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Biomedical subjects

David F Dinges

Publications and source records attributed to David F Dinges.

At least 19 recordsLinked to original sources

Consequences of comorbid insomnia symptoms and sleep-related breathing disorder in elderly subjects.

BACKGROUND: The prevalence of sleep-related breathing disorder (SRBD) and insomnia symptoms increases considerably with advancing age, but little is known about their cooccurrence and their effects on daytime functioning when present together. METHODS: Older adults with (cases, n = 99) and without (controls, n = 100) symptoms of insomnia underwent 2 nights of in-laboratory polysomnography, daytime nap, and neurobehavioral testing and completed study questionnaires. Predictors of SRBD were identified (apnea-hypopnea index [indicating number of events per hour], > or =15). Participants were divided into 4 groups--with and without insomnia and with and without SRBD--and the groups were compared on measures of daytime functioning. RESULTS: Cases had a lower rate of SRBD (29.3%) than controls (38.0%). Body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or higher, neck circumference greater than 15.5 inches, and a history of "loud snoring" or "stops breathing, chokes, or struggles for breath" were independently predictive of SRBD in participants with insomnia symptoms. Having both insomnia symptoms and SRBD was associated with significantly lower daytime functioning and longer psychomotor reaction times compared with having neither condition. CONCLUSION: Because insomnia comorbid with SRBD is associated with the greatest functional impairment, and SRBD is commonly found in the elderly population, health care providers should also consider SRBD in elderly patients with insomnia symptoms.

Aged↗

Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference.

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.

Adolescent↗

The neural basis of interindividual variability in inhibitory efficiency after sleep deprivation.

Sleep deprivation results in the loss of our ability to suppress a prepotent response. The extent of decline in this executive function varies across individuals. Here, we used functional magnetic resonance imaging to study the neural correlates of sleep deprivation-induced differences in inhibitory efficiency. Participants performed a go/no-go task after normal sleep and after 24 h of total sleep deprivation. Regardless of the extent of change in inhibitory efficiency, sleep deprivation lowered go/no-go sustained, task-related activation of the ventral and anterior prefrontal (PFC) regions bilaterally. However, individuals better able to maintain inhibitory efficiency after sleep deprivation could be distinguished by lower stop-related, phasic activation of the right ventral PFC during rested wakefulness. These persons also showed a larger rise in such activation both here and in the right insula after sleep deprivation relative to those whose inhibitory efficiency declined.

Adult↗

Impaired performance in commercial drivers: role of sleep apnea and short sleep duration.

Sleepiness plays an important role in major crashes of commercial vehicles. Because determinants are likely to include inadequate sleep and sleep apnea, we evaluated the role of short sleep durations over 1 wk at home and sleep apnea in subjective sleepiness (Epworth Sleepiness Scale), objective sleepiness (reduced sleep latency as determined by the Multiple Sleep Latency Test), and neurobehavioral functioning (lapses in performance, tracking error in Divided Attention Driving Task) in commercial drivers. Studies were conducted in 247 of 551 drivers at higher risk for apnea and in 159 of 778 drivers at lower risk. A multivariate linear association between the sets of outcomes and risk factors was confirmed (p < 0.0001). Increases in subjective sleepiness were associated with shorter sleep durations but not with increases in severity of apnea. Increases in objective sleepiness and performance lapses, as well as poorer lane tracking, were associated with shorter sleep durations. Associations with sleep apnea severity were not as robust and not strictly monotonic. A significant linear association with sleep apnea was demonstrated only for reduced sleep latency. The effects of severe apnea (apnea-hypopnea index, at least 30 episodes/h), which occurred in 4.7%, and of sleep duration less than 5 h/night, which occurred in 13.5%, were similar in terms of their impact on objective sleepiness. Thus, addressing impairment in commercial drivers requires addressing both insufficient sleep and sleep apnea, the former being more common.

Automobile Driving↗

Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: Correlations of fronto-parietal activation with performance.

Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep deprivation (SD) in 26 healthy young adults to examine the neural correlates of inter-individual differences in performance. The extent of performance decline was not significantly different between the two SD test periods although there was greater variability in performance at SD35. In both SD sessions, there was reduced task-related activation (relative to normal sleep) in both superior parietal regions and the left thalamus. Activation of the left parietal and left frontal regions after normal sleep was negatively correlated with performance accuracy decline from normal sleep to SD24 thus differentiating persons who maintained working memory performance following SD from those who were vulnerable to its effects.

Adult↗

Risk factors for excessive sleepiness in older adults.

