Sleep 2014

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – Using the adult treatment threshold for serum ferritin to guide treatment in children with restless sleep may lead to inappropriate iron supplementation.

In both adults and children, iron deficiency has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin less than 50 mcg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40-50 mcg/L also has been used in pediatric studies.

For children, however, a far lower level of 20 mcg/L appears more appropriate, Alyson Connor reported at the annual meeting of the Associated Professional Sleep Societies.

"Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated" periodic limb movement index, Ms. Connor said. "While many children may benefit from iron supplementation for these disorders, this area is worthy of further study as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain."

Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor, and her colleagues conducted a review of 537 children aged 12 months to 18 years who were referred to the University of Michigan pediatric sleep clinic. In this cohort (mean age was 8.9 years; 62% were male), a median serum ferritin level of 23.6 mcg/L was linked with polysomnographic measures of periodic limb movement index (PLMI) per hour of total sleep time of 5 or more, while a median level of 30 mcg/L was linked with PLMI less than 5. About 26% of the subjects had a PLMI of 5 or more.

"There was a significant association between serum ferritin and periodic limb movement index such that, for every 10-mcg/L increase in serum ferritin, it decreased the odds of having an elevated PLMI by 11%," Ms. Connor said. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography had significantly increased odds of a PLMI of 5 or more. Only 19% of patients had a serum ferritin above 50 mcg/L, while 50% had below 30 mcg/L.

"The cutoff of 50 is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity," Ms. Connor said.

Studies are needed to assess the link between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery, she said.

MINNEAPOLIS – Using the adult treatment threshold for serum ferritin to guide treatment in children with restless sleep may lead to inappropriate iron supplementation.

In both adults and children, iron deficiency has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin less than 50 mcg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40-50 mcg/L also has been used in pediatric studies.

For children, however, a far lower level of 20 mcg/L appears more appropriate, Alyson Connor reported at the annual meeting of the Associated Professional Sleep Societies.

"Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated" periodic limb movement index, Ms. Connor said. "While many children may benefit from iron supplementation for these disorders, this area is worthy of further study as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain."

Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor, and her colleagues conducted a review of 537 children aged 12 months to 18 years who were referred to the University of Michigan pediatric sleep clinic. In this cohort (mean age was 8.9 years; 62% were male), a median serum ferritin level of 23.6 mcg/L was linked with polysomnographic measures of periodic limb movement index (PLMI) per hour of total sleep time of 5 or more, while a median level of 30 mcg/L was linked with PLMI less than 5. About 26% of the subjects had a PLMI of 5 or more.

"There was a significant association between serum ferritin and periodic limb movement index such that, for every 10-mcg/L increase in serum ferritin, it decreased the odds of having an elevated PLMI by 11%," Ms. Connor said. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography had significantly increased odds of a PLMI of 5 or more. Only 19% of patients had a serum ferritin above 50 mcg/L, while 50% had below 30 mcg/L.

"The cutoff of 50 is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity," Ms. Connor said.

Studies are needed to assess the link between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery, she said.

MINNEAPOLIS – Using the adult treatment threshold for serum ferritin to guide treatment in children with restless sleep may lead to inappropriate iron supplementation.

In both adults and children, iron deficiency has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin less than 50 mcg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40-50 mcg/L also has been used in pediatric studies.

For children, however, a far lower level of 20 mcg/L appears more appropriate, Alyson Connor reported at the annual meeting of the Associated Professional Sleep Societies.

"Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated" periodic limb movement index, Ms. Connor said. "While many children may benefit from iron supplementation for these disorders, this area is worthy of further study as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain."

Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor, and her colleagues conducted a review of 537 children aged 12 months to 18 years who were referred to the University of Michigan pediatric sleep clinic. In this cohort (mean age was 8.9 years; 62% were male), a median serum ferritin level of 23.6 mcg/L was linked with polysomnographic measures of periodic limb movement index (PLMI) per hour of total sleep time of 5 or more, while a median level of 30 mcg/L was linked with PLMI less than 5. About 26% of the subjects had a PLMI of 5 or more.

