Category: Sleep Disorders

When people finish treatment for cancer, they want to bounce back to their former vital selves as quickly as possible. But a new Northwestern Medicine study — one of the largest survivor studies ever conducted — shows many survivors still suffer moderate to severe problems with pain, fatigue, sleep, memory and concentration three to five years after treatment has ended.

"We were surprised to see how prevalent these symptoms still are," said study co-investigator Lynne Wagner, an associate professor of medical social sciences at Northwestern University Feinberg School of Medicine and a clinical health psychologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "This is one of the first looks at what's really happening for survivors in terms of symptoms and treatment among community-based treatment settings across the U.S."

The persistent pain in survivors who are cancer-free and no longer receiving any treatment is particularly puzzling, Wagner noted, because good treatment exists. "It seems we haven't come a long way in managing pain despite a lot of medical advances, " she said. "This is eye opening. It tells us we need to be better in clinical practice about managing our survivors' pain."

Wagner is presenting the findings at the 2011 American Society of Clinical Oncology Annual Meeting in Chicago. June 5 is National Cancer Survivors Day.

Cancer survivors seem to slip through the cracks in healthcare in terms of getting treatment for their pain and other symptoms.

"We don't have a great system to provide care to cancer survivors," Wagner said. "Cancer survivors are left trying to put the pieces together to find optimal care. They ideally need to see someone who is knowledgeable about the long-term affects of treatment." She pointed to the example of the STAR (Survivors Taking Action & Responsibility) Survivorship Program at Lurie Cancer Center, a comprehensive long-term follow-up program for survivors of pediatric cancer.

The study included a sample of 248 survivors of breast, colorectal, lung and prostate cancer. The survivors were primarily female and white, and most were more than five years post-diagnosis. They also had been treated in community settings — where 80 percent of people with cancer are treated in the United States — as opposed to academic medical centers. This group best represents the typical experience of cancer survivors around the country, Wagner said.

The most common symptoms reported by survivors were fatigue (16 percent), disturbed sleep (15 percent), cognitive difficulties (13 percent) and pain (13 percent.)

Survivors need education programs for transitioning from treatment to life as a cancer survivor, and this education should include skills for managing these difficult and chronic symptoms, Wagner said. Medical providers also need to be educated about survivors' lingering symptoms.

"It is acceptable for someone actively going through cancer treatment to have pain medications, but when they transition to being survivors, that acceptance goes away," Wagner said. "If they ask for pain medication again, doctors may worry that they are getting addicted."

The study also pointed out the need to develop better ways to address sleep problems, fatigue and lasting difficulties with memory and concentration. Non-drug interventions for improving sleep are effective, Wagner said, and researchers need to tailor these for cancer survivors.

Exercise is the most effective weapon against cancer-related fatigue, but it's challenging to adhere to an exercise regime when you don't feel well. "We need to see how we can be more effective in promoting physical activity among survivors," Wagner said.

Researchers also documented any treatment interventions for study participants' symptoms and then repeated an assessment of the symptoms four weeks later.

"We generally found the same severity of these symptoms one month later, suggesting they tend to be chronic," Wagner said.

The study stemmed from a 2002 National Cancer Institute meeting on pain, fatigue and depression in cancer. Participants concluded more research was needed on the prevalence of these symptoms.

The study was funded by the Eastern Cooperative Oncology Group, which is funded primarily by the National Institute of Cancer.

A protein that helps the brain develop early in life can fight the mental fuzziness induced by sleep deprivation, according to researchers at Washington University School of Medicine in St. Louis.

"It's interesting that NOTCH, a protein that plays such a prominent role in development, also has important functions in the adult brain," says senior author Paul Shaw, PhD, associate professor of neurobiology. "To our surprise, we found if NOTCH activity is boosted in the brains of sleep-deprived fruit flies, the flies can continue to stay sharp and learn after sleep deprivation. They behave as if they had a full night's sleep."

Shaw studies interactions between sleep and learning to develop treatments that help the brain resist the mental impairments imposed by sleep deprivation. He wants to assist people forced to work with minimal sleep, such as members of the military or disaster relief workers.

The findings appear online May 5 in Current Biology.

Shaw and his colleagues test flies' ability to learn by pairing a negative stimulus (the chemical quinine, which flies prefer to avoid) with a positive stimulus (a light, which flies instinctively seek). When offered an opportunity to enter a darkened tube or a lighted tube with quinine, flies that can learn suppress their natural desire to choose the light. Flies, like humans, show a progressive decline in cognitive performance during the course of a typical waking day. Prolonged disruption of sleep causes a much sharper drop in learning.

