline of gray matter, which is natural but accelerated in HD, mirrors a decline in cognitive function and processing ability. The brain has two main layers: gray matter and white matter. The layer of gray tissue surrounds a whitish core, like the peel of an orange around its juicy interior. Gray matter is the command and control center of the brain where all the nerve centers are located. White matter, composed mainly of transmission facilitating sheaths known as myelin, simply connects the gray matter together. In the gray matter, we have motor-controlling cells and damage to these cells results in stroke. Stroke can paralyze any muscle that you can voluntarily move, including those of speech. It has been found that individuals with HD typically have a substantially reduced volume of gray matter in the brain, especially in the temporal lobe and the frontal lobe.

In fact, the decline in gray matter is so closely tied to the progression of HD that it may serve as a marker for the degree of brain atrophy. In other words, by measuring the amount of gray matter loss, researchers may be able to predict not only how much the HD has progressed, but also how much the brain has atrophied. This connection is likely due to the fact that an important brain structure known as the caudate nucleus is situated deep in the gray matter. The caudate nucleus is a nerve center that is essential for controlling movement and cognitive processing and has been investigated heavily by HD researchers. When the gray matter volume is reduced, this structure becomes less able to carry out its functions. Because it connects to many different parts of the brain, this inability to function can have widespread effects. Deterioration of the caudate nucleus and its connections to other parts of the brain results in behavioral changes and the inability to control emotions, impulses, thoughts, and movements. When it becomes damaged, the individual may be unable to experience intense feelings of guilt, shame, or embarrassment and be unaware of mistakes that are evident to others. This inability may result in a lack of self-awareness and an inability to evaluate one’s own behavior, in addition to making social and personal relationships more difficult. HD researchers have also found that damage to the caudate nucleus makes it difficult for people with HD to prioritize tasks and organize their day, as well as to handle many simultaneous stimuli. Additionally, the caudate nucleus controls voluntary movement. (For more information on the caudate nucleus, click here).

As you can now see, the caudate nucleus is an extremely important structure in the brain and its deterioration (as a result of gray matter loss) directly leads to many common HD symptoms. It follows that any type of activity or treatment that is able to delay or prevent a loss of gray matter would also delay or prevent many common HD symptoms. Aging invariably leads to some gray matter loss, but this process is significantly accelerated in people with HD. Hence, it would be highly beneficial for a person with HD to incorporate activities into his/her life that may be able to prevent such a rapid loss of gray matter. Again, it is important to note that meditation has not been proven to preserve gray matter and this claim is based largely on the findings of a single researcher. Yi Rao, a neuroscientist at Northwestern University, says that the science of meditation is “a subject with hyperbolic claims, limited research, and compromised scientific rigour.” Rao further goes on to say that, “Davidson is a respectable scientist, but he has put his respectability on the line with this.” Davidson defends his work as the first step in a new field. “Meditation research is in its infancy.” There needs to be a lot more peer-reviewed research findings in order for Davidson’s claims to be substantiated.

Meditation and everyday life^

After reading about meditations’ potentially significant influence on the brain, many readers are probably at least a little bit curious about how to implement meditation into their own lives. As a word of caution, the possibility that there was a pre-existing difference in brain function between the monks and the novices in the study can’t be ruled out. In other words, there may have been a confound in the study because individuals who have high levels of gamma wave activity to begin with may be more likely to become monks. However, the researchers are fairly confident that this is not the case because the monks who had spent the most years meditating had the highest level of gamma wave activity. This “dose response” – where higher levels of a drug or activity have greater effect than lower levels – is what researchers look for to assess cause and effect. Thus, the researchers are also confident that anyone who begins to meditate will be able to experience its benefits. Unfortunately, practicing meditation can be incredibly daunting for novices because they think they have to achieve some form of transcendent state. The monks, however, insist that their state of mind isn’t dependent on any superhuman leaps into higher consciousness. It’s much more pragmatic than that: it’s as simple as training the mind to think differently.