"There was a significant association between serum ferritin and periodic limb movement index such that, for every 10-mcg/L increase in serum ferritin, it decreased the odds of having an elevated PLMI by 11%," Ms. Connor said. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography had significantly increased odds of a PLMI of 5 or more. Only 19% of patients had a serum ferritin above 50 mcg/L, while 50% had below 30 mcg/L.

"The cutoff of 50 is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity," Ms. Connor said.

Studies are needed to assess the link between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery, she said.

MINNEAPOLIS – Caffeine therapy for apnea of prematurity did not prevent the development of persistent and significant obstructive apnea in children by the time they were 9 years old.

"Apnea of prematurity occurs in more than three-quarters of infants born at under 30 weeks’ gestation, and more than half of these apneas are actually obstructive in nature," Dr. Carole Marcus, director of the sleep center at Children’s Hospital of Philadelphia, said at the annual meeting of the Associated Professional Sleep Societies. "Caffeine is now the most commonly used drug [to treat apnea of prematurity] in the NICU in infants less than 32 weeks’ gestation," she said.

The long-term effects of caffeine on sleep in the developing brain are not well understood. It is not known whether neonatal caffeine administration has permanent adverse effects on sleep architecture and ventilatory control, perhaps increasing the risk of later sleep disorders such as insomnia and obstructive sleep apnea (OSA).

In the earlier CAP (Caffeine for Apnea of Prematurity) trial, 793 premature infants with birth weights of 500-1250 g were randomly assigned to caffeine or placebo until therapy for apnea of prematurity was no longer needed. Caffeine significantly improved the rate of survival without neurodevelopmental disability at 18-21 months in these babies versus placebo (N. Engl. J. Med. 2007;357:1893-902).

The subsequent axillary long-term CAP-S (Sleep) trial of 201 CAP subjects looked at whether neonatal caffeine administration resulted in later sleep abnormalities. The researchers assessed the ex-premature children aged 5-11 years (mean age, 9 years) via sleep questionnaires, actigraphy, and full ambulatory (home-based) polysomnography. The patients assessed in CAP-S were from Canada or Australia, with a high proportion of white patients, high maternal education, and high socioeconomic status, "which is relevant to our obstructive sleep apnea outcomes," noted Dr. Marcus.

No significant differences were noted in children who had received caffeine, compared with those who did not, in terms of subjective measures of sleep quality or quantity. Total recording time and total sleep time on polysomnography were somewhat longer in the caffeine arm, but there was no difference seen in sleep efficiency between groups (P = .91).

However, OSA (apnea-hypopnea index of more than two episodes per hour) was common in both groups (8.2% of the caffeine group and 11% of the placebo group; P = .22). In contrast, the prevalence of OSA in the general pediatric population is 1%-4%.

Also, 24% of the caffeine group and 29% of the placebo group had OSA on polysomnography and/or a history of adenoidectomy/tonsillectomy, again with no difference between groups (P = .35).

A large proportion of subjects in both arms had elevated periodic limb movements (17.5% in the caffeine group and 11% in the placebo groups; P = .27), a proportion that was markedly higher than was the normal prevalence in cases in which the child had more than five episodes of periodic limb movement per hour, which lies between 5% and 8%."This study further supports the use of caffeine for apnea of prematurity as it has been shown to have quite a number of beneficial effects and no long-term adverse effects," said Dr. Marcus. "Further study is needed on the mechanisms underlying the high prevalence of sleep disorders, both OSA and [periodic limb movement syndrome], in ex-preterm infants."

Dr. Marcus said there is a long-term behavioral and neurocognitive outcomes study ongoing on the CAP cohort, but they were unable to combine those results with the sleep study results because the data were collected too far apart.