Shaw became interested in NOTCH when his group found that sleep deprivation in flies caused increased activity in a gene that suppresses NOTCH. They found a similar increase in humans following sleep loss. They went on to show that when that suppressor is genetically disabled, allowing increased NOTCH activity, flies continue to learn even when sleep-deprived.

To further confirm NOTCH's involvement in these processes, Shaw and lead author Laurent Seugnet, PhD, a researcher now at the Lyon Neuroscience Research Center in Lyon, France, analyzed where NOTCH is made in the brain. They found that in adult fruit flies, specialized brain cells known as glia make NOTCH. Scientists have typically regarded glia as passive support cells that merely nourish and supply neurons, the cells that do the "work" of the brain. According to Shaw, though, this study and others have scientists reconsidering how actively glia may be involved in certain mental processes, including sleep.

"We may want to target glia to reduce or slow the cognitive deficits associated with increased wakefulness, allowing people such as emergency personnel and air traffic controllers to stay awake and functional for extended periods of time," Shaw says. "If modifying glia can slow negative outcomes associated with prolonged wakefulness, that may provide us with a more natural way of helping people stay awake than directly targeting neurons."

Seugnet L, Suzuki Y, Merlin G, Gottschalk L, Duntley SP, Shaw PJ. Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila. Current Biology, May 5, 2011.

Funding from the McDonnell Center for Cellular and Molecular Neurobiology and the National Institutes of Health (NIH) Neuroscience Blueprint Core Grant supported this research.

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Journal Reference:

1. Laurent Seugnet, Yasuko Suzuki, Gabriel Merlin, Laura Gottschalk, Stephen P. Duntley, Paul J. Shaw. Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila. Current Biology, May 5, 2011 DOI: 10.1016/j.cub.2011.04.001

Sleeping worms have much to teach people, a notion famously applied by the children's show "Sesame Street," in which Oscar the Grouch often reads bedtime stories to his pet worm Slimy. Based on research with their own worms, a team of neurobiologists at Brown University and several other institutions has now found that "Notch," a fundamental signaling pathway found in all animals, is directly involved in sleep in the nematode C. elegans.

"This pathway is a major player in development across all animal species," said Anne Hart, associate professor of neuroscience at Brown. "The fact that this highly conserved pathway regulates how much these little animals sleep strongly suggests that it's going to play a critical role in other animals, including humans. The genes in this pathway are expressed in the human brain."

The work, to be published May 24 in the journal Current Biology, offers new insights into what controls sleep. The lead authors are Komudi Singh, a postdoctoral fellow in the Department of Neuroscience at Brown University, and Michael Chao, a previous member of the Hart laboratory, who is now an associate professor at California State University-San Bernardino.

"We understand sleep as little as we understand consciousness," said Hart, the paper's senior author. "We're not clear why sleep is required, how animals enter into a sleep state, how sleep is maintained, or how animals wake up. We're still trying to figure out what is critical at the cellular level and the molecular level."

Ultimately, Hart added, researchers could use that knowledge to develop more precise and safer sleep aids.

"We only have some really blunt tools that we can use to change sleep patterns," she said. "But there are definite side effects to manipulating sleep the way we do now."

Mysterious napping

Hart first realized that Notch pathway genes might be important for sleep when her group was investigating an entirely different behavior. She was studying the effect of this pathway on the nematodes' revulsion to an odious-smelling substance called octanol. What she found, and also reports in the Current Biology paper, is that adult nematodes without Notch pathway genes (like osm-11) have their Notch receptors turned off and, therefore, they do not avoid octanol as normal worms do.

But she was shocked to find that the adult nematodes in which the osm-11 gene was overexpressed were doing something quite bizarre. "Normally, adult nematodes spend all of their time moving" she said. "But, these animals suddenly start taking spontaneous 'naps.' It was the oddest thing I'd seen in my career."

Nematode sleep is not exactly the same as sleep in larger animals, but these worms do go into a quiescent sleep-like state when molting. The worms with too much osm-11 were dozing when they were not supposed to.

Other experiments showed that worms lacking osm-11 and the related osm-7 genes were hyperactive, exhibiting twice as many body bends each minute as normal nematodes.

The story became clear. The more Notch signaling was turned on, the sleepier the worms would be. When it is suppressed, they go into overdrive and become too active.

In humans, the gene that is most similar to osm-11 is called Deltalike1 (abbreviated DLK1). It is expressed in regions of the brain associated with the sleep-wake cycle.