OBJECTIVE: To determine risk factors for excessive daytime sleepiness in older adults. METHODS: This is a cross-sectional study assessing multiple risk factors for excessive daytime sleepiness in older subjects (mean age, 78 years; range 65-98 years) with (n=149) and without (n=144) complaints of frequent excessive daytime sleepiness. Assessment of risk factors included full in-laboratory sleep studies. RESULTS: Excessive sleepiness among the elderly is multifactorial. Multivariable modeling identified the following as simultaneously significant risk factors for excessive sleepiness: severe sleep-disordered breathing (apnea-hypopnea index, >30 episodes/hr), self-report of poor sleep quality, increased percentage of time in rapid eye movement sleep, pain at night at least three times per week, wheezing or whistling from chest at night, and medications with sleepiness as a side effect. Male sex also was associated with increased risk, whereas alcohol use (more than seven beverages per week) reduced the risk for sleepiness. Multiple risk factors were more commonly present in those with complaints of sleepiness. The presence of periodic limb movements, which are common in older adults, was not associated with sleepiness. INTERPRETATION: There is a distinct differential diagnosis of excessive daytime sleepiness in older adults. Many of the risk factors that we identified are treatable.

Aged↗

Sleepiness and relationships in obstructive sleep apnea.

This is a qualitative analysis of data from a multisite study of 156 participants with Obstructive Sleep Apnea (OSA). Participants completed a battery of tests, including the Functional Outcomes of Sleep Questionnaire (FOSQ) that contains an item assessing the impact of OSA on relationships. Approximately one third of participants wrote comments; they were predominately male, mean age 44.7, with severe OSA. Interpersonal themes expressed included work and marital problems and social life restriction. Intrapersonal themes included embarrassment and poor mood. This report adds specific details to previous reports of impaired relationships in OSA, and stresses the importance of assessing this critical area.

Conflict, Psychological↗

Assessment of sleep in women with night eating syndrome.

STUDY OBJECTIVES: Evaluation of sleep in subjects with night eating syndrome (NES). DESIGN: Polysomnographic and questionnaire comparisons between subjects with NES and controls. SETTING AND PARTICIPANTS: Fifteen women with NES (mean +/- SD = 41 +/- 8 years) and 14 women (comparable age and weight) without NES (39 +/- 10 years) were studied in the laboratory for 3 days. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Subjects with NES did not differ from controls in timing of sleep onset or offset. They had less stage 2 sleep than controls (minutes, p = .012; percentage, p = .016) and less stage 3 sleep (p = .023), which contributed to their having a lower total sleep time (p = .05) and reduced sleep efficiency (p = .03). Subjects with NES did not have more awakenings than controls, but 93.3% of them ate on awakening during all 3 nights, while 92.9% of controls did not eat on any night. Logistic discriminant analyses identified a multiple sleep parameter model associated with increased likelihood of NES that had sensitivity of 84.6% and specificity of 76.9%. Patients with NES were more depressed than controls (p < .001) and reported greater sleep disturbance that included lower sleep quality (p < or = .001), reduced sleep duration (p < or = .001), and increased number of awakenings (p < or = .001). CONCLUSIONS: Patients with NES appear to have sleep maintenance insomnia rather than sleep-related eating disorder or a parasomnia. The maintenance of normal timing for sleep-wake behavior in the presence of a phase delay in the timing of caloric intake suggests this disorder reflects a state of internal circadian desynchrony associated with significant sleep complaints. It remains unknown whether the sleep disturbance precedes the abnormally timed eating.

Adult↗

Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss.

OBJECTIVE: To assess the pharmacodynamics of armodafinil compared with modafinil and placebo on measures of alertness in healthy volunteers undergoing sleep loss. RESEARCH DESIGN AND METHODS: In a double-blind, active- and placebo-controlled, parallel-group study, 107 healthy male volunteers (aged 18-40 years) were randomized to receive a single oral dose of armodafinil (100, 150, 200, or 300 mg), modafinil (200 mg), or placebo administered at 19:25 h. MAIN OUTCOME MEASURES: The primary outcome was the Maintenance of Wakefulness Test (MWT), administered every 2 hours from 22:00-08:00 h. Secondary outcomes included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale. Blood samples for pharmacokinetic analysis were collected hourly. Adverse events were evaluated throughout the 2-day laboratory stay and by telephone on day 9. RESULTS: All four doses of armodafinil, and the dose of 200 mg modafinil, improved wakefulness as measured by increased MWT latencies (treatment effect, p < 0.0001) and reduced PVT lapses of attention (treatment effect, p < 0.0001). The magnitude and duration of these effects at the later time points appeared to be dose and concentration dependent. Armodafinil at 200 mg resulted in comparable C(max), a later t(max), and higher plasma concentrations 6-14 hours post-drug administration than with 200 mg modafinil. Following armodafinil, longer MWT latencies and fewer PVT lapses 6 to approximately 14 hours post-drug administration were observed compared with modafinil. Armodafinil doses were well tolerated, with the most common adverse events including abdominal pain, nausea, and headache. There were reports of tachycardia/palpitations. Decreased mean sleep efficiency and increased mean blood pressure were also observed. CONCLUSION: Armodafinil improved alertness at all doses studied. Relative to modafinil 200 mg, armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6-14 hours post-drug, and improved wakefulness and sustained attention for a longer time post-dose. Both drugs were well tolerated; however, further research on the efficacy, safety, and tolerability of armodafinil in patients with disorders of excessive sleepiness (ES) is required.

Adolescent↗

Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress.

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response.

