Catch Your Zzz's Before You Age

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Sleep is an obvious necessity. With it we are able to rest our tired brains, restore the vigor to our bodies, and prepare ourselves for the labors of the coming day. Sleep, although universally considered a blessing, is a mysterious thing. Many individuals have difficulty falling and staying asleep and this may often be the result of a serious underlying disorder. Dr. Kathy C. Richards, Assistant Dean of the Doctoral Division and Research Development at the School of Nursing at George Mason University, presented the research she is currently working on with numerous faculty from varying universities. The focus of her research involves making sense of the relationship between sleep and cognitive function (1).

Dr. Richards began by introducing a concept known as 'sundowning'. This psychological phenomenon, known to affect some dementia patients, results in periods of increased confusion and agitation when the sun goes down, and sometimes all through the night. Sundowning not only prevents these patients from sleeping well, but also makes them more likely to wander and is a common cause of caregiver burnout (2). Although the cause of this syndrome is still unknown, Dr. Richards makes a correlation between two sleep disorders (RLS and PLMD) and sundowning. She explained that these disorders may be considered precursors of sundowning, and that sundowning itself may be a form of relief for patients suffering from these disorders (1). 

Restless leg syndrome (RLS) (sometimes referred to as 'elvis legs') is a disorder in which there is an urge to move, accompanied by or caused by uncomfortable sensations in the legs. The urge to move or the unpleasant sensations begin or worsen during periods of rest or inactivity, often at sleep onset. Partial or complete relief symptoms is achieved by movement such as walking or stretching. RLS occurs in 10% of the general population. Another form of RLS,  known as secondary RLS, is associated with certain conditions that older people have (1). These conditions include renal failure, iron deficiency, diabetes mellitus, Parkinson's disease, neuropathy. The use of dopamine antagonists and antidepressants as form of treatment have been shown to aggravate the condition. Dr. Richards stressed the importance of understanding the pathophysiology of RLS. In people suffering from RLS, there is a dysfunction of dopamine cells in certain areas of the brain. Iron is a necessary cofactor in the brain for dopamine synthesis and in RLS patients, iron stores are abnormally low in the cerebrospinal fluid (1). Treatment of RLS includes iron replacement therapy, as well as the use of anticonvulsants and general lifestyle changes to improve symptoms. 

Periodic limb movement disorder (PLMD) is a condition that also occurs in approximately 80% of people suffering from RLS (3). While the movements of RLS are a voluntary response to uncomfortable feelings in limbs when the person is awake, the movements of PLMD occur when a person is asleep and are involuntary (4). This condition occurs more commonly in older adults. Treatment for PLMD is the same as with RLS patients. PLMD movements are characterized by rhythmic extensions of the big toe and dorsiflexions of the ankle with occasional flexions of the knee and hip. Dr. Richards went into further detail about how a diagnosis of PLMD is made. Polysomnography (PSG) (also known as sleep study) tests are used as a diagnostic tool. In a study conducted on nursing home patients, muscle tension was measured by use of electrodes. They found that short awakening results in greater muscle tension. Electrodes placed on legs also shows flexion of both feet during sleep in PLMD patients (1). 

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Dr. Richards and her team conducted a study to better understand sleep and behavioral disturbances in dementia. They hypothesized that nighttime behavioral disturbances may be associated with with obstructive sleep apnea syndrome (OSA) as well as with PLMD and RLS. The study was conducted on 60 patients with dementia residing at home. It consisted of 2 nights of PSG monitoring, and 3 nights of behavioral observations done every 5 minutes, using the Cohen-Mansfield Agitation Inventory (CMAI) for direct observation (of a 19 hour duration) to calculate the behavioral disturbance index. Patients were categorized as having probable RLS or no RLS by the diagnoses of two world experts (1). They made these diagnoses by examining different factors including the chief sleep complaint, RLS diagnostic interview per the caregiver, research assistant observations of RLS signs and symptoms, and finally, polysomnography data including apnea hypopnea index (AHI) and periodic limb movement index (PLMI). 

The results of the study were analyzed through different means including electroencephalography (EEG). EEG measures voltage change and in dementia patients, voltage change will be low and there will be slowing in the wave forms. The frequency and shape of EEG wave forms changes in people with cognitive impairment. The sleep stages of people with dementia are different. Dr. Richards and her team developed guidelines with which to score dementia patients' sleep reliably in order to determine whether they were asleep or awake, and what stage they were in. In this study, they found that 24% of dementia patients have probable RLS, while the remaining have no RLS. They also found that OSA was not a predictor of nighttime behavioral problems (1). The lower the apnea index (AHI) and the mini-mental state examination scores (MMSE), the more likely dementia patients were to have nighttime behavioral disturbances. Additionally, it was found that PLMD was a significant predictor of RLS and more nighttime behavioral disturbances. 

Dr. Richards concluded by briefly explaining the work that she is involved in currently.  Obstructive sleep apnea (OSA) is the most common form of sleep apnea and is caused by obstruction of the upper respiratory pathway. It is characterized by repeated cessation of breathing during sleep and results in a reduction of oxygen saturation in the blood. Cognitive effects of OSA include impairment in attention-vigiliance, memory, and executive functioning. Neuroimaging studies have shown evidence of hippocampal atrophy, reduced grey matter, and reduced cerebral blood flow in OSA patients. Mild cognitive impairment (MCI) is a form of memory impairment with little or no decline in everyday function. OSA is widely associated with increased risk of developing MCI or dementia. Dr. Richards and her team are currently exploring methods in which OSA can be treated and cognitive decline can be delayed. They are looking into the use of continuous positive airway pressure (CPAP) as a means of treatment and therapy (1).

CPAP therapy uses a machine to help a person with OSA breathe more easily during sleep.
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The research that Dr. Richards and her team are undertaking is vital in developing a better understanding of sleep disorders and how they are related to patients suffering from dementia. It lays the groundwork on which future research can build upon. The clinical approach that Dr. Richards has taken with respect to this topic of study is important in that it opens doors for exploration of other means by which sleep disorders can be treated. She mentioned the need for an effective RLS behavioral diagnostic tool and this can possibly be a next step in her research. Dr. Richards also pointed out that RLS is commonly seen in autistic children. Perhaps her efforts will allow for a bridge between translational sleep and research aging and neuropsychopharmacology. With collaborative efforts from these two fields of research, would it be possible to develop a single drug that targets these sleeping disorders? Would it be possible to maintain a balance in the dopaminergic, serotonergic, and cholinergic systems of these patients through the use of a single drug? Other non-pharmacological means may be explored such as lifestyle changes that would make a difference. Recent discoveries in science have come a long way and have greatly increased our understanding of sleep disorders and we are on the path towards breakthrough treatment. 

Sources:

1. Richards, Dr. Kathy. "Sleep: A Key to Healthy Aging", School of Nursing: Doctoral Division and Research Development. 8 November 2012. Seminar.
2. "Sundowning: Causes, Symptoms, and Treatment." WebMD. WebMD, n.d. Web. 11. Nov. 2012. <http://www.webmed.com/alzheimers/guide/sundowning-causes-symptoms-treatments>.
3. "Restless Legs Syndrome." Harvard Health Publications. Harvard Medical School, n.d. Web. 11 Nov. 2012. <http://www.health.harvard.edu/newsweek/Restless-legs-syndrome.htm>.
4. "Restless Legs Syndrome and Periodic Limb Movement Disorder." MetroHealth. Center For Sleep Medicine, n.d. Web. 11 Nov. 2012. <http://www.metrohealth.org/body.cfm?id=2080>.