Beyond Notch

That result alone is not enough to lead directly to the development of a new sleep drug, even for worms. Notch signaling is implicated in a lot of different activities in the body, Hart said, some of which should not be encouraged.

"Too much Notch signaling can cause cancer, so we would have to be very targeted in how we manipulate it," she said. "One of the next steps we're going to take is to look at the specific steps in Notch signaling that are pertinent to arousal and quiescence."

Focusing on those steps could minimize side effects, Hart said.

In addition to Hart, Singh, and Chao, other authors from Brown were Mark Corkins, Melissa Walsh, and Emma Beaumont, an intern from University of Bath. Authors who worked at Massachusetts General Hospital were Gerard Somers, Hidetoshi Komatsu, Jonah Larkins-Ford, Tim Tucey, and Heather Dionne. Author Douglas Hart is from the Massachusetts Institute of Technology and author Shawn Lockery is from the University of Oregon.

The National Institutes of Health and Massachusetts General Hospital funded the research.

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Journal Reference:

1. Komudi Singh, Michael Y. Chao, Gerard A. Somers, Hidetoshi Komatsu, Mark E. Corkins, Jonah Larkins-Ford, Tim Tucey, Heather M. Dionne, Melissa B. Walsh, Emma K. Beaumont, Douglas P. Hart, Shawn R. Lockery, and Anne C. Hart. C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence. Current Biology, 2011; DOI: 10.1016/j.cub.2011.04.010

Staying up late every night and sleeping in is a habit that could put you at risk for gaining weight. People who go to bed late and sleep late eat more calories in the evening, more fast food, fewer fruits and vegetables and weigh more than people who go to sleep earlier and wake up earlier, according to a new Northwestern Medicine study.

Late sleepers consumed 248 more calories a day, twice as much fast food and half as many fruits and vegetables as those with earlier sleep times, according to the study. They also drank more full-calorie sodas. The late sleepers consumed the extra calories during dinner and later in the evening when everyone else was asleep. They also had a higher body mass index, a measure of body weight, than normal sleepers.

The study is one of the first in the United States to explore the relationship between the circadian timing of sleeping and waking, dietary behavior and body mass index. The study was published online in the journal Obesity and is expected to appear in a late summer print issue.

"The extra daily calories can mean a significant amount of weight gain — two pounds per month — if they are not balanced by more physical activity," said co-lead author Kelly Glazer Baron, a health psychologist and a neurology instructor at Northwestern University Feinberg School of Medicine.

"We don't know if late sleepers consume the extra calories because they prefer more high-calorie foods or because there are less healthful options at night," said co-lead author Kathryn Reid, research assistant professor in neurology at the Feinberg School.

The study shows not only are the number of calories you eat important, but also when you eat them — and that's linked to when you sleep and when you wake up, noted senior author Phyllis Zee, M.D., professor of neurology and director of the Sleep and Circadian Rhythms Research Program at Feinberg and medical director of the Sleep Disorders Center at Feinberg and Northwestern Memorial Hospital.

"Human circadian rhythms in sleep and metabolism are synchronized to the daily rotation of the Earth, so that when the sun goes down you are supposed to be sleeping, not eating," Zee said. "When sleep and eating are not aligned with the body's internal clock, it can lead to changes in appetite and metabolism, which could lead to weight gain."

The research findings could be relevant to people who are not very successful in losing weight, Zee said. "The study suggests regulating the timing of eating and sleep could improve the effectiveness of weight management programs," she said.

The findings also have relevance for night-shift workers, who eat at the wrong time of day related to their bodies' circadian rhythms. "It's midnight, but they're eating lunch," Zee said. "Their risk for obesity as well as cardiovascular, cerebrovascular and gastrointestinal disorders is higher."

The study included 51 people (23 late sleepers and 28 normal sleepers) who were an average age of 30. Late sleepers went to sleep at an average time of 3:45 a.m., awoke by 10:45 a.m., ate breakfast at noon, lunch at 2:30 p.m., dinner at 8:15 p.m. and a final meal at 10 p.m. Normal sleepers on average were up by 8 a.m., ate breakfast by 9 a.m., lunch at 1 p.m., dinner at 7 p.m., a last snack at 8:30 p.m. and were asleep by 12:30 a.m.

Participants in the study recorded their eating and sleep in logs and wore a wrist actigraph, which monitors sleep and activity cycles, for at least seven days.

Late sleepers function in society by finding jobs where they can make their own hours, Baron noted, such as academics or consultants. "They find niches where they can live this lifestyle, or they just get by with less sleep," she said.