The monks describe meditation as simply a form of mental exercise. Pichitr Thitavanno, a prominent Buddhist, explains, “Despite the importance of the mind, most people appear to take care of the body far more than the mind, often neglecting its exercise or training. They have three meals a day, take a bath twice, provide the body with clothes for the purpose of adornment in a variety of ways, and give it regular and well planned exercise in the form of sports and walking. Even in the case of medicine, the body as a rule receives priority in care and attention, with the mind all this time being neglected and regarded as almost nonexistent. The mind is left uncared for until it becomes dusty, dirty, and polluted because of lack of exercise, training, and development.” In light of this fact, Buddhism introduces the ways and means of strengthening and exercising the mind. Buddhists believe that a mind well-trained and strengthened in the proper manner will help bring peace and progress both to the individual and to society as a whole. It is important to note that Buddhists do not believe that one must become a Buddhist in order to experience the benefits of meditation. Similarly, Davidson believes that the monks’ brains differed so dramatically from the novices not because they are Buddhists who practice meditation, but because they frequently engage their minds in mental training. In other words, meditation serves as a form of mental exercise that strengthens the brain, in much the same way that running or working out serves as a form of physical exercise to strengthen the body.

It is very important to note that meditation isn’t just performed by Buddhists. Nor is there only one form of Buddhist meditation. Nor does one have to believe in the other precepts of Buddhism to benefit from some of the Buddhist methods of meditation. There are secular meditation courses as well as religious.

Just as physical exercise can seem daunting to a person who has never worked out before, mental exercise such as meditation can seem daunting because it is unfamiliar and may feel unnatural. The key is to start off slow and come up with a routine that suits you. It is also important to realize that there is no right way to meditate; there are many different traditions of meditation and many different ways to meditate. In Davidson’s study, he had the novices practice mindfulness-based meditation, which is a state of alertness in which the mind does not get caught up in thoughts or sensations, but lets them come and go, much like watching a river flow by. This type of meditation is a good way for beginners to start. To begin, sit quietly for 10 to 20 minutes while concentrating on a single object or on the flow of your breath. When your mind begins to wander, note the new thought or sensation and then gently bring your concentration back to your original focus.

Another major form of meditation known as Vipassana, which means to see things as they really are, is one of India’s most ancient techniques of meditation. It was taught in India more than 2,500 years ago as a universal remedy for universal ills. The practice, which was taught by the Buddha, is non-sectarian and has universal application. It does not require conversion to Buddhism. While the meditation practices themselves vary from school to school, the underlying principle is the investigation of phenomena as they manifest in the five aggregates: matter or form, sensation or feelings, perception, mental formations, and consciousness. This process leads to direct experiential perception.

Another major form of meditation is that of Shambhala. Shambhala training is a nonsectarian path of spiritual training that emphasizes the cultivation of fearless, gentle, and intelligent action in the world. This action arises out of trust in innate human goodness and the inherent power and sacredness of the world, connecting with both through meditation practice as well as mindful activity in everyday life. Shambhala training welcomes people of all religious traditions as well as those who follow no particular spiritual path.

The practice of Japa meditation is the technique of using mantras (sounds) to open the heart and mind. The repetition of the sound is supposed to calm the senses and the mind and affect the chemistry of the body. One does not need to be religious to experience the benefits of Japa meditation. Mantras (sounds) can be whatever one chooses – they do not need to be religious mantras. For example, during an inhalation, one might say “I am” and during an exhalation one might say “at peace.” This practice allows the mind to focus and concentrate, and clear away other thoughts, emotions, and distractions which normally divert energies.