MINNEAPOLIS – Caffeine therapy for apnea of prematurity did not prevent the development of persistent and significant obstructive apnea in children by the time they were 9 years old.

"Apnea of prematurity occurs in more than three-quarters of infants born at under 30 weeks’ gestation, and more than half of these apneas are actually obstructive in nature," Dr. Carole Marcus, director of the sleep center at Children’s Hospital of Philadelphia, said at the annual meeting of the Associated Professional Sleep Societies. "Caffeine is now the most commonly used drug [to treat apnea of prematurity] in the NICU in infants less than 32 weeks’ gestation," she said.

The long-term effects of caffeine on sleep in the developing brain are not well understood. It is not known whether neonatal caffeine administration has permanent adverse effects on sleep architecture and ventilatory control, perhaps increasing the risk of later sleep disorders such as insomnia and obstructive sleep apnea (OSA).

In the earlier CAP (Caffeine for Apnea of Prematurity) trial, 793 premature infants with birth weights of 500-1250 g were randomly assigned to caffeine or placebo until therapy for apnea of prematurity was no longer needed. Caffeine significantly improved the rate of survival without neurodevelopmental disability at 18-21 months in these babies versus placebo (N. Engl. J. Med. 2007;357:1893-902).

The subsequent axillary long-term CAP-S (Sleep) trial of 201 CAP subjects looked at whether neonatal caffeine administration resulted in later sleep abnormalities. The researchers assessed the ex-premature children aged 5-11 years (mean age, 9 years) via sleep questionnaires, actigraphy, and full ambulatory (home-based) polysomnography. The patients assessed in CAP-S were from Canada or Australia, with a high proportion of white patients, high maternal education, and high socioeconomic status, "which is relevant to our obstructive sleep apnea outcomes," noted Dr. Marcus.

No significant differences were noted in children who had received caffeine, compared with those who did not, in terms of subjective measures of sleep quality or quantity. Total recording time and total sleep time on polysomnography were somewhat longer in the caffeine arm, but there was no difference seen in sleep efficiency between groups (P = .91).

However, OSA (apnea-hypopnea index of more than two episodes per hour) was common in both groups (8.2% of the caffeine group and 11% of the placebo group; P = .22). In contrast, the prevalence of OSA in the general pediatric population is 1%-4%.

Also, 24% of the caffeine group and 29% of the placebo group had OSA on polysomnography and/or a history of adenoidectomy/tonsillectomy, again with no difference between groups (P = .35).

A large proportion of subjects in both arms had elevated periodic limb movements (17.5% in the caffeine group and 11% in the placebo groups; P = .27), a proportion that was markedly higher than was the normal prevalence in cases in which the child had more than five episodes of periodic limb movement per hour, which lies between 5% and 8%."This study further supports the use of caffeine for apnea of prematurity as it has been shown to have quite a number of beneficial effects and no long-term adverse effects," said Dr. Marcus. "Further study is needed on the mechanisms underlying the high prevalence of sleep disorders, both OSA and [periodic limb movement syndrome], in ex-preterm infants."

Dr. Marcus said there is a long-term behavioral and neurocognitive outcomes study ongoing on the CAP cohort, but they were unable to combine those results with the sleep study results because the data were collected too far apart.

MINNEAPOLIS – Caffeine therapy for apnea of prematurity did not prevent the development of persistent and significant obstructive apnea in children by the time they were 9 years old.

"Apnea of prematurity occurs in more than three-quarters of infants born at under 30 weeks’ gestation, and more than half of these apneas are actually obstructive in nature," Dr. Carole Marcus, director of the sleep center at Children’s Hospital of Philadelphia, said at the annual meeting of the Associated Professional Sleep Societies. "Caffeine is now the most commonly used drug [to treat apnea of prematurity] in the NICU in infants less than 32 weeks’ gestation," she said.