Northwestern researchers are planning a series of studies to test the findings in a larger community and to understand the biological mechanisms that link the relationship between circadian rhythms, sleep timing and metabolism.

The research was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health.

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Journal Reference:

1. Kelly G. Baron, Kathryn J. Reid, Andrew S. Kern, Phyllis C. Zee. Role of Sleep Timing in Caloric Intake and BMI. Obesity, 2011; DOI: 10.1038/oby.2011.100

 In the largest study of it kind to establish a link between sleep and diabetes, researchers found that people with diabetes who sleep poorly have higher insulin resistance, and a harder time controlling the disease.

The findings, published in the June issue of Diabetes Care, suggest that poor sleep may contribute to worse outcomes in people with diabetes.

"Poor sleep quality in people with diabetes was associated with worse control of their blood glucose levels," said Kristen Knutson, PhD, assistant professor of medicine and lead author of the study. "People who have a hard time controlling their blood glucose levels have a greater risk of complications. They have a reduced quality of life. And, they have a reduced life expectancy."

People with diabetes generally have poorer sleep than the general population, and poor sleep has been proposed as a risk factor for developing the disease. Sleep disorders, such as obstructive sleep apnea, are more prevalent in people with type 2 diabetes, Knutson said.

For the study, researchers monitored the sleep of 40 people with diabetes for six nights. The subjects also reported if they generally suffered from symptoms of sleep disturbances like insomnia, snoring or sleep apnea. At clinical examinations, they gave blood samples to allow researchers to measure insulin and glucose levels.

The subjects wore activity monitors on their wrists at night, which measure their wrist movements throughout the night. Poor sleep, or insomnia, was determined by both poor sleep quality based on the activity monitors and the subject telling the researchers that they often had a hard time falling asleep or woke up during the night.

Among the diabetics, poor sleepers had 23% higher blood glucose levels in the morning, and 48% higher blood insulin levels. Using these numbers to estimate a person's insulin resistance, the researchers found that poor sleepers with diabetes had 82% higher insulin resistance than normal sleepers with diabetes.

Knutson said the next step for researchers is to see if treating poor sleep can improve long-term outcomes and quality of life for diabetics. "For someone who already has diabetes, adding a sleep treatment intervention, whether it's treating sleep apnea or treating insomnia, may be an additional help for them to control their disease," Knutson said.

In fact, restoring a healthy amount of sleep may be as powerful an intervention as the drugs currently used to treat type 2 diabetes. "This suggests that improving sleep quality in diabetics would have a similar beneficial effect as the most commonly used anti-diabetes drugs," said Eve Van Cauter, PhD, professor of medicine and co-author of the study.

Further investigation into which leads to the other — the chronic poor sleep or chronic insulin resistance — could improve the quality of life for people with type 2 diabetes. "Anything that we can do to help people improve their ability to control their glucose will help their lives in the long run," Knutson said.

The data was collected as part of the CARDIA study, an ongoing longitudinal study of the heart health. It has tracked thousands of people for over 20 years.

The study, "Cross-sectional associations between measure of sleep and markers of glucose metabolism among persons with and without diabetes" was published online March 16, 2011, in the journal Diabetes Care. In addition to Drs. Knutson and Van Cauter, authors include Phyllis Zee and Kiang Liu at Northwestern University, and Diane Lauderdale at the University of Chicago Department of Health Studies.

The research was funded by a grant from the National Institute on Aging at the U.S. National Institutes of Health. The CARDIA study is supported by the National Heart, Lung, and Blood Institute.

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Journal Reference:

1. K. L. Knutson, E. Van Cauter, P. Zee, K. Liu, D. S. Lauderdale. Cross-Sectional Associations Between Measures of Sleep and Markers of Glucose Metabolism Among Subjects With and Without Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study. Diabetes Care, 2011; 34 (5): 1171 DOI: 10.2337/dc10-1962

A study in the April 15 issue of the Journal of Clinical Sleep Medicine shows increased automobile crash rates among teen drivers who start school earlier in the morning.

Results indicate that in 2008 the weekday crash rate for 16- to 18-year-olds was about 41 percent higher in Virginia Beach, Va., where high school classes began at 7:20 — 7:25 a.m., than in adjacent Chesapeake, Va., where classes started at 8:40 — 8:45 a.m. There were 65.8 automobile crashes for every 1,000 teen drivers in Virginia Beach, and 46.6 crashes for every 1,000 teen drivers in Chesapeake. Similar results were found for 2007, when the weekday crash rate for Virginia Beach teens (71.2) was 28 percent higher than for Chesapeake teens (55.6). In a secondary analysis that evaluated only the traditional school months of September 2007 through June 2008, the weekday crash rate for teen drivers was 25 percent higher in Virginia Beach (80.0) than in Chesapeake (64.0). An investigation of traffic congestion in the neighboring cities did not reveal differences that might account for the teen crash findings.