Adult↗

Neuroendocrine profiles associated with energy intake, sleep, and stress in the night eating syndrome.

CONTEXT: Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings with ingestion of food. It is associated with obesity and depressed mood. Greater understanding of hormonal influences on NES is desirable. OBJECTIVE: Our objective was to evaluate 25-h profiles of hormones involved in energy balance, sleep, and stress in NES. DESIGN: Blood assays for glucose, insulin, ghrelin, leptin, melatonin, cortisol, TSH, and prolactin were sampled repeatedly among NES and control subjects. Food intake and depressive symptoms were assessed. SETTING AND PARTICIPANTS: Fifteen NES and 14 matched control participants stayed three nights in a General Clinical Research Center. MAIN OUTCOME MEASURES: We assessed differences between NES and control participants in the 25-h profiles of eight hormones. RESULTS: Nocturnal food intake was higher among NES participants, although their daily calorie intake was similar to that of controls. Reflecting their increased nocturnal intake, insulin (P < 0.001) and glucose levels (P = 0.07) among NES participants were higher than those of controls. Ghrelin levels were significantly lower in NES participants than in controls from 0100-0900 h (P = 0.003). Levels of plasma cortisol, melatonin, leptin, and prolactin did not differ between groups, but there was a trend for TSH levels (P = 0.07) to be higher during the 25 h in NES. NES participants had greater depressive symptoms than controls (P < 0.001). The differences in the levels of glucose, insulin, and ghrelin between NES and controls are closely associated with nocturnal food intake.

Adult↗

Modafinil for excessive sleepiness associated with shift-work sleep disorder.

BACKGROUND: Patients with shift-work sleep disorder chronically have excessive sleepiness during night work and insomnia when attempting to sleep during the day. We evaluated the use of modafinil for treating sleepiness in patients with this disorder. METHODS: In a three-month, double-blind trial, we randomly assigned 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Assessments were performed with the use of the nighttime Multiple Sleep Latency Test, the Clinical Global Impression of Change, the Psychomotor Vigilance Test, diaries of patients, and daytime polysomnography. After randomization, we conducted monthly assessments. RESULTS: Treatment with modafinil, as compared with placebo, resulted in a modest improvement from baseline in mean (+/-SEM) nighttime sleep latency (the interval between the time a person attempts to fall asleep and the onset of sleep) (1.7+/-0.4 vs. 0.3+/-0.3 minutes, respectively; P=0.002), and more patients had improvement in their clinical symptoms (74 percent vs. 36 percent, respectively; P<0.001). Patients who were receiving modafinil also had a reduction in the frequency and duration of lapses of attention during nighttime testing of their performance on the Psychomotor Vigilance Test (change from baseline, a reduction in lapse frequency of 2.6 vs. an increase of 3.8, respectively; P<0.001), and proportionally fewer patients reported having had accidents or near accidents while commuting home (29 percent vs. 54 percent, respectively; P<0.001). Despite these benefits, patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. Modafinil did not adversely affect daytime sleep as compared with placebo. Headache was the most common adverse event. CONCLUSIONS: Treatment with 200 mg of modafinil reduced the extreme sleepiness that we observed in patients with shift-work sleep disorder and resulted in a small but significant improvement in performance as compared with placebo. However, the residual sleepiness that was observed in the treated patients underscores the need for the development of interventions that are even more effective.

Adult↗

Sleep, circadian rhythms, and psychomotor vigilance.

Psychomotor vigilance performance is highly relevant to athletic performance. It is influenced by a sleep homeostatic process, which builds up pressure for sleep during wakefulness and dissipates this pressure during sleep, and a circadian rhythm process, which produces a waxing and waning of pressure for wakefulness over a 24 hours of the day. During total sleep deprivation, these two processes cause performance to deteriorate progressively over days, modulated within days by further performance reductions at night and relative improvements during the daytime. As the homeostatic pressure for sleep builds up higher across prolonged wakefulness, the rate of dissipation of that pressure during subsequent sleep is enhanced exponentially, so that even brief periods of sleep provide significant performance recuperation. Nevertheless, sleep restriction practiced on a chronic basis induces cumulative performance deficits of the same order of magnitude as observed during total sleep deprivation. There are also considerable individual differences in the degree of vulnerability to performance impairment from sleep loss, and these differences represent a trait.

Adult↗

Caffeine: implications for alertness in athletes.

Caffeine is one of the most widely consumed drugs in the world, taken socially and for its alertness- and performance-promoting actions. Extensive reports assert that caffeine increases alertness and cognitive performance levels and, when taken before exercise, demonstrates ergogenic properties. Caffeine ingestion has been associated with increased performance during endurance submaximal, and acute, high-intensity exercise. The exact mechanism of action for the performance effects of caffeine is unknown, although several physiologically and psychologically based theories exist as to how caffeine achieves increased performance capabilities. This paper outlines the known sites of caffeine activity in the body,and discusses these with respect to the effects of caffeine observed during performance assessments.

Analgesia↗

Neurocognitive consequences of sleep deprivation.

Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.

Cognition Disorders↗