REM sleep behavior disorder is a risk factor for Parkinson's disease

Patients suffering REM sleep behaviour disorders dream nightmares in which they are attacked and pursued, with the particularity that they express them by screaming, crying, punching and kicking while sleeping. Lancet Neurology has published the third consecutive work in five years about the relationship between this disorder and Parkinson's disease.

30 july 2011--The first work¹ showed in 2006 that 45% of patients who suffer this sleep disorder develop Parkinson's disease and other neurodegenerative diseases caused by a lack of dopamine in the brain. The second article² discovered that neuroimaging tests that measure dopamine in the brain, such as the brain SPECT, are useful to identify patients with REM sleep disorders with increased risk of developing a neurodegenerative diseases such as Parkinson's disease.

The new study applied brain SPECT to conclude that the levels of dopamine in the brain are quickly lowering over the years in patients with REM sleep behaviour disorder. This neuroimaging technique becomes the first tool to detect the disease progression at an early stage. The first author of the three articles is Dr. Àlex Iranzo, doctor from the Neurology Service at the Hospital Clínic of Barcelona, researcher at the Biomedical Research Institute of August Pi i Sunyer (IDIBAPS) and member of the Multidisciplinary Sleep Disorders Unit , and the senior authors were to Dr. Joan Santamaria and Dr. Eduard Tolosa, from the same institution.

The study involved comparing for three years the evolution of brain SPECT in 20 patients with REM disorder and 20 healthy controls. The neuroimaging technique measures the presence of dopamine in the substantia nigra, a part of the brain associated with learning and harmony of body movements. In Parkinson's disease a deficiency of dopamine in the substantia nigra causes tremor, stiffness and movement slowness in patients. Results show that after 3 years of monitoring the production of dopamine in the control group was reduced by 8% due to age, while the group of REM sleep disorder patients experienced a reduction of 20%. Once the 3 year follow-up ended, 3 of 20 patients in the REM sleep disorder group had developed Parkinson's disease and their dopamine reduction was around 30%.

The three works led by the IDIBAPS - Hospital Clínic of Barcelona team conclude that more efforts are needed to create neuroprotective drugs that prevent the progression from REM sleep behavior disorders to Parkinson's disease. For the first time scientists have a technique, brain SPECT, to evaluate whether these drugs are effective. Authors of the study suggest that,to be considered effective, a neuroprotective drug should significantly prevent the dopamine concentration from dropping in these patients.

More information: ¹ Lancet Neurol. 2006 Jul;5(7):552-3.² Lancet Neurol. 2010 Nov;9(11):1040-2.

Provided by IDIBAPS - Institut d'Investigacions Biomčdiques August Pi i Sunyer

Researchers develop light-treatment device to improve sleep quality in the elderly

Troy, N.Y.,30 may 2009 — Sleep disturbances increase as we age. Some studies report more than half of seniors 65 years of age or older suffer from chronic sleep disturbances. Researchers have long believed that the sleep disturbances common among the elderly often result from a disruption of the body's circadian rhythms—biological cycles that repeat approximately every 24 hours.

In recent years, scientists at Rensselaer Polytechnic Institute's Lighting Research Center and elsewhere have demonstrated that blue light is the most effective at stimulating the circadian system when combined with the appropriate light intensity, spatial distribution, timing, and duration. A team at the Lighting Research Center (LRC) has tested a goggle-like device designed to deliver blue light directly to the eyes to improve sleep quality in older adults.

"Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day," said Mariana Figueiro, Ph.D., Lighting Research Center Light and Health Program director and principal investigator on the project. "Light stimulus travels through the retina, the light-sensitive nerve tissue lining the back wall of the eye, to reach the master clock in the brain. However, a combination of age-related changes in the eye and a more sedentary lifestyle may reduce the amount of light stimulus reaching an older person's retina, therefore reducing the amount of light for the circadian system."

As we age, the lens in the eye thickens and the pupil shrinks, reducing the amount of light passing through to the retina. Making matters worse, in some cases, such as with persons with Alzheimer's disease, the circadian system may require a stronger light stimulus due to deteriorating neural processes in the brain. These physical and neural changes can lead to muted signals to the circadian system. Factor in environmental influences, such as an indoor lifestyle with less access to daylight, and you have a perfect scenario for the development of irregular sleep-activity patterns, according to Figueiro.

The research team explains that a marked increase in daytime lighting levels can counteract the age-dependent losses in retinal light exposure by providing a stronger signal to the circadian system. However, the color and intensity of commercially available lighting systems, like those used in senior residences, assisted-living facilities, and nursing homes, are designed for visual effectiveness and minimal energy use and not necessarily efficacious for generating light to stimulate the older circadian system.

Commercially-available "white" light sources advertised to treat circadian-related sleep disorders are usually very bright light and can cause glare and compromise compliance.

In this project, the light-treatment prototype tested by Figueiro's team was developed by Topbulb.com, LLC, based on prior LRC light and health research. The device offers an alternative approach using specially designed goggles that deliver blue light spectrally tuned for optimum circadian response.

"The goal of this phase of the development project was to create a device in a smaller form factor or envelope that allowed for social inclusion and end-user mobility, while still delivering the required dose of light," said Topbulb.com Senior Developer Philip H. Bonello, Ph.D.

The device was worn by eleven subjects between the ages of 51 and 80 years of age. Each subject was exposed to two levels of blue light (about 50 lux and 10 lux) from the personal light-treatment device for 90 minutes on two separate nights. Blood and saliva samples were collected at prescribed times to assess levels of nocturnal melatonin, a hormone used as a marker for the circadian clock, with high levels at night when a person is in a dark environment and low levels during the day.