"We were concerned that Virginia Beach teens might be sleep restricted due to their early rise times and that this could eventuate in an increased crash rate," said lead author Robert Vorona, MD, associate professor of internal medicine at Eastern Virginia Medical School in Norfolk, Va. "The study supported our hypothesis, but it is important to note that this study does not prove cause and effect. We are planning to perform subsequent studies to follow up on these results and to investigate other potential ramifications of early high school start times."

According to the American Academy of Sleep Medicine, the average teen needs a little more than nine hours of sleep each night. However, chronic sleep restriction is a common problem among teens. During adolescence, a biological change shifts the typical onset of sleepiness later at night. This delay can make it a challenge for teens to get enough sleep when they have to wake up early for school.

Vorona says that starting high school later in the morning may promote driver alertness by allowing teens to get more sleep at night.

"We believe that high schools should take a close look at having later start times to align with circadian rhythms in teens and to allow for longer sleep times," he said. "Too many teens in this country obtain insufficient sleep. Increasingly, the literature suggests that this may lead to problematic consequences including mood disorders, academic difficulties and behavioral issues."

Another study in the April issue of the Journal of Clinical Sleep Medicine suggests that delaying school start times by one hour could enhance students' cognitive performance by improving their attention level and increasing their rate of performance, as well as reducing their mistakes and impulsivity. The Israeli study of 14-year-old, eighth-grade students found that the teens slept about 55 minutes longer each night and performed better on tests that require attention when their school start time was delayed by one hour.

Vorona's study involved data provided by the Virginia Department of Motor Vehicles. In Virginia Beach, there were 12,916 registered drivers between 16 and 18 years of age in 2008, and these teen drivers were involved in 850 crashes. In Chesapeake there were 8,459 teen drivers and 394 automobile accidents. The researchers report that the two adjoining cities have similar demographics, including racial composition and per-capita income.

Further analysis by time of day found that, in the morning, the teen crash rates peaked when students would be commuting to school, from 7 a.m. to 7:59 a.m. for Virginia Beach and 8 a.m. to 8:59 a.m. for Chesapeake. Teen crash rates were highest in the afternoon hours, from 2 p.m. to 6 p.m. in Virginia Beach, where schools dismissed at about 2 p.m., and from 4 p.m. to 7 p.m. in Chesapeake, where schools dismissed between 3 p.m. and 3:45 p.m.

The study was supported by the Eastern Virginia School of Medicine Division of Sleep Medicine. Vorona presented the preliminary results of the study as an oral abstract last June at SLEEP 2010 in San Antonio, Texas.

Read more from the AASM about teens and school start times at http://www.sleepeducation.com/Topic.aspx?id=42.

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Journal Reference:

1. Robert Daniel Vorona, Mariana Szklo-Coxe, Andrew Wu, Michael Dubik, Yueqin Zhao, J. Catesby Ware. Dissimilar Teen Crash Rates in Two Neighboring Southeastern Virginia Cities with Different High School Start Times. Journal of Clinical Sleep Medicine, 2011; 7 (2): 145-151

Fatigue and sleep problems dramatically reduce the thinking and reasoning abilities of adults who survived childhood cancer, according to new research from the Childhood Cancer Survivor Study. Researchers hope the findings will lead to new strategies for improved neurocognitive functioning in this growing population. The work was led by St. Jude Children's Research Hospital investigators.

This is the first study to show that childhood cancer survivors are particularly vulnerable to impaired memory, emotional control, organization and related neurocognitive skills due to fatigue and sleep problems. The link was independent of the survivor's age, sex or cancer treatment.

"While no one functions quite as well when sleep deprived or fatigued, most adults get by. But that is not always the case for survivors, who might already be at greater risk for neurocognitive problems as a result of their cancer treatment," said Kevin Krull, Ph.D., the study's corresponding author and an associate member of the St. Jude Department of Epidemiology and Cancer Control. St. Jude investigators led the study, results of which appear in the April 11 online edition of the journal Cancer.

The impact of sleep difficulties and fatigue on neurocognitive functioning, including the ability to think quickly, was comparable to side effects associated with high-dose cranial irradiation therapy, Krull said.

