Archive for January, 2015

New Therapy May Reset Biological Clocks

Biological clocks and sleep schedules may be able to be reset through administration of glucocorticoids, opening up new therapeutic avenues for improving the synchronization of the body’s various biological clocks, according to a new study.

Physiological changes over the course of a day are regulated by a circadian system composed of a central clock located deep within the center of the brain and multiple clocks located in different parts of the body.

“These results lead us to believe that we may one day be able to use a combined therapy that targets the central clock (inverting work schedules, administering controlled light therapy) with a pharmacological treatment that targets the peripheral clocks to ensure that all clocks are adjusted,” said lead author Diane B. Boivin, MD, PhD, Professor in the Faculty of Medicine at McGill University and the Founder/Director of the Centre for Study and Treatment of Circadian Rhythms of the Douglas Mental Health University Institute in Montreal.

In previous studies, Dr. Boivin and her team showed that desynchronized circadian clocks disrupt the sleep, performance, and cardiac parameters of night-shift workers.

The researchers also showed that exposing workers to bright light at night or adjusting work schedules can improve the synchronization of the central biological clock to their atypical work schedule.

“A single therapy can’t address the disruptions that occur in all biological clocks,” stated Dr. Boivin.

“For example, when used incorrectly, light therapy can even aggravate the situation.”


Clock genes drive biological clocks, and these genes are active in all body organs.

Animal studies have shown that the central biological clock in the brain sends signals to the clocks in other organs.

Glucocorticoids appear to play a central role in transmitting these signals.

Glucocorticoids, such as cortisol and cortisone, are essential for the utilization of carbohydrate, fat and protein by the body and for normal response to stress.

This is the first study to demonstrate that glucocorticoids play this role in humans, the researchers stated.

They studied the rhythmic expression of clock genes in white blood cells of 16 healthy volunteers to see how the volunteers adjusted to glucocorticoids administered in the late afternoon.

The results show that 20 mg of hydrocortisone taken orally acutely increased gene expression in peripheral blood mononuclear cell (PBMC) peripheral clocks.

After 6 days of hydrocortisone administration, the phases of central markers were not affected; however, expression of 2 genes in PBMCs were shifted by about 9.5 to 11.5 hours.

This suggests that biological rhythms may play a role in controlling immune function in night-shift workers, the investigators stated.


The new research opens the door to innovative therapies that adjust circadian rhythms in inverted sleep schedules, combining synchronizing agents for the central and peripheral clocks.

This has possible applications for travelers, night-shift workers, patients who are experiencing sleep disorders and circadian rhythm disorders, and persons with various psychiatric disorders, they stated.

“At this stage, we are not recommending the use of glucocorticoids to adjust the rhythms of night-shift workers, as there could be medical risks,” Dr Boivin said.

The researchers published their results online December 12, 2014 in The FASEB Journal.

Sleep Apnea Risk Swells With Asthma

If you have asthma, you may be at increased risk for sleep apnea, too.

A new study assessed the relationship of asthma with obstructive sleep apnea (OSA) using laboratory-based sleep studies, and found that pre-existent asthma was a risk factor for the development of clinically relevant OSA in adults over a 4-year period.

What’s more, this association was stronger among those who had asthma longer, according to the authors, led by Mihaela Teodorescu, MD, MS, of the William S. Middleton Memorial Veteran’s Hospital and the University of Wisconsin School of Medicine and Public Health in Madison.

OSA is very common and becoming increasingly prevalent among adults with asthma.

It adversely affects health and leads to a higher risk of death.

Earlier studies had suggested an association between asthma and OSA.

This study examined the prospective relationship of asthma with OSA.


Dr Teodorescu and colleagues used data from the Wisconsin Sleep Cohort Study, a population-based prospective epidemiologic study that included randomly selected adult employees of state agencies, age 30 to 60 years, in 1988.

The patients were recruited to attend overnight sleep studies and fill out health-related questionnaires about every 4 years.

Eligible participants were identified as free of OSA at study entry by 2 baseline sleep studies.

Slightly more than one-quarter of the 81 participants with asthma experienced incident OSA over their first observed 4-year follow-up intervals.

This compared to 16% of the 466 participants without asthma.

With the use of all available 4-year intervals, including multiple 4-year interval observations per participant, those with asthma experienced 45 incident OSA cases during 167 4-year intervals (27%) and those without asthma experienced 160 incident OSA cases during 938 4-year intervals (17%).

