Summary Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance ...performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing-response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted.
Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in ...δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of δ-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (δ2) and another unrelated to time-spent-awake with slow, linear decay (δ1). Reanalysis of previously published datasets demonstrates that δ-band heterogeneity after sleep deprivation is also present in human subjects. Similar to sleep deprivation, silencing of centromedial thalamus neurons boosted subsequent δ2-waves, specifically. δ2-dynamics paralleled that of temperature, muscle tone, heart rate, and neuronal ON-/OFF-state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated.
Sleep is not the mere absence of wakefulness, but an active state which is finely regulated. The homeostatic facet of sleep–wake regulation is keeping track of changes in ‘sleep propensity’ (or ...‘sleep need’), which increases during wakefulness and decreases during sleep. Increased sleep propensity following extended prior wakefulness (sleep deprivation) is counteracted by prolonged sleep duration, but also by enhanced non-rapid-eye-movement (nonREM) sleep intensity as measured by electroencephalographic (EEG) slow-wave activity (SWA, power within ∼1–4Hz). This highly reliable regulatory feature of nonREM sleep may be the most important aspect of sleep in relation to its function. The neurochemical mechanisms underlying nonREM sleep homeostasis are poorly understood. Here we provide compelling and convergent evidence that adenosinergic neurotransmission plays a role in nonREM sleep homeostasis in humans. Specifically, a functional polymorphism in the adenosine metabolizing enzyme, adenosine deaminase, contributes to the high inter-individual variability in deep slow-wave sleep duration and intensity. Moreover, the adenosine receptor antagonist, caffeine, potently attenuates the EEG markers of nonREM sleep homeostasis during sleep, as well as during wakefulness. Finally, adenosinergic mechanisms modulate individual vulnerability to the detrimental effects of sleep deprivation on neurobehavioral performance, and EEG indices of disturbed sleep after caffeine consumption. While these convergent findings strongly support an important contribution of adenosine and adenosine receptors to nonREM sleep homeostasis, further research is needed to elucidate the underlying mechanisms that mediate the actions of adenosine on sleep and the sleep EEG.
Summary
For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. For ~100 years now, systematic research has been performed, first started by ...testing the effects of different dosages of caffeine on sleep and waking behaviour. About 70 years ago, adenosine itself entered the picture as a possible ligand of the receptors where caffeine hooks on as an antagonist to reduce sleepiness. Since the scientific demonstration that this is indeed the case, progress has been fast. Today, adenosine is widely accepted as an endogenous sleep‐regulatory substance. In this review, we discuss the current state of the science in model organisms and humans on the working mechanisms of adenosine and caffeine on sleep. We critically investigate the evidence for a direct involvement in sleep homeostatic mechanisms and whether the effects of caffeine on sleep differ between acute intake and chronic consumption. In addition, we review the more recent evidence that adenosine levels may also influence the functioning of the circadian clock and address the question of whether sleep homeostasis and the circadian clock may interact through adenosinergic signalling. In the final section, we discuss the perspectives of possible clinical applications of the accumulated knowledge over the last century that may improve sleep‐related disorders. We conclude our review by highlighting some open questions that need to be answered, to better understand how adenosine and caffeine exactly regulate and influence sleep.
Background
Multisensor fitness trackers offer the ability to longitudinally estimate sleep quality in a home environment with the potential to outperform traditional actigraphy. To benefit from these ...new tools for objectively assessing sleep for clinical and research purposes, multisensor wearable devices require careful validation against the gold standard of sleep polysomnography (PSG). Naturalistic studies favor validation.
Objective
This study aims to validate the Fitbit Charge 2 against portable home PSG in a shift-work population composed of 59 first responder police officers and paramedics undergoing shift work.
Methods
A reliable comparison between the two measurements was ensured through the data-driven alignment of a PSG and Fitbit time series that was recorded at night. Epoch-by-epoch analyses and Bland-Altman plots were used to assess sensitivity, specificity, accuracy, the Matthews correlation coefficient, bias, and limits of agreement.