"Rates of sleep disturbance were not substantially higher among cancer survivors, but cancer survivors who are already at risk for cognitive problems have a three- to four-fold increase of those problems when they are sleep deprived or fatigued," Krull said. This study compared cancer survivors to healthy siblings. Impaired cognitive functioning was defined as scoring in the bottom 10 percent on validated tests that measure thinking and reasoning abilities.

"These problems can profoundly impact a survivor's life," said Krull. Cognitive problems make it less likely survivors will hold a job, live independently, marry or form other social connections. Despite years of work to overcome such treatment side effects, therapies are few and improvements modest. "The results from this study give us two more avenues to pursue and perhaps enhance the benefits of current therapies, including memory training," he said. At St. Jude, work has already begun.

Krull said the findings suggest survivors might benefit from periodic screenings for fatigue and sleep disturbances. The results might be useful for helping adult cancer survivors, who also battle fatigue, sleep difficulties and neurocognitive problems.

The work involved 1,426 survivors and 384 healthy siblings enrolled in the CCSS. The patients were found to have brain and central nervous system tumors, leukemia and lymphoma between 1970 and 1986 when they were age 20 or younger. Participants in this study completed several tests proven to reliably measure memory, organization, task efficiency and emotional regulation. All are indicators of neurocognitive functioning. The participants also completed questionnaires to measure fatigue, sleep quality, daytime sleepiness and vitality.

The CCSS is a collaboration that currently includes 30 U.S. and Canadian institutions. Funded by the National Cancer Institute, it is headquartered at St. Jude. The study's focus is long-term childhood cancer survivors and the goal is to help design therapies that maximize benefit and minimize risk.

Advances in childhood cancer treatment mean about 80 percent of patients today will become long-term survivors. But therapies also leave survivors at risk for a variety of problems. Particularly vulnerable for neurocognitive problems are those who were younger than age 6 when their cancer was found or those whose treatment included high-dose cranial irradiation, steroids or certain chemotherapy agents known as anti-metabolites.

Those risk factors cannot fully explain the neurocognitive variability seen among survivors. Designing more effective therapies requires better understanding of that variability. "There are likely multiple causes, which will require more individualized treatment approaches," Krull said.

More than 20 percent of survivors in this study had neurocognitive problems. Those at a two-fold higher risk of memory problems included survivors treated with high-dose cranial irradiation as well as those who scored highest on measures of daytime sleepiness and decreased vitality. Research found survivors with low vitality scores were three times more likely to have problems controlling their emotions. Fatigue and poor sleep quality were also linked to an increased risk of neurocognitive problems.

Anti-depressant medication was also associated with factors that contribute to cognitive functioning, including a 70 percent increased risk of memory problems and a 56 percent risk of reduced task efficiency. Krull said the link was independent of depression and needs further study.

There is good news. Exercise has helped patients battling chronic fatigue syndrome and other disorders counter the effects of fatigue. Krull said work is already underway at St. Jude to test the impact of exercise and measures to boost cognitive functioning with improved sleep.

Nancy Clanton, Ph.D., of St. Jude, is first author. The other authors are James Klosky, Chenghong Li, Neelam Jain, Deo Kumar Srivastava and Leslie Robison, all of St. Jude; Daniel Mulrooney, University of Minnesota; Lonnie Zeltzer, University of California, Los Angeles; and Marilyn Stovall, University of Texas, M.D. Anderson Cancer Center.

This work was supported in part by the National Cancer Institute and ALSAC.

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Journal Reference:

1. Nancy R. Clanton, James L. Klosky, Chenghong Li, Neelam Jain, Deo Kumar Srivastava, Daniel Mulrooney, Lonnie Zeltzer, Marilyn Stovall, Leslie L. Robison and Kevin R. Krull. Fatigue, vitality, sleep, and neurocognitive functioning in adult survivors of childhood Cancer : A report from the childhood cancer survivor study. Cancer, 11 April 2011 DOI: 10.1002/cncr.25797

The internally-driven daily cycle of blood pressure changes doesn't appear to be linked to the known increase in morning heart attacks, according to a study in Circulation Research: Journal of the American Heart Association.

Researchers sought to identify the role of the internal human body clock in the daily rise and fall in blood pressure. In the study, three groups of volunteers showed an internal daily blood pressure variation with a peak at around 9 p.m. — independent of changes in activity and other behavioral influences that can affect blood pressure.

Increased blood pressure is a major risk factor for adverse cardiovascular events. However, the study revealed that the internal blood pressure cycle resulted in the lowest blood pressure occurring in the late morning. This unexpected finding indicates that blood pressure's internal circadian rhythm — a cycle of about 24 hours that occurs in many biological processes — is unlikely to be linked to the well-documented morning peak in heart events or strokes, said Steven A. Shea, Ph.D., lead author of the study and associate professor of medicine at Harvard Medical School in Boston, Mass.