The long-term effects of caffeine on sleep in the developing brain are not well understood. It is not known whether neonatal caffeine administration has permanent adverse effects on sleep architecture and ventilatory control, perhaps increasing the risk of later sleep disorders such as insomnia and obstructive sleep apnea (OSA).

In the earlier CAP (Caffeine for Apnea of Prematurity) trial, 793 premature infants with birth weights of 500-1250 g were randomly assigned to caffeine or placebo until therapy for apnea of prematurity was no longer needed. Caffeine significantly improved the rate of survival without neurodevelopmental disability at 18-21 months in these babies versus placebo (N. Engl. J. Med. 2007;357:1893-902).

The subsequent axillary long-term CAP-S (Sleep) trial of 201 CAP subjects looked at whether neonatal caffeine administration resulted in later sleep abnormalities. The researchers assessed the ex-premature children aged 5-11 years (mean age, 9 years) via sleep questionnaires, actigraphy, and full ambulatory (home-based) polysomnography. The patients assessed in CAP-S were from Canada or Australia, with a high proportion of white patients, high maternal education, and high socioeconomic status, "which is relevant to our obstructive sleep apnea outcomes," noted Dr. Marcus.

No significant differences were noted in children who had received caffeine, compared with those who did not, in terms of subjective measures of sleep quality or quantity. Total recording time and total sleep time on polysomnography were somewhat longer in the caffeine arm, but there was no difference seen in sleep efficiency between groups (P = .91).

However, OSA (apnea-hypopnea index of more than two episodes per hour) was common in both groups (8.2% of the caffeine group and 11% of the placebo group; P = .22). In contrast, the prevalence of OSA in the general pediatric population is 1%-4%.

Also, 24% of the caffeine group and 29% of the placebo group had OSA on polysomnography and/or a history of adenoidectomy/tonsillectomy, again with no difference between groups (P = .35).

A large proportion of subjects in both arms had elevated periodic limb movements (17.5% in the caffeine group and 11% in the placebo groups; P = .27), a proportion that was markedly higher than was the normal prevalence in cases in which the child had more than five episodes of periodic limb movement per hour, which lies between 5% and 8%."This study further supports the use of caffeine for apnea of prematurity as it has been shown to have quite a number of beneficial effects and no long-term adverse effects," said Dr. Marcus. "Further study is needed on the mechanisms underlying the high prevalence of sleep disorders, both OSA and [periodic limb movement syndrome], in ex-preterm infants."

Dr. Marcus said there is a long-term behavioral and neurocognitive outcomes study ongoing on the CAP cohort, but they were unable to combine those results with the sleep study results because the data were collected too far apart.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – Teens who do not sleep enough may be at risk for gaining weight and increased insulin resistance.

That’s the conclusion of a small pilot study conducted by Dr. Dorit Koren and her colleagues at the University of Chicago.

Alicia Ault/Frontline Medical News

There is already considerable epidemiologic data that lack of sleep is a risk factor for obesity in children and young adults, said Dr. Koren who is with the departments of pediatrics and medicine in the pediatric endocrinology department at the University of Chicago.

There have been studies examining the risk of type 2 diabetes with sleep deprivation in adults, but there has been no population-based data in children examining the risk of type 2 diabetes in children and adolescents – and that’s important because they are not just small adults, she said.

Adolescents tend to be more insulin resistant because of the pubertal growth spurt, and they have a different sleep architecture than do adults, as they tend to be late to bed and late to rise, said Dr. Koren.

Previous studies looking at glucose homeostasis in adolescents have mostly looked at fasting rather than dynamic measures of glucose homeostasis and that is a limitation because fasting measures reflect primarily hepatic insulin sensitivity, she said. Most studies also were conducted in a sleep lab, which is not a natural environment.

She and her colleagues wanted to study adolescents at home and also gauge postprandial glucose metabolism. They enrolled 10 adolescents, aged 13-18 years. A total of 70% were black and 30% were non-Hispanic white. Just under half were male. They were mostly overweight, as measured by body mass index, although some were very lean, and some were very obese, said Dr. Koren.