The risk of new OSA was increased nearly 40% in participants with preexisting asthma compared with those without asthma after the investigators controlled for sex, age, and baseline and change in body mass index — all factors known to contribute to sleep apnea.

The researchers asked the participants, “Do you have feelings of excessive daytime sleepiness?” to help determine habitual sleepiness.

Asthma duration was related to both new OSA and new OSA with habitual sleepiness, defined as answering “often” (5 to 15 times a month) and “almost always” (more than 15 times a month).

“Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted,” the researchers stated.


If these results are confirmed in a larger study with more asthma cases, the finding would have important clinical relevance, they suggested.

Dr Teodorescu recommends that physicians “look for OSA symptoms among asthma patients.

The literature suggests that OSA worsens asthma.

Treatment for OSA improves asthma symptoms during the day and night, as well as quality of life and lung function measures.

If you identify and treat OSA, the hope is that asthma control will improve.”

The researchers published their results in the January 13 issue of JAMA.

Headache Imaging Can Spot Brain Tumors

Reducing imaging tests for patients with headaches runs the risk of missing or delaying the diagnosis of brain tumors, according to a new study.

“Patients with brain tumors may present with isolated headaches in the absence of other neurological symptoms and signs.

Early diagnosis of brain tumors allows prompt treatment before more severe symptoms, reduced performance status, and worsened outcomes,” stated the researchers, led by neurosurgeon Ammar H. Hawasli, MD, from Washington University School of Medicine, St Louis.

“As physicians grapple with the difficult conflict between evidence-based cost-cutting guidelines and individualized patient-tailored medicine, they must carefully balance the costs and benefits of discretionary services, such as neuroimaging for headaches.”

Despite recently published guidelines to limit neuroimaging for headache, there has been a progressive increase in neuroimaging for headaches in the United States.

In most cases, diagnosis of migraine and other types of headache can be made in the doctor’s office, without any special tests.

“Nonetheless, neuroimaging in the United States between 2007 and 2010 for migraines and headaches approached $1.2 billion,” the researchers stated.

“Medical providers have likely continued high use of neuroimaging for headaches because of concerns about potential missed diagnoses and medical errors, which would adversely affect patient outcomes and, in turn, affect malpractice liability,” they said.


The recent guidelines seek to reduce the use of neuroimaging for patients with headaches to limit the use of unnecessary and costly medical tests.

For example, the “Choosing Wisely” guidelines developed by the American College of Radiology and Consumer Reports include the recommendation, “Don’t do imaging for uncomplicated headaches.”

“Although the intentions are laudable, these guidelines are inconsistent with the neurosurgeon’s experience with patients with brain tumor,” the investigators stated.

“Specifically, patients with brain tumors may present with isolated headaches in the absence of other neurological symptoms and signs.”


The researchers presented their analysis of a series of 95 patients with a confirmed diagnosis of brain tumor.

Nearly half of the patients had a combination of symptoms, such as seizures, cognitive and speech dysfunction, and other neurological abnormalities.

However, about one-fourth of the patients had isolated headaches, no symptoms, or nonspecific symptoms.

In 11 patients, headache was the only symptom of brain tumor; 4 of these patients had new-onset headaches that would have qualified them for neuroimaging under recently proposed guidelines.

The other 7 patients had migraine or other types of headache and would not have been chosen for neuroimaging.

Depending on which set of recent recommendations had been followed, neuroimaging would have been delayed or never performed in 3% to 7% of patients who had brain tumors.

“We support careful and sensible use of neuroimaging in which physicians exercise excellent clinical judgment to reduce waste in the medical system,” the researchers concluded.

“Although we do not recommend routine screening for the general population, we do contend that a substantial number of patients with brain tumors will present with isolated headaches.”

The researchers published their results in the January 2015 issue of Neurosurgery.

Night Shifts Upset Sleep, Up Heart Death Risk

Night shift work not only disrupts sleep patterns but also increases the risk of cardiovascular disease (CVD) and lung cancer deaths, according to one of the largest prospective cohort studies worldwide with a high proportion of rotating night shift workers and long follow-up time.

“Women working rotating night shifts for more than 5 years have a modest increase in all-cause and CVD mortality.

Those working more than 15 years of rotating night shift work have a modest increase in lung cancer mortality.

These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity,” report researchers led by Eva S. Schernhammer, MD, DrPH, Associate Professor of Medicine, Harvard Medical School, and Associate Epidemiologist, Department of Medicine, Brigham and Women’s Hospital, Boston.