"We used three complementary experimental protocols and three different groups and found essentially the same results," Shea said. "That means we're dealing with something very robust."

Shea and his colleagues randomized 28 volunteers without hypertension to three multi-day in-laboratory protocols. Before the study, participants maintained a regular sleep-wake schedule at home (16 hours of scheduled wakefulness with eight hours of scheduled sleep) for two to three weeks to stabilize circadian rhythms. They then underwent two baseline days and nights in the laboratory with the same sleep-wake schedule as at home, followed by a prolonged laboratory protocol designed to separate internal circadian effects from behavioral and environmental effects on blood pressure and other physiological variables. These controlled behavioral and environmental conditions included activity, posture, meals, sleep, room temperature, and light. The researchers measured core body temperature to track circadian time.

The three protocols, carried out in dim light to avoid resetting any of the body's circadian rhythms, included:

• 38-hour "constant routine," with continuous wakefulness and constant body posture.
• 196-hour "forced desynchrony" (forcing a sleep/wake cycle to conflict with participants' normal pattern) consisting of recurring 28-hour sleep/wake cycles with 18 hours, 40 minutes awake and 9 hours, 20 minutes asleep.
• 240-hour "forced desynchrony" with twelve recurring 20-hour sleep/wake cycles.

All three protocols revealed almost identical systolic and diastolic circadian rhythms, which were unrelated to other internal rhythms that are known to influence cardiovascular events, such as increases in sympathetic nervous system activity.

The reason for the peak in heart attacks and strokes in morning hours remains unexplained by these findings, but could certainly be related to the activities that normally occur on a regular daily basis. "For example, other recent work by our group indicates that the body clock interacts with behaviors, such as exercise, to cause an exaggerated increase in cardiovascular risk markers during the biological morning," adds Frank A. Scheer, Ph.D., co-author of the study and assistant professor of medicine at Harvard Medical School. It is possible that the evening peak in the internal circadian blood pressure cycle may help to explain a second, albeit less prominent increase in heart attacks that occurs in the evening, the researchers said.

"We now need to study people with different vulnerabilities and risk factors for cardiovascular disease," Shea said. "So far, we have studied very healthy people who don't have hypertension or the build-up of arterial plaques that could bring them closer to the theoretical threshold for precipitating an adverse cardiac event."

Other co-authors are Michael F. Hilton, Ph.D.; Kun Hu, Ph.D.; and Frank A.J.L. Scheer, Ph.D.

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Journal Reference:

1. Steven A. Shea, Michael F. Hilton, Kun Hu, Frank A.J.L. Scheer. Existence of an Endogenous Circadian Blood Pressure Rhythm in Humans That Peaks in the Evening. Circulation Research, 2011 DOI: 10.1161/CIRCRESAHA.110.233668

Cave life is known to favor the evolution of a variety of traits, including blindness and loss of eyes, loss of pigmentation, and changes in metabolism and feeding behavior. Now researchers have added sleeplessness to that list.

Cave fish sleep significantly less than their surface counterparts, a finding by New York University biologists that reveals the genes involved in sleep patterns and disorders. Their study, which appears in the journal Current Biology, may shed light on how genetic makeup contributes to sleep variation and disruption in humans.

The study's authors were Erik Duboué, an NYU graduate student, Alex Keene, an NYU post-doctoral fellow, and Richard Borowsky, a professor in NYU's Department of Biology.

They examined surface fish in the species Astyanax mexicanus and three cave fish populations, Pachón, Tinaja and Molino, all of which inhabit northeast Mexico. While surface and cave fish have different physical appearances and behaviors — or phenotypes — brought about by evolutionary change, the researchers sought to determine whether the sleep patterns of cave fish also changed as they adapted to cave life.

To do so, they examined sleep patterns of both the surface and cave fish using two methods. In one, they determined that fish inactive for 60 seconds or more were sleeping. This conclusion was confirmed by tapping on the tank — fish inactive for this length of time were slow to respond to the tapping, a behavior consistent with being awoken from sleep. In the second, the researchers deprived the fish sleep as a way of inducing subsequent sleep behavior. When animals are deprived the chance to sleep, there is a rebound effect, so at the next opportunity, they sleep for longer than normal periods to make up for the deprivation. The researchers tested this rebound effect by disturbing the sleep of fish all night by moving their containers once a minute. When observed the next day, they slept significantly increased amounts of time.