The patients were first given an overnight polysomnogram, and then told to measure sleep at home through an actigraphy device, and sleep diaries. The actigraphy helped back up the diaries, which are known to be "remarkably inaccurate" among adolescents, said Dr. Koren. They kept track of their sleep for 2 weeks.

The teens then returned for a second visit to the clinic. The researchers analyzed the average bedtime and waking time, and then asked them to restrict their sleep by going to bed an hour later. After returning again, the new measures after sleep restriction were compared with the earlier measures.

There was a strong correlation between weight and sleep duration, with longer sleep associated with less weight. They also saw a trend toward a greater waist circumference in adolescents who slept less.

There was a significant negative association between sleep duration and the 90-minute oral glucose tolerance test, with a P = .036. Restricted sleep also led to greater insulin resistance as measured by the homeostasis model assessment of insulin resistance (P = .091), and the whole-body insulin sensitivity index (P = .091).

Dr. Koren and her colleagues also performed linear regression analyses, controlling for either waist circumference or weight. Sleep deprivation was still the most significant factor as measured on the 90-minute glucose tolerance test and by the whole-body insulin sensitivity index.

"The model suggests that these relationships between home sleep deprivation and insulin resistance or hyperglycemia are independent of obesity, generalized or central," said Dr. Koren.

She cited the example of a 15-year-old female subject, who was lean. Her sleep went from 8.7 hours at baseline to 7.9 hours with the restriction. Her glucose values did not change significantly between baseline and restriction, but her insulin levels were noticeably higher in the sleep-restricted state, said Dr. Koren. Those levels rose an hour into the 90-minute tolerance test, which suggests that she was insulin resistant and needed to secrete more insulin to maintain glycemia.

Dr. Koren and her colleagues hope to replicate the study in a larger cohort.

Dr. Koren reported no relevant financial conflicts.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – Teens who do not sleep enough may be at risk for gaining weight and increased insulin resistance.

That’s the conclusion of a small pilot study conducted by Dr. Dorit Koren and her colleagues at the University of Chicago.

Alicia Ault/Frontline Medical News

There is already considerable epidemiologic data that lack of sleep is a risk factor for obesity in children and young adults, said Dr. Koren who is with the departments of pediatrics and medicine in the pediatric endocrinology department at the University of Chicago.

There have been studies examining the risk of type 2 diabetes with sleep deprivation in adults, but there has been no population-based data in children examining the risk of type 2 diabetes in children and adolescents – and that’s important because they are not just small adults, she said.

Adolescents tend to be more insulin resistant because of the pubertal growth spurt, and they have a different sleep architecture than do adults, as they tend to be late to bed and late to rise, said Dr. Koren.

Previous studies looking at glucose homeostasis in adolescents have mostly looked at fasting rather than dynamic measures of glucose homeostasis and that is a limitation because fasting measures reflect primarily hepatic insulin sensitivity, she said. Most studies also were conducted in a sleep lab, which is not a natural environment.

She and her colleagues wanted to study adolescents at home and also gauge postprandial glucose metabolism. They enrolled 10 adolescents, aged 13-18 years. A total of 70% were black and 30% were non-Hispanic white. Just under half were male. They were mostly overweight, as measured by body mass index, although some were very lean, and some were very obese, said Dr. Koren.

The patients were first given an overnight polysomnogram, and then told to measure sleep at home through an actigraphy device, and sleep diaries. The actigraphy helped back up the diaries, which are known to be "remarkably inaccurate" among adolescents, said Dr. Koren. They kept track of their sleep for 2 weeks.

The teens then returned for a second visit to the clinic. The researchers analyzed the average bedtime and waking time, and then asked them to restrict their sleep by going to bed an hour later. After returning again, the new measures after sleep restriction were compared with the earlier measures.