Conclusion^

The unusual collaboration between psychiatrist Richard Davidson and several Buddhist monks unveils the possibility that the brain, like the rest of the body, can be altered intentionally. Davidson and his colleagues put forth the idea that the phenomena of meditation can be translated into high-frequency gamma waves and brain synchronization, or coordination. Additionally, he found that meditation results in a redistribution of gray matter in the brain, as well as a decline in the loss of gray matter. These data suggest that meditation may induce short-term and long-term neural changes. These neural changes allow nerve cells to communicate and operate more effectively, thereby protecting and prolonging the vitality of the brain and several important brain functions. This finding is hopeful and encouraging for people with HD because it shows that there are things that can be done to actively combat the disease. Just as physical exercise sculpts the body and increases physical health, mental exercise sculpts the brain and increases mental health. With sufficient mental exercise and training, it is possible that the onset and progression of several common HD symptoms can be delayed. Meditation simply serves as a form of mental exercise; the key is to frequently train the mind. In the future Davidson hopes “to better understand the potential importance of this kind of mental training and increase the likelihood that it will be taken seriously.”

For Further Reading

  1. Cyranoski, David. Neuroscientists see red over Dali Lama. Nature 2005; 436: 452.
  2. Ellerman, Derek. “Buddhism and the Brain.” http://www.ellerman.org/BuddhismandtheBrain.htm.
    This highly technical article is an examination of the neuroscience behind Buddhist meditation and insight.
  3. Lutz, A., Greischar, L.L., Rawlings, N.B., Ricard, M., & R.J. Davidson. “Long-term meditators self-induce high-amplitude gamma synchrony during mental practice.” Proc Natl Acad Sci. 2004; 101(46): 16369-73.
    This paper describes the study in which Davidson’s lab used EEG testing on Buddhist monks and novices. It is fairly easy to read, but it does go into detail about high amplitude gamma waves and synchronizations.
  4. Thitavanno, Pichitr. A Buddhist Way of Mental Training. (Self-Published). 2002
    This book was written by a Buddhist monk and it describes the Buddhist philosophy, as well as the basics of mental training.
  5. http://www.crystalinks.com/medbrain.html
    This site describes the various types of brain waves and also contains several news articles about the relationship between meditation and the brain.
  6. http://www.mindandlife.org/
    The Mind and Life Institute is dedicated to creating a powerful working collaboration and research partnership between modern science and Buddhism: the world’s two most powerful traditions for understanding the nature of reality and investigating the mind. Contains links to articles, conferences and events, news articles, books, and research initiatives
  7. Wallace, Alan. Buddhism and Science: Breaking New Ground. Columbia University Press, NY: 2003.
    This book brings together distinguished philosophers, Buddhist scholars, physicists, and cognitive scientists to examine the contrasts and connections between the worlds of Western science and Eastern spirituality.


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

My Friend has Huntington's Disease – How can I help?

Here at HOPES we get many e-mails asking “What can I do for my friend or loved one that has been diagnosed with HD?” The answer, of course, is not simple and will be unique for every situation. But here are some ways that you might start to help someone you care about.

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Things you can do to help someone with HD:

  1. Give them hope! – Let them know you want to be there for them.
    1. Help them relax and realize that HD doesn’t have to completely dominate their life.
    2. Help them maintain a sense of normalcy. This can be as easy as going for a walk or getting coffee with them regularly.
  2. Give them HOPES! – By helping them learn about what they are up against, you can help turn a scary, unknown enemy into a target that they can pin down.
    1. Help them figure out what kinds of questions they have, and help them find the answers on the HOPES website.
    2. Educate yourself, so that you can support them in an informed way, with a better understanding of the battles they are fighting.
    3. Contact us here at HOPES via e-mail – we’re glad to help in anyway we can.
  3. Refer them to organizations that can help them connect to the HD community and keep up to date on the latest developments in HD research.
    1. Find the Huntington’s Disease Advocacy Center (HDAC), a site by HD families for HD families, here: http://www.hdac.org
    2. Find the HD Lighthouse, a site dedicated to providing information on the latest information scientific trials about HD, here: http://www.hdlighthouse.org
  4. Get them in contact with a support group in their area through the Huntington’s Disease Society of America (HDSA).
    1. To find a support group in your area, look here.
  5. Help them get in contact or maintain contact with a physician that understands Huntington’s Disease.
    1. There are Centers of Excellence that specialize in managing HD all around the country. For more information about Centers of Excellence, click here.
    2. To find a Center of Excellence in your area, click here.
  6. Find out what they need to help combat the disease:
    1. People in the beginning stages may not have any physical difficulties, but may need emotional support and someone to help them make sense of their mood swings or other emotional difficulties.
    2. In later stages of the disease, people with HD may need more help getting places due to the muscle spasms that the disease can cause. A trip to the grocery store or the dry cleaners on their behalf could be a great help.
    3. People that have had the disease for quite a while may need help with more basic tasks, like maintaining their personal hygiene, cooking, or keeping their house in order.
  7. Help them plan for the future:
    1. It may be important to have someone ready to make health care decisions should someone with HD be unable to make those decisions themselves – Learn more about becoming a Health Care Surrogate on the Florida Suncoast Hospice site here.
    2. Completing a living will is an important step in confronting the challenges that HD presents: Learn more about living wills from the Florida Suncoast Hospice site here.