There is substantial biological evidence that night shift work enhances the development of CVD.

In 2007, the World Health Organization classified night shift work as a probable carcinogen because of circadian disruption.


Sleep and the circadian system play an important role in cardiovascular health and anti-tumor activity.

The circadian system and its prime marker, melatonin, are considered to have anti-tumor effects through multiple pathways — including antioxidant activity, anti-inflammatory effects, and immune enhancement — and they exhibit beneficial actions on cardiovascular health by enhancing endothelial function, maintaining metabolic homeostasis, and reducing inflammation, the researchers noted.

“Direct nocturnal light exposure suppresses melatonin production and resets the timing of the circadian clock,” they stated.

“In addition, sleep disruption may also accentuate the negative effects of night work on health.

Taken together, substantial biological evidence supports the role of night shift work in the development of poor health conditions, including cancer, CVD, and ultimately, mortality.”


Using data from the Nurses’ Health Study, the international team of researchers analyzed 22 years of follow-up of nearly 75,000 women.

Night shift information was collected in 1988.

Rotating shift work was defined as working at least 3 nights per month in addition to days or evenings in that month.

The investigators found that working rotating night shifts for more than 5 years is associated with an increase in all-cause and CVD mortality.

Mortality from all causes appeared to be 11% higher for women with 6 to 14 years or more than 15 years of rotating night shift work.

CVD mortality appeared to be 19% and 23% higher for those groups, respectively.

There was no association between rotating shift work and any cancer mortality, except for lung cancer in those who worked the night shift for 15 or more years (25% higher risk).

“A single occupation (nursing) provides more internal validity than a range of different occupational groups, where the association between shift work and disease outcomes could be confounded by occupational differences,” the researchers noted.

“To derive practical implications for shift workers and their health, the role of duration and intensity of rotating night shift work and the interplay of shift schedules with individual traits (eg, chronotype) warrant further exploration,” they added.

The researchers published their results in the January 5, 2014 issue of the American Journal of Preventive Medicine.

Poor Sleep May Add to Dementia

Older men with sleep disturbances appear more likely to have brain changes associated with dementia, according to a new study, adding to evidence that poor sleep may play a role in mental decline.

“These findings suggest that low blood oxygen levels and reduced slow wave sleep may contribute to the processes that lead to cognitive decline and dementia,” said lead author Rebecca P. Gelber, MD, DrPH, of the VA Pacific Islands Health Care System and the Pacific Health Research and Education Institute in Honolulu.

Dr. Gelber and colleagues conducted a prospective cohort study of 167 Japanese American men, mean age 84 years, in Honolulu who underwent at-home sleep studies in 1999–2000.

All of the men were monitored until they died an average of 6.4 years later.

Autopsies were conducted on their brains to look for microinfarcts (tiny abnormalities in brain tissue), loss of brain cells, the plaques and tangles associated with Alzheimer disease, and Lewy bodies found in Lewy body dementia.

Loss of brain cells was more common in men who spent less time in slow wave, or deep, sleep (sleep that is important in processing new memories and remembering facts) than in those who spent more time in slow wave sleep.

People tend to spend less time in slow wave sleep as they age, the researchers noted.

Loss of brain cells also is associated with Alzheimer disease and dementia.


The researchers divided the participants into 4 groups based on the percentage of time spent with lower than normal blood oxygen levels during sleep.

The lowest group spent 13% of their time or less with low oxygen levels, and the highest group spent 72% to 99% of the night with low oxygen levels.

Microinfarcts in the brain were seen almost 4 times as frequently in the one-fourth of men with the lowest oxygen levels during sleep than in men who had the highest oxygen levels.

There was no association between the sleep measures and the level of plaques and tangles.

The researchers noted that the causes of low oxygen levels during sleep were unclear and that brain changes could have occurred before the sleep tests.

Previous studies also have shown a link between sleep stages and dementia.

But this is the first study to show that certain sleep features are related to brain changes, Dr. Gelber noted.

“More research is needed to determine how slow wave sleep may play a restorative role in brain function and whether preventing low blood oxygen levels may reduce the risk of dementia,” she said.

Although the study did not actually show that sleep apnea per se is related to brain changes, Dr. Gelber noted that a previous study showed that use of a continuous positive airway pressure machine for obstructive sleep apnea may improve cognition, even after dementia has developed.

The researchers published their results on December 10, 2014 in the online issue of Neurology.