There was a strong correlation between weight and sleep duration, with longer sleep associated with less weight. They also saw a trend toward a greater waist circumference in adolescents who slept less.

There was a significant negative association between sleep duration and the 90-minute oral glucose tolerance test, with a P = .036. Restricted sleep also led to greater insulin resistance as measured by the homeostasis model assessment of insulin resistance (P = .091), and the whole-body insulin sensitivity index (P = .091).

Dr. Koren and her colleagues also performed linear regression analyses, controlling for either waist circumference or weight. Sleep deprivation was still the most significant factor as measured on the 90-minute glucose tolerance test and by the whole-body insulin sensitivity index.

"The model suggests that these relationships between home sleep deprivation and insulin resistance or hyperglycemia are independent of obesity, generalized or central," said Dr. Koren.

She cited the example of a 15-year-old female subject, who was lean. Her sleep went from 8.7 hours at baseline to 7.9 hours with the restriction. Her glucose values did not change significantly between baseline and restriction, but her insulin levels were noticeably higher in the sleep-restricted state, said Dr. Koren. Those levels rose an hour into the 90-minute tolerance test, which suggests that she was insulin resistant and needed to secrete more insulin to maintain glycemia.

Dr. Koren and her colleagues hope to replicate the study in a larger cohort.

Dr. Koren reported no relevant financial conflicts.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – Teens who do not sleep enough may be at risk for gaining weight and increased insulin resistance.

That’s the conclusion of a small pilot study conducted by Dr. Dorit Koren and her colleagues at the University of Chicago.

Alicia Ault/Frontline Medical News

There is already considerable epidemiologic data that lack of sleep is a risk factor for obesity in children and young adults, said Dr. Koren who is with the departments of pediatrics and medicine in the pediatric endocrinology department at the University of Chicago.

There have been studies examining the risk of type 2 diabetes with sleep deprivation in adults, but there has been no population-based data in children examining the risk of type 2 diabetes in children and adolescents – and that’s important because they are not just small adults, she said.

Adolescents tend to be more insulin resistant because of the pubertal growth spurt, and they have a different sleep architecture than do adults, as they tend to be late to bed and late to rise, said Dr. Koren.

Previous studies looking at glucose homeostasis in adolescents have mostly looked at fasting rather than dynamic measures of glucose homeostasis and that is a limitation because fasting measures reflect primarily hepatic insulin sensitivity, she said. Most studies also were conducted in a sleep lab, which is not a natural environment.

She and her colleagues wanted to study adolescents at home and also gauge postprandial glucose metabolism. They enrolled 10 adolescents, aged 13-18 years. A total of 70% were black and 30% were non-Hispanic white. Just under half were male. They were mostly overweight, as measured by body mass index, although some were very lean, and some were very obese, said Dr. Koren.

The patients were first given an overnight polysomnogram, and then told to measure sleep at home through an actigraphy device, and sleep diaries. The actigraphy helped back up the diaries, which are known to be "remarkably inaccurate" among adolescents, said Dr. Koren. They kept track of their sleep for 2 weeks.

The teens then returned for a second visit to the clinic. The researchers analyzed the average bedtime and waking time, and then asked them to restrict their sleep by going to bed an hour later. After returning again, the new measures after sleep restriction were compared with the earlier measures.

There was a strong correlation between weight and sleep duration, with longer sleep associated with less weight. They also saw a trend toward a greater waist circumference in adolescents who slept less.

There was a significant negative association between sleep duration and the 90-minute oral glucose tolerance test, with a P = .036. Restricted sleep also led to greater insulin resistance as measured by the homeostasis model assessment of insulin resistance (P = .091), and the whole-body insulin sensitivity index (P = .091).

Dr. Koren and her colleagues also performed linear regression analyses, controlling for either waist circumference or weight. Sleep deprivation was still the most significant factor as measured on the 90-minute glucose tolerance test and by the whole-body insulin sensitivity index.