We understand that the challenge may seem daunting when you’re trying to help someone with Huntington’s Disease, but even a little gesture can mean a lot. It is so important that people with HD have friends and family that care about them, and just being there to help them forget about their HD for a while. At the same time, it’s important not to overwhelm yourself as a caregiver, so make sure to take care of yourself as well. Together, people with HD and their caregivers are a powerful team against HD!

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The Mediterranean Diet

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The Mediterranean diet, based on the dietary habits of the people of Crete, has become more popular to scientists and consumers, as studies continue to reveal its health benefits. For instance, studies show that the diet increases longevity and decreases the risk of Alzheimer’s disease. These promising results would suggest that studies investigating how the Mediterranean diet affects HD patients would be of interest the HD community. This chapter first discusses the history of the Mediterranean diet, what the diet consists of, and then explains in more detail the results of the diet’s studies.

How was the Mediterranean diet discovered?^

Dr. Ancel Keys and his colleagues were the first to discover that the Mediterranean diet has health benefits for a wide range of diseases. During the early 1950s and late 1960s, while Keys was investigating his hypothesis, the Mediterranean region was recovering from the effects of World War II but was not yet influenced by the rising trend of fast food. Keys formed his hypothesis from his simple observation that the people of the island Crete were in especially good health, largely due to their dietary habits.

What is the Mediterranean diet?^

The ideal Mediterranean diet is based on the dietary patterns of the people of Crete in the early 1950s and late 1960s. The Mediterranean diet, as the name expresses, is characteristic of the foods that are commonly available in this region. For instance, the olive-rich Mediterranean makes it easy and common for the people to include olive oil abundantly in their diet.

The Mediterranean diet consists of 9 parts:

  1. High consumption of monounsaturated fat (mostly in the form of olive oil), rather than saturated fats
    • Examples of foods high in monounsaturated fat are olive oil, canola oil, peanut oil, sesame oil, sunflower oil, and avocados.
    • Examples of foods high in saturated fat are butter, lard, meat, dairy products, coconut oil, and palm kernel oil.
  2. Regular and moderate consumption of alcohol, in the form of red wine during meals.
    • If you are a woman (or a man over age 65), moderate consumption is less than one 5-ounce glass of red wine per day.
    • If you are a man under age 65, moderate consumption is less than two 5-ounce glasses of red wine per day.
    • Drinking over this consumption level can result in increased risk of some cancers.
    • The diet’s regular and moderate consumption of alcohol is not for everyone. If you do not normally drink alcohol, you do not need to start drinking. Do not drink alcohol if your doctor advises you not to do so.
    • To read more about the benefits of red wine, please click here.
  3. High consumption of legumes, nuts, and seeds
    • Examples of legumes are beans, peas, alfalfa, lentils, and peanuts. Nuts, such as almonds, pecans, and walnuts, are low in unsaturated fat but high in calories, so it is recommended to only eat about a handful of nuts per day.
  4. High consumption of non-refined cereals and breads
    • Non-refined cereals and breads incorporate the whole grain (including its bran and germ) into the food product, such that you gain the benefit of the grain’s high fiber. Examples of non-refined cereals and breads are brown rice, popcorn, oatmeal, whole wheat bread, whole wheat flour, whole wheat pasta, bran flakes, and rice cakes.
    • Refined cereals and breads means that the portion of the grain that provides its high fiber (its bran and germ) are removed by machinery. Examples of refined cereals and breads are white bread, white rice, pasta, and sugary cereals.
  5. High consumption of fruits
  6. High consumption of vegetables
  7. Low to moderate consumption of dairy products, mostly in the form of cheese or yogurt
  8. Low consumption of meat and poultry
  9. Moderate to high consumption of fish
    • Fish contain healthy omega-3 fatty acids that are thought to act against the inflammatory effects that exacerbate HD. To learn more about omega-3 fatty acids and HD, please click here.

