197 Vigilance and cognitive impairment in adults with OSAS

Abstract

Although the effects of infectious diseases on sleep and sleepiness have been known for thousands of years, it is only within the past 20 years that there has been a systematic study of changes on sleep following infection or microbial product-induced cytokine production, primarily in animals. In humans, the first few studies focused on the circadian pattern of the cytokines and showed that proinflammatory cytokines peak during nocturnal sleep. Since 1997, there has been a focus on the potential role of proinflammatory cytokines in sleep loss and sleep disorders, such as sleep apnea and narcolepsy. IL-6 and TNFa appear to be elevated in patients with sleep apnea and narcolepsy and have been postulated to be mediators of excessive daytime sleepiness and fatigue. Also, it has been shown that cytokines are elevated in obese vs. normal-weight subjects and contribute to their frequent complaints of sleepiness and fatigue. Cytokines are produced by fat tissue and more so by visceral fat, which may explain why obesity per se is an independent risk factor for excessive daytime sleepiness. In addition, it has been shown that cytokines are elevated in conditions that their primary pathogenetic mechanism is insulin resistance, i.e., women with PCOS, and that they contribute both to their sleep pathology (increased prevalence of sleep apnea and sleepiness) as well as to the underlying pathogenetic mechanism of obesity and insulin resistance. In healthy, normal-sleeping humans, cytokines are elevated after total or partial sleep loss, suggesting a role in the mediation of experimentally induced sleepiness also. Interestingly, interventions to reduce or neutralize cytokines in humans are associated with improved alertness and performance. For example, a mid-afternoon nap following sleep deprivation improved sleepiness and performance and decreased IL-6 peripheral levels. Also, the use of a TNFa antagonist in obese patients with sleep apnea was associated with a marked decrease in sleepiness and a significant though slight improvement of sleep apnea. These studies collectively suggest that proinflammatory cytokines play a key role in sleep pathology, i.e., sleep apnea, sleepiness, and in health problems frequently associated with sleep disorders/ sleep loss, i.e., cardiovascular events, obesity, and metabolic syndrome. Future research in this area may lead to novel and more effective treatments for disorders that plague a large percentage of the population.