"The model suggests that these relationships between home sleep deprivation and insulin resistance or hyperglycemia are independent of obesity, generalized or central," said Dr. Koren.

She cited the example of a 15-year-old female subject, who was lean. Her sleep went from 8.7 hours at baseline to 7.9 hours with the restriction. Her glucose values did not change significantly between baseline and restriction, but her insulin levels were noticeably higher in the sleep-restricted state, said Dr. Koren. Those levels rose an hour into the 90-minute tolerance test, which suggests that she was insulin resistant and needed to secrete more insulin to maintain glycemia.

Dr. Koren and her colleagues hope to replicate the study in a larger cohort.

Dr. Koren reported no relevant financial conflicts.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – The American Academy of Sleep Medicine is pushing to have a simple sleep apnea questionnaire included in the initial Welcome to Medicare preventive care visit.

Including such a screening tool would help identify obstructive sleep apnea (OSA) when patients first join the Medicare program and thus improve the odds of diagnosing and treating the condition, said Dr. Timothy Morgenthaler, president of the AASM. Getting a handle on OSA could also reduce the potential that the beneficiary will develop related chronic conditions, and that will help Medicare curb expenditures, he said.

An estimated 20% of current Medicare beneficiaries have OSA. That number is expected to grow with the rising obesity rates, he said. Untreated OSA can increase the risk of hypertension, heart disease, type 2 diabetes, and stroke, said Dr. Morgenthaler, who is professor of medicine at the Mayo Clinic in Rochester, Minn.

The AASM has been lobbying Congress to include a validated OSA screen in the initial Medicare visit and found sponsors in Rep. Michael Burgess (R-Tex.) and Rep. Bobby Rush (D-Ill.). The two congressmen introduced a bill (H.R. 4695) that would do just that on May 21.

"This important legislation addresses the barriers that prevent new Medicare beneficiaries from receiving what we know to be required sleep apnea services," Dr. Morgenthaler said at the annual meeting of the Associated Professional Sleep Societies.

Rep. Erik Paulsen (R-Minn.), who recently signed on to the bill as a cosponsor, told AASM attendees that adding an OSA screen to the initial Medicare visit would help increase detection of disease, raise patient awareness, and "improve health care quality and reduce costs to the Medicare program," over the long term.

The AASM is asking its members to back the legislation and educate local lawmakers and patients through the group’s Seniors Sleep Campaign.

The association also wants to make it easier for board-certified sleep medicine specialists to care for Medicare patients from start to finish. Currently, antikickback laws prevent sleep specialists and sleep centers from directly providing therapeutic durable medical equipment to Medicare patients, said Dr. Morgenthaler.

The AASM has developed model language for an exception to that statute, which it hopes legislators or regulators will approve, he said. It would allow board-certified specialists to provide the continuum of care from start to finish, including durable medical equipment such as continuous positive airway pressure devices.

Eliminating the current fragmented system of care would eliminate waste, simplify the work flow, and improve the quality of care and reduce costs, said Dr. Morgenthaler.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – The American Academy of Sleep Medicine is pushing to have a simple sleep apnea questionnaire included in the initial Welcome to Medicare preventive care visit.

Including such a screening tool would help identify obstructive sleep apnea (OSA) when patients first join the Medicare program and thus improve the odds of diagnosing and treating the condition, said Dr. Timothy Morgenthaler, president of the AASM. Getting a handle on OSA could also reduce the potential that the beneficiary will develop related chronic conditions, and that will help Medicare curb expenditures, he said.

An estimated 20% of current Medicare beneficiaries have OSA. That number is expected to grow with the rising obesity rates, he said. Untreated OSA can increase the risk of hypertension, heart disease, type 2 diabetes, and stroke, said Dr. Morgenthaler, who is professor of medicine at the Mayo Clinic in Rochester, Minn.