The Mediterranean Diet Food Pyramid

Remember to stay hydrated, and replace salt with herbs, such as oregano and basil (e.g. oregano, basil, thyme, etc.)

Figure Source: Trichopoulou A. Traditional Mediterranean diet and longevity in the elderly: a review. Public Health Nutrition. 2004 Oct;7(7):943-7. Review.


Why choose the Mediterranean diet?^

Easily adaptable into your lifestyle^

Dietary recommendations for our health often involve the increased consumption of certain nutrients, such as particular vitamins and minerals. However, the Mediterranean diet is different in that it is a dietary pattern, rather than the supplementation of a several nutrients. The benefit of the dietary pattern is that is more easily adaptable to one’s lifestyle, since people normally eat a range of different foods in different amounts, as opposed to the very high consumption of certain nutrients. Furthermore, the foods outlined in the Mediterranean diet are foods that many of us already typically include in our diets. Thus, adhering to the Mediterranean diet would not involve drastically changing from your current dietary habits. Rather, following the Mediterranean diet would translate into cutting down on some foods (such as refined cereals and meat) and changing the portion of foods that you already eat (such as increasing consumption of olive oil and fish). Additionally, studies have shown that the Mediterranean diet is also beneficial to ethnic populations different from those that reside in the Mediterranean area.

Since the Mediterranean diet is a dietary pattern, it is often difficult for scientists to determine exactly which parts of the diet are most beneficial, or which parts could even possibly be harmful. However, the scientific community generally believes that the benefits gained from the diet are not due to one single part of the diet. For example, Scarmeas et al reported that those who had high adherence to the Mediterranean diet were less likely to develop Alzheimer’s disease, with no isolated part of the diet significantly being associated with this health benefit. This finding supports Scarmeas’ hypothesis that “composite dietary patterns can capture dimensions of nutrition that may be missed by individual components.”

Scientific Discoveries of Its Health Benefits^

Although a direct benefit of the Mediterranean diet to HD has not yet been discovered, many studies report benefits of the Mediterranean diet that may be of interest to those with HD, as well as the general population.

Many studies on longevity have found that elderly individuals who follow the Mediterranean diet live longer. For instance, in studies that have taken place among elderly populations in locations such as Greece, Spain, Denmark, and Australia, all participants experienced longevity due to following the Mediterranean diet (see review, Trichopoulou et al). One study, conducted by Knoops et al, showed that elderly individuals, 70 to 90 years old who adhered to the Mediterranean diet and a healthy lifestyle had a lower rate of all-causes and cause-specific mortality by more than a 50% compared to those individuals who were not on the diet. Cause-specific mortality was defined here as mortality due to coronary heart disease, cardiovascular disease, and cancer. However, it must be noted that this mortality statistic is based on not only the Mediterranean diet but also on a healthy lifestyle. Healthy lifestyle was defined by moderate alcohol consumption, nonsmoking, and physical activity. A similar study by Trichopulou et al that measured only the Mediterranean diet’s effect on longevity, with no reference to healthy lifestyle, confirms the findings in the Knoops study.