After only one hour of light exposure, the light-induced nocturnal melatonin suppression level was about 35 percent for the low light level and about 60 percent for the high light level. In addition, the higher level of blue light suppressed nocturnal melatonin more quickly, to a greater extent over the course of the 90-minute exposure period, and was maintained after 60 minutes.

Having demonstrated its stimulation effect on the circadian system, the researchers believe the device could be subsequently used to increase sleep consolidation and efficiency in older subjects when worn for a prescribed duration at an appropriate time.

"The study suggests that the light goggles might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders. The next steps are to conduct field studies where we will be testing the effectiveness of this personal light-treatment device on those suffering from circadian-related sleep disorders, while also verifying the acceptance of the a device among the test groups," said Figueiro.

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Figueiro carried out her research with LRC scientists Andrew Bierman, John Bullough, Ph.D., and Mark Rea, Ph.D. They co-authored a paper detailing the study, "A Personal Light-Treatment Device for Improving Sleep Quality in the Elderly: Dynamics of Nocturnal Melatonin Suppression at Two Exposure Levels," which was recently published in Chronobiology International, Volume 26 Issue 4, 726.

This study was supported by the National Institute on Aging (1R41AG029693) through a Small Business Technology Transfer grant to Topbulb.com, LLC, a commercial and residential resource for light bulbs.

AGS: Stomach Upsets Sleep for Older Patients

SEATTLE, May 7 -- Sleep disturbances in older patients may signal gastroesophageal reflux, a panel of specialists said here.
Because aging dulls the classic daytime heartburn of gastroesophageal reflux disease (GERD), nighttime symptoms may herald continued "silent" damage, warned participants in an industry-sponsored satellite symposium held in conjunction with the American Geriatrics Society meeting.
Age-related physiologic changes increase older patients' risk from GERD, said James E. McGuigan, M.D., of the University of Florida in Gainesville.
For instance, peristalsis, which cleanses the esophagus of refluxed acid, progressively decreases with age, he said.
Medication plays a role, too. Some of the most common medications used by older patients are known to reduce lower esophageal pressure, Dr. McGuigan said. These include levodopa, opioid analgesics, and benzodiazepines.
Aging has also been associated with decreased sensory perception at striated muscle segments in the upper esophagus and at smooth muscle segments in the lower esophagus, Dr. McGuigan said. Thus, older patients have a longer lag time before sensation of esophageal pain in the presence of acid.
"If we have a situation in which we don't recognize sensation, we are less likely to do something about it pharmacologically," Dr. McGuigan said at the Wyeth-sponsored symposium.
"[GERD] is not less common because the disease is less severe," he said, "but because the sensation of pain -- heartburn -- is lessened in older patients."
The clinical presentation of GERD in older patients may be less typical than in younger patients, and more likely to include chest pain, vomiting, dysphagia, respiratory symptoms, and belching.
"Our index of suspicion has to be much higher than it would be otherwise," Dr. McGuigan said.
Older patients may also experience sleep disturbance as a symptom, said William C. Orr, Ph.D., a sleep expert at the Oklahoma University Health Sciences Center in Oklahoma City.
Three-quarters of adults with weekly GERD symptoms report nighttime heartburn, according to two epidemiologic studies that "turned the heads of a lot of gastroenterologists," Dr. Orr said.
Half of the patients in one study reported waking from sleep because of nocturnal symptoms; 40% of patients in the second study reported impaired functioning the next day.
During sleep, gravity impedes esophageal clearance and swallowing frequency drops, leading to prolonged acid contact time at night and changing the pattern of daytime symptoms, Dr. Orr said.
Previous studies have shown that nighttime reflux increases risk of GERD complications including erosive esophagitis, adenocarcinoma, asthma, and sleep deprivation.
"Acid mucosal contact during sleep will also produce arousals and sleep fragmentation," Dr. Orr said. "We've shown this time and time again in our laboratory."
In one of his laboratory experiments, exogenous infusion of acid into the esophagus while volunteers were asleep showed arousal from sleep both on electroencephalogram (EEG) and on submental electromyography (EMG).
A paper in press in the Journal of Clinical Sleep Medicine showed the same thing for 90% of spontaneous acid reflux events in patients, he said.
Older adults' attenuated esophageal sensory function could lead to longer reflux events and greater esophageal damage, Dr. Orr said. "It's adding insult to injury."
Sleep abnormalities could serve as "the needed clinical clue for identifying silent GERD," he said.
His 2005 study published in the American Journal of Gastroenterology indicated that 26% of older adults with no heartburn or other sleep disturbance actually had acid reflux during sleep.
Other studies have found so-called silent GERD in 6% to 23% of asymptomatic, healthy individuals screened using upper endoscopy.
Nighttime symptoms of GERD can be effectively treated with proton pump inhibitors (PPIs), said Denis M. McCarthy, M.D., Ph.D., of the University of New Mexico in Albuquerque.
In a small study in the American Journal of Gastroenterology in 2002, evening dosing of the PPI rabeprazole (Aciphex) reduced nighttime symptoms better than morning dosing.
It appears that PPIs have similar efficacy in daytime and nighttime symptoms, Dr. McCarthy said.
For patients who wake up at night with heartburn or have breakthrough symptoms, he suggested using an antacid rather than an H2 receptor antagonist, because these drugs inactivate PPIs.