Results
Sleep onset and offset, total sleep time, and the durations of rapid eye movement (REM) sleep and non–rapid-eye movement sleep stages N1+N2 and N3 displayed unbiased estimates with nonnegligible limits of agreement. In contrast, the proprietary Fitbit algorithm overestimated REM sleep latency by 29.4 minutes and wakefulness after sleep onset (WASO) by 37.1 minutes. Epoch-by-epoch analyses indicated better specificity than sensitivity, with higher accuracies for WASO (0.82) and REM sleep (0.86) than those for N1+N2 (0.55) and N3 (0.78) sleep. Fitbit heart rate (HR) displayed a small underestimation of 0.9 beats per minute (bpm) and a limited capability to capture sudden HR changes because of the lower time resolution compared to that of PSG. The underestimation was smaller in N2, N3, and REM sleep (0.6-0.7 bpm) than in N1 sleep (1.2 bpm) and wakefulness (1.9 bpm), indicating a state-specific bias. Finally, Fitbit suggested a distribution of all sleep episode durations that was different from that derived from PSG and showed nonbiological discontinuities, indicating the potential limitations of the staging algorithm.
Conclusions
We conclude that by following careful data processing processes, the Fitbit Charge 2 can provide reasonably accurate mean values of sleep and HR estimates in shift workers under naturalistic conditions. Nevertheless, the generally wide limits of agreement hamper the precision of quantifying individual sleep episodes. The value of this consumer-grade multisensor wearable in terms of tackling clinical and research questions could be enhanced with open-source algorithms, raw data access, and the ability to blind participants to their own sleep data.
Acute caffeine intake affects brain and cardiovascular physiology, yet the concentration-effect relationships on the electroencephalogram and cardiac autonomic activity during sleep are poorly ...understood. To tackle this question, we simultaneously quantified the plasma caffeine concentration with ultra-high-performance liquid chromatography, as well as the electroencephalogram, heart rate and high-frequency (0.15-0.4 Hz) spectral power in heart rate variability, representing parasympathetic activity, with standard polysomnography during undisturbed human sleep. Twenty-one healthy young men in randomized, double-blind, crossover fashion, ingested 160 mg caffeine or placebo in a delayed, pulsatile-release caffeine formula at their habitual bedtime, and initiated a 4-hr sleep opportunity 4.5 hr later. The mean caffeine levels during sleep exhibited high individual variability between 0.2 and 18.4 μmol L
. Across the first two non-rapid-eye-movement (NREM)-rapid-eye-movement sleep cycles, electroencephalogram delta (0.75-2.5 Hz) activity and heart rate were reliably modulated by waking and sleep states. Caffeine dose-dependently reduced delta activity and heart rate, and increased high-frequency heart rate variability in NREM sleep when compared with placebo. The average reduction in heart rate equalled 3.24 ± 0.77 beats per minute. Non-linear statistical models suggest that caffeine levels above ~7.4 μmol L
decreased electroencephalogram delta activity, whereas concentrations above ~4.3 μmol L
and ~ 4.9 μmol L
, respectively, reduced heart rate and increased high-frequency heart rate variability. These findings provide quantitative concentration-effect relationships of caffeine, electroencephalogram delta power and cardiac autonomic activity, and suggest increased parasympathetic activity during sleep after intake of caffeine.
Cerebrospinal fluid (CSF) flow through the brain parenchyma is facilitated by the astrocytic water channel aquaporin 4 (AQP4). Homeostatically regulated electroencephalographic (EEG) slow waves are a ...hallmark of deep non-rapid eye movement (NREM) sleep and have been implicated in the regulation of parenchymal CSF flow and brain clearance. The human AQP4 gene harbors several single nucleotide polymorphisms (SNPs) associated with AQP4 expression, brain-water homeostasis, and neurodegenerative diseases. To date, their role in sleep-wake regulation is unknown. To investigate whether functional variants in AQP4 modulate human sleep, nocturnal EEG recordings and cognitive performance were investigated in 123 healthy participants genotyped for a common eight-SNP AQP4-haplotype. We show that this AQP4-haplotype is associated with distinct modulations of NREM slow wave energy, strongest in early sleep and mirrored by changes in sleepiness and reaction times during extended wakefulness. The study provides the first human evidence for a link between AQP4, deep NREM sleep, and cognitive consequences of prolonged wakefulness.
Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when ...caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
Caffeine, the circadian clock, and sleep Landolt, Hans Peter
Science (American Association for the Advancement of Science),
09/2015, Letnik:
349, Številka:
6254
Journal Article
Recenzirano
Why is caffeine intake at bedtime a sleep disrupter?
Caffeine wakes people up but also disrupts the quality of sleep. A new study by Burke
et al.
(
1
) reveals that consuming caffeine in the ...evening—the equivalent of a double espresso—delays the human endogenous circadian clock by antagonizing receptors for the endogenous sleep factor adenosine in the brain (see the figure). Mistimed caffeine consumption may contribute to the growing incidence of sleep problems in society.
PDF