The AASM has been lobbying Congress to include a validated OSA screen in the initial Medicare visit and found sponsors in Rep. Michael Burgess (R-Tex.) and Rep. Bobby Rush (D-Ill.). The two congressmen introduced a bill (H.R. 4695) that would do just that on May 21.

"This important legislation addresses the barriers that prevent new Medicare beneficiaries from receiving what we know to be required sleep apnea services," Dr. Morgenthaler said at the annual meeting of the Associated Professional Sleep Societies.

Rep. Erik Paulsen (R-Minn.), who recently signed on to the bill as a cosponsor, told AASM attendees that adding an OSA screen to the initial Medicare visit would help increase detection of disease, raise patient awareness, and "improve health care quality and reduce costs to the Medicare program," over the long term.

The AASM is asking its members to back the legislation and educate local lawmakers and patients through the group’s Seniors Sleep Campaign.

The association also wants to make it easier for board-certified sleep medicine specialists to care for Medicare patients from start to finish. Currently, antikickback laws prevent sleep specialists and sleep centers from directly providing therapeutic durable medical equipment to Medicare patients, said Dr. Morgenthaler.

The AASM has developed model language for an exception to that statute, which it hopes legislators or regulators will approve, he said. It would allow board-certified specialists to provide the continuum of care from start to finish, including durable medical equipment such as continuous positive airway pressure devices.

Eliminating the current fragmented system of care would eliminate waste, simplify the work flow, and improve the quality of care and reduce costs, said Dr. Morgenthaler.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – The American Academy of Sleep Medicine is pushing to have a simple sleep apnea questionnaire included in the initial Welcome to Medicare preventive care visit.

Including such a screening tool would help identify obstructive sleep apnea (OSA) when patients first join the Medicare program and thus improve the odds of diagnosing and treating the condition, said Dr. Timothy Morgenthaler, president of the AASM. Getting a handle on OSA could also reduce the potential that the beneficiary will develop related chronic conditions, and that will help Medicare curb expenditures, he said.

An estimated 20% of current Medicare beneficiaries have OSA. That number is expected to grow with the rising obesity rates, he said. Untreated OSA can increase the risk of hypertension, heart disease, type 2 diabetes, and stroke, said Dr. Morgenthaler, who is professor of medicine at the Mayo Clinic in Rochester, Minn.

The AASM has been lobbying Congress to include a validated OSA screen in the initial Medicare visit and found sponsors in Rep. Michael Burgess (R-Tex.) and Rep. Bobby Rush (D-Ill.). The two congressmen introduced a bill (H.R. 4695) that would do just that on May 21.

"This important legislation addresses the barriers that prevent new Medicare beneficiaries from receiving what we know to be required sleep apnea services," Dr. Morgenthaler said at the annual meeting of the Associated Professional Sleep Societies.

Rep. Erik Paulsen (R-Minn.), who recently signed on to the bill as a cosponsor, told AASM attendees that adding an OSA screen to the initial Medicare visit would help increase detection of disease, raise patient awareness, and "improve health care quality and reduce costs to the Medicare program," over the long term.

The AASM is asking its members to back the legislation and educate local lawmakers and patients through the group’s Seniors Sleep Campaign.

The association also wants to make it easier for board-certified sleep medicine specialists to care for Medicare patients from start to finish. Currently, antikickback laws prevent sleep specialists and sleep centers from directly providing therapeutic durable medical equipment to Medicare patients, said Dr. Morgenthaler.

The AASM has developed model language for an exception to that statute, which it hopes legislators or regulators will approve, he said. It would allow board-certified specialists to provide the continuum of care from start to finish, including durable medical equipment such as continuous positive airway pressure devices.

Eliminating the current fragmented system of care would eliminate waste, simplify the work flow, and improve the quality of care and reduce costs, said Dr. Morgenthaler.

aault@frontlinemedcom.com

On Twitter @aliciaault

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.