Childhood Sleep Apnea Linked to Brain Damage, Lower IQ
In what is believed to be the first study showing neural changes in the brains of children with serious, untreated sleep apnea, Johns Hopkins researchers concluded that children with the disorder appear to suffer damage in two brain structures tied to learning ability.
Writing in the August 22 issue of the global online journal Public Library of Science Medicine, the Hopkins investigators said they compared 19 children with severe obstructive sleep apnea (OSA) to 12 children without the disorder. Using a special type of magnetic resonance imaging (MRI), researchers identified changes to the hippocampus and the right frontal cortex. Next, using IQ tests and other standardized tests that measure verbal performance, memory, and executive function, the researchers were able to link the changes in the two brain structures to deficits in neuropsychological performance.
The hippocampus, a structure in the temporal lobe, is vital to learning and memory storage, while the right frontal cortex governs higher-level thinking, such as accessing old memories and using them in new situations.
“This should be a wake-up call to both parents and doctors that undiagnosed or untreated sleep apnea might hurt children’s brains,” said lead author Ann Halbower, MD, a lung specialist at the Johns Hopkins Children’s Center. “This is truly concerning because we saw changes that suggest brain injury in areas of the brain that house critical cognitive functions, such as attention, learning, and working memory.”
While researchers have known for years that fragmented sleep, interrupted breathing, and oxygen deprivation—all hallmarks of sleep apnea—harm children’s learning ability and school performance, this is the first time they have linked changes in the brain’s chemistry to the syndrome in children, Halbower believed.
“We cannot say with absolute certainty that sleep apnea caused the injury, but what we found is a very strong association between changes in the neurons of the hippocampus and the right frontal cortex and IQ and other cognitive functions in which children with OSA score poorly,” Halbower said.
Children with OSA had lower mean IQ test scores (85) than children without OSA (101). Children with OSA also performed worse on standardized tests measuring executive functions, such as verbal working memory (8 versus 15) and word fluency (9.7 versus 12).
Using magnetic resonance spectroscopic imaging, which plots peak levels of brain chemicals in the form of graphs, researchers compared the ratios between each two of three chemicals—N-acetyl aspartate (NAA), creatine, and choline—in children with apnea and in those without. The hippocampus and the right frontal cortex of children with sleep apnea showed altered ratios of these neurochemicals that are not specific to any one disease but indicate injury to brain cells. Next, the researchers plan to study whether the ratios will return to normal once the sleep apnea is treated.
In both children and adults, untreated sleep apnea has been linked to cardiovascular problems and learning and memory deficits. However, the cognitive effects of untreated apnea might be far more damaging in children than in adults, the researchers pointed out, because they occur during critical developmental periods. The frontal cortex matures throughout the teen years and well into the 30s, and the researchers feared that childhood injury to this area might lead to long-term cognitive deficits.
Obstructive sleep apnea affects 2% of children in the United States, but it is unclear how many of these suffer from severe apnea. Halbower estimated that up to 17% of sleep apnea patients seen at the Children Center’s sleep clinic have the severe form.
Leptin Not Cause of Obesity in Narcoleptics
The hormone leptin does not cause a person with narcolepsy to be overweight, according to a study published in the August 1 issue of the journal Sleep.
Isabelle Arnulf, MD, PhD, of the Center for Narcolepsy and the Department of Psychiatry and Behavioral Sciences at Stanford University in California, sought to understand why many narcoleptic patients are overweight. According to Arnulf, a person with narcolepsy lacks hypocretin—a neurotransmitter that wakes you up to find food when your food stores (eg, fat cells) are empty—and should sleep more and eat less, not gain weight.
Arnulf checked the leptin levels in more than 100 narcoleptic patients, with and without central hypocretin deficiency, and in controls. She found that serum leptin levels for narcoleptic patients were normal.
A narcoleptic patient can also gain weight because, despite their fat cells being full and having sent a high leptin signal to the brain, the signal did not properly cross the blood-brain barrier, Arnulf theorized. “Therefore, the brain is not informed of full stores, and does not stop appetite systems,” she said. “We checked that, too, measuring leptin levels in the cerebro-spinal fluid, and which ratio crossed correctly from the blood to the brain. And that was normal, too, in narcolepsy.”
In animal models, leptin blocks hypocretin cells, so that once a person has had enough to eat, he or she can stop eating and sleep, Arnulf said, adding that, in patients and healthy subjects with normal hypocretin cells, higher cerebrospinal fluid (CSF) leptin levels tended to correlate with higher (not lower, as expected) CSF hypocretin levels. As a result, the relationship between leptin and hypocretin may be different in humans than in animals, she noted.