Using these methods, the researchers found that, over a 24-hour period, surface fish slept an average of over 800 minutes while cavefish slept an average of between 110 to 250 minutes.

The researchers then sought to determine if genetics played a role in the varying sleep behaviors. To do this, they bred cave and surface fish and examined the sleep patterns of these hybrids. Their results showed that these hybrid fish nearly matched the sleep patterns of the cave fish, rather than those of the surface fish, demonstrating that cave fish carry a dominant gene for less sleep.

"In some ways, the sleep phenotypes of cave fish are similar to those of humans with sleep disorders," explained Borowsky. "They go to sleep, but only for relatively short periods, then they awaken and remain awake for relatively long periods."

"The next job is to identify the genes which are responsible for sleep modification in the cave fish. They would be good candidates for the genes responsible for insomnia and other sleep disorders in humans," he added.

The study was funded by grant from the National Science Foundation.

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Journal Reference:

1. Erik R. Duboué, Alex C. Keene, Richard L. Borowsky. Evolutionary Convergence on Sleep Loss in Cavefish Populations. Current Biology, 07 April 2011 DOI: 10.1016/j.cub.2011.03.020

A study in the April 1 issue of the journal Sleep suggests that the risk of death is more than two times higher in older adults who have sleep apnea and report struggling with excessive daytime sleepiness.

Results of adjusted proportional hazards modeling show that older adults with moderate to severe sleep apnea who reported struggling with excessive daytime sleepiness at baseline were more than twice as likely to die (hazard ratio = 2.28) as subjects who had neither problem. The risk of death was insignificant in older adults with only excessive daytime sleepiness (HR = 1.11) or sleep apnea (HR = 0.74). Participants had a mean age of 78 years at baseline, and about 55 percent (n = 160) died during an average follow-up period of 14 years.

"Excessive daytime sleepiness, when associated with sleep apnea, can significantly increase the risk of death in older adults," said principal investigator and lead author Dr. Nalaka S. Gooneratne, assistant professor of medicine in the University of Pennsylvania Health System in Philadelphia, Pa. "We did not find that being sleepy in and of itself was a risk. Instead, the risk of increased mortality only seemed to occur when sleep apnea was also present."

Gooneratne added that both daytime sleepiness and sleep apnea are common problems, with sleep apnea affecting up to 20 percent of older adults.

According to the American Academy of Sleep Medicine, the most common form of sleep apnea is obstructive sleep apnea, which occurs when soft tissue in the back of the throat collapses and blocks the upper airway during sleep. Older adults also are at risk for central sleep apnea, which involves a repetitive absence of breathing effort during sleep caused by a dysfunction in the central nervous system or the heart. Only four percent of participants had central sleep apnea, and there was no meaningful change in the results when they were excluded from the analysis.

The study involved 289 adults with neither dementia nor depression who were recruited from the community. Seventy-four percent were female. About half (n = 146) had significant levels of excessive daytime sleepiness at baseline, reporting that they felt sleepy or struggled to stay awake during the daytime at least three to four times a week. Sleep apnea was measured objectively by one night of polysomnography in a sleep lab. For analysis, participants were included in the sleep apnea group only if they had an apnea-hypopnea index of 20 or more breathing pauses per hour of sleep, which represents a moderate to severe level of sleep apnea.

Participants were recruited between 1993 and 1998. Survival status was determined by searching the social security death index, with follow-up ending Sept. 1, 2009.

According to the authors, the mechanism by which sleep apnea and excessive daytime sleepiness increase the risk of death is unclear. They suspect that inflammation may be involved, which could increase the risk of other medical problems such as hypertension. It also remains to be seen if treatment reduces the risk of death.

"Future research is needed to assess whether treating the sleep apnea can reduce mortality," said Gooneratne.

The treatment of choice for OSA is CPAP therapy, which provides a steady stream of air through a mask that is worn during sleep. This airflow keeps the airway open to prevent pauses in breathing and restore normal oxygen levels.

The study was supported by the National Institutes of Health through the National Institute on Aging and the National Center for Research Resources.

Help for people who have sleep apnea is available at more than 2,200 AASM-accredited sleep disorders centers across the U.S. An online directory of AASM-accredited sleep centers is available at www.sleepcenters.org.

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Journal Reference:

1. Nalaka S. Gooneratne, Kathy C. Richards, Marshall Joffe, Regina W. Lam; Fran Pack, Bethany Staley, David F. Dinges, Allan I. Pack. Sleep Disordered Breathing with Excessive Daytime Sleepiness is a Risk Factor for Mortality in Older Adults. Sleep, 2011; 34 (4): 435-442