Perhaps of more interest to those with HD is the finding that adherence to the Mediterranean diet reduces cognitive decline and the risk of Alzheimer’s disease. Panza et al discovered that the Mediterranean diet protected against cognitive decline associated with normal aging of healthy individuals as well as cognitive impairment that characterizes Alzheimer’s disease and vascular disease. One of their results was that those who drank moderate amounts of wine had a lower risk of dementia of Alzheimer’s or vascular origin than those who did not drink any. Similarly, Scarmeas et al found that the group of people that most closely adhered to the Mediterranean diet (highest tertile in scores) reduced their risk of getting Alzheimer’s disease by 40%, compared to those of the lowest tertile in adherence scores.

One of the hypotheses as to how the Mediterranean diet benefits those with Alzheimer’s disease is that the diet protects against inflammation and oxidative stress, which are also thought to be common complications of Huntington’s disease. (For information on inflammation in HD, please click here and for information on oxidative stress and HD please click here.) Consequently, the Mediterranean diet may be helpful in preventing the progression of HD. Studies investigating the specific effects of the Mediterranean diet on HD still need to be conducted.

For further reading^

  • Kawas CH. Comment on Diet and the Risk of Alzheimer’s Disease (Scarmeas). Ann Neurol. 2006 Jun;59(6):877-9.
    This commentary article critiques the successes and limitations of Scarmeas’ study.
  • Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA. 2004 Sep 22;292(12)1433-9.
    This article found that elderly of ages 70-90 decreased by 50% all-causes mortality and cause-specific mortality by following a healthy lifestyle and Mediterranean diet.
  • Mayo Clinic. Mediterranean diet for heart health . June 21, 2006. http://www.mayoclinic.com/health/mediterranean-diet/CL00011
    This article gives additional examples of which foods satisfy the Mediterranean diet’s requirements.
  • Panza F, Solfrizzi V, Colacicco AM, D’Introno A, Capurso C, Torres F, Del Parigi A, Capurso S, Capurso A. Mediterranean diet and cognitive decline . Public Health Nutr. 2004 Oct;7(7):959-63. Review.
    This article is a little more difficult to understand than the rest. The article discusses the finding that the Mediterranean diet protects against cognitive decline of normal aging as well as that of Alzheimer’s disease and vascular disease.
  • Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean Diet and Risk for Alzheimer’s Disease . Ann Neurol. 2006 Jun;59(6):912-21.
    This article is fairly easy-to-read and details how high adherence to the Mediterranean diet is associated with lowered risk of Alzheimer’s disease.
  • Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003 Jun 26;348(26):2599-608.
    This easy-to-read article finds that close adherence to the Mediterranean diet is associated with decreased all-causes mortality and mortality specially caused by cancer and coronary heart disease.
  • Trichopoulou A. Traditional Mediterranean diet and longevity in the elderly: a review. Public Health Nutr. 2004 Oct;7(7):943-7. Review.
    This article is a literature review of several studies investigating the effects of the Mediterranean diet on longevity in the elderly. The article’s language is clear, and the Mediterranean diet was found to increase longevity in the elderly living in Greece , Spain , Denmark , and Australia .
  • Vanitallie TB. Ancel Keys: a tribute. Nutr Metab (Lond). 2005 Feb 14;2(1):4.
    Details the life of Ancel Keys, the founder of the Mediterranean diet.

-C. A. Chen 5-7-07

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Stress and Huntington's Disease

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Stress-and-HD

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^

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^

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

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Driving and Huntington's Disease

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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
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About Diet and Huntington’s Disease

In addition to the medications that we all get at a pharmacy, another large influence on human health can also be found in the marketplace… at the grocery store! One’s diet can have an immense influence on everything from energy level to the ability to fight diseases. Because of the immense importance of nutrition, HOPES has developed this chapter to discuss some of the various foods and eating practices that can have both a general health-promoting effect, and also special benefits for people coping with Huntington’s disease.

Many of the food and eating practices discussed in this section are still being researched, and so just as with HD treatments, please always consult a physician to see if a particular food or eating practice is right for you.

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Complementary and Alternative Medicine

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

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