Study Shows New Drug Helps Elderly With Insomnia
The drug eszopiclone, marketed as Lunesta, significantly improved sleep in elderly people with chronic insomnia, according to a report by W. Vaughn McCall, MD, MS, and six colleagues.
“Eszopiclone was well tolerated and significantly improved sleep onset, sleep efficiency, total sleep time, and sleep quality over the study period,” said McCall, director of the sleep laboratory at Wake Forest University Baptist Medical Center in Winston-Salem, NC, and professor and chairman of the Department of Psychiatry and Behavioral Medicine, in the study published in Current Medical Research and Opinion.
He said eszopiclone significantly reduced wakefulness after sleep had begun, wake time during the sleep period, and daytime napping.
McCall said that daytime napping was more common in elderly patients with insomnia than in good sleepers and that napping increases with age. “The finding of less daytime napping associated with eszopiclone treatment in the present study could be interpreted as evidence of improvement in some aspects of daytime function in these elderly insomniacs.”
The study compared eszopiclone with an inert placebo in patients 64 to 86 years old over a 2-week period and used both measurements made in sleep laboratories and patients’ own reports of their sleep activity during the study.
The 136 patients in the eszopiclone group reported greater quality of sleep and greater depth of sleep than the 128 patients in the control group, he said. “Upon awakening, patients treated with eszopiclone reported less morning sleepiness compared with placebo.”
Since patients were in the study for only 2 weeks, McCall said longer-term studies are needed to determine the safety of longer treatment. Sepracor Inc, makers of Lunesta, paid for the study as part of a new drug submission to the US Food and Drug Administration (FDA). McCall also has been an advisor to Sepracor.
SR Poll: Patients Shouldn’t Have to Report OSA to DMV
In July, a New York teenager was killed by a driver who fell asleep at the wheel. The driver had been diagnosed with sleep apnea, but was not complying with treatment. In an August Web poll, Sleep Review asked if people with sleep apnea should be required to report their condition to the department of motor vehicles and/or their car insurance agents. Nearly three quarters of readers said no. To register your opinions on issues in sleep medicine, please visit us online at www.sleepreviewmag.com.
Research Links Asthma to Increased Risk for Sleep Apnea in Young Women
Researchers from the University of Cincinnati (UC) and Cincinnati Children’s Hospital Medical Center (CCHMC) have found that young women with asthma are twice as likely to have symptoms of obstructive sleep apnea—a condition that often goes undetected in women—compared with those who do not have asthma.
The Cincinnati team found that about 21% of young adult women with asthma experienced habitual snoring, the primary symptom of obstructive sleep apnea.
These findings, the researchers said, disprove a long-held notion that obstructive sleep apnea predominantly affects males, and highlights the importance of identifying specific groups of women who are at high risk for the condition.
This study was reported in the August edition of the journal Annals of Allergy, Asthma and Immunology.
“For a long time, physicians believed that men were more likely than women to get obstructive sleep apnea, but we’ve shown that’s not necessarily true,” said Maninder Kalra, MD, lead author of the study and assistant professor of pediatrics at the UC College of Medicine. “Our study reinforces the need for awareness and early detection of the disease in women who are at increased risk for breathing disorders related to sleep.”
Left untreated, obstructive sleep apnea can lead to impaired memory, mood swings, restless sleep, and extreme daytime fatigue. Long-term effects can include higher blood pressure and decreased heart function.
“Physicians need to know the risk factors that predispose a patient to obstructive sleep apnea,” Kalra added, “so we can get those patients in for a conclusive test—such as a sleep study—and start treatment sooner.”
The UC-led research team also found that women who smoked cigarettes were at a higher risk for snoring than those who did not smoke.
Researchers collected data from 677 mothers of infants enrolled in the UC environmental health department’s Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) about their history of snoring, respiratory symptoms, and cigarette smoking.
The CCAAPS, funded by the National Institute of Environmental Health Sciences, is a 5-year study examining the effects of environmental particulates on childhood respiratory health and allergy development. All families enrolled in the study had at least one confirmed allergy, in either the mother or the father. Environmental tobacco smoke exposure and any history of asthmatic conditions were measured by questionnaire. Researchers used this data to compare snorers with nonsnorers and determine risk factors for snoring in women under 50.
