Coffee effectively attenuates impaired attention in ADORA2A C/C-allele carriers during chronic sleep restriction

Many people consume coffee to attenuate increased sleepiness and impaired vigilance and attention due to insufficient sleep. We investigated in genetically caffeine sensitive individuals whether ‘real world’ coffee consumption during a simulated busy work week counteracts disabling consequences of chronically restricted sleep. We subjected homozygous C-allele carriers of ADORA2A (gene encoding adenosine A2A receptors) to 5 nights of only 5 h time-in-bed. We administered regular coffee (n = 12; 200 mg caffeine at breakfast and 100 mg caffeine after lunch) and decaffeinated coffee (n = 14) in double-blind fashion on all days following sleep restriction. At regular intervals 4 times each day, participants rated their sleepiness and performed the psychomotor vigilance test, the visual search task, and the visuo-spatial and letter n-back tasks. At bedtime, we quantified caffeine and the major caffeine metabolites paraxanthine, theobromine and theophylline in saliva. The 2 groups did not differ in age, body-mass-index, sex-ratio, chronotype and mood states. Subjective sleepiness increased in both groups across consecutive sleep restriction days and did not differ. By contrast, regular coffee counteracted the impact of repeated sleep loss on sustained and selective attention, as well as executive control when compared to decaffeinated coffee. The coffee induced benefits on different aspects of performance lasted for 4–5 days of insufficient sleep. All differences between the groups disappeared after the recovery night and the cessation of coffee administration. The data suggest that ‘real world’ coffee consumption can efficiently attenuate sleep restriction-induced impairments in vigilance and attention in genetically caffeine sensitive individuals

Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A 1 receptors

Trait-like differences in cognitive performance after sleep loss put some individuals more at risk than others, the basis of such disparities remaining largely unknown. Similarly, interindividual differences in impairment in response to alcohol intake have been observed. We tested whether performance impairments due to either acute or chronic sleep loss can be predicted by an individual’s vulnerability to acute alcohol intake. Also, we used positron emission tomography (PET) to test whether acute alcohol infusion results in an up-regulation of cerebral A1 adenosine receptors (A1ARs), similar to the changes previously observed following sleep deprivation. Sustained attention in the psychomotor vigilance task (PVT) was tested in 49 healthy volunteers (26 ± 5 SD years; 15 females) (i) under baseline conditions: (ii) after ethanol intake, and after either (iii) total sleep deprivation (TSD; 35 hours awake; n = 35) or (iv) partial sleep deprivation (PSD; four nights with 5 hours scheduled sleep; n = 14). Ethanol- versus placebo-induced changes in cerebral A1AR availability were measured in 10 healthy male volunteers (31 ± 9 years) with [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX) PET. Highly significant correlations between the performance impairments induced by ethanol and sleep deprivation were found for various PVT parameters, including mean speed (TSD, r = 0.62; PSD, r = 0.84). A1AR availability increased up to 26% in several brain regions with ethanol infusion. Our studies revealed individual trait characteristics for being either vulnerable or resilient to both alcohol and to sleep deprivation. Both interventions induce gradual increases in cerebral A1AR availability, pointing to a potential common molecular response mechanism

Impact of recovery sleep after sleep deprivation on cerebral A1 adenosine receptor density

Impact of recovery sleep after sleep deprivation on cerebral A1 adenosine receptor densityElmenhorst D1, Elmenhorst EM2, Kroll T1, Matusch A1 Aeschbach D2 and Bauer A1,3 1 Forschungszentrum Jülich, Institute of Neuroscience and Medicine 2, Jülich, Germany, 2 German Aerospace Center, Institute of aerospace medicine, Cologne Germany, 3 Heinrich Heine University Düsseldorf, Medical Faculty, Neurological Department, Düsseldorf, Germany Objectives: Sleep loss triggers a reaction of the homeostatic sleep regulatory system in which adenosine is believed to play a key role. The brain adenosine concentration increases during wakefulness thereby inducing sleepiness [1]. If wakefulness is extended by sleep deprivation, this increase is accompanied by an up-regulation of adenosine receptor density [2].Previously, we found in subjects deprived of sleep for 28 hours, an increase of the distribution volume (VT) of the highly selective A1 adenosine receptor (A1AR) radioligand 18F CPFPX in a region-specific pattern in several brain regions (maximum: orbitofrontal cortex 15.3%, p=0.014, n=12). Whereas there were no significant changes (1.5%) in a control group (n=10) with regular sleep between both scans [2].The objective of the current study was to investigate if an extension of the wake period to 58 hours leads to a further increase of A1AR densities and if subsequent recovery sleep restores baseline levels of receptor densities.Methods: 15 healthy male volunteers participated in a dynamic 18F CPFPX bolus/infusions-PET study with blood sampling and metabolite correction. Subjects were scanned after 58 hours of sustained wakefulness and after 14 hours of recovery sleep at the same time of day on consecutive days under identical conditions.Regional VT were determined by calculating the tissue to plasma ratio during the steady state phase.Results: The distribution volumes after sleep deprivation (e.g. VT=0.83, orbitofrontal cortex) were found to be significantly higher than after the recovery sleep condition in all (sub)cortical regions investigated (10-14%, p=0.001-0.008). Compared to the baseline group of the preceding experiment (VT=0.73, n=22) the receptor density after recovery sleep (VT=0.72) was not significantly different. Conclusions: This study demonstrates that a single night of recovery sleep returns the increased A1AR availability in the human brain after prolonged sleep deprivation back to the level of normal sleeping controls. These findings support the general hypothesis of an increase in synaptic strength during wakefulness and downscaling during normal sleep as a maintenance mechanism of synaptic functionality. Research support: References: [1] Porkka-Heiskanen et al. 1997 Science 276:1265–1268[2]Elmenhorst D et al. J Neuroscience 2007; 27(9):2410 –241

Impact of recovery sleep after sleep deprivation on cerebral A1 adenosine receptor density

Impact of recovery sleep after sleep deprivation on cerebral A1 adenosine receptor densityElmenhorst D1, Elmenhorst EM2, Kroll T1, Matusch A1 Aeschbach D2 and Bauer A1,3 1 Forschungszentrum Jülich, Institute of Neuroscience and Medicine 2, Jülich, Germany, 2 German Aerospace Center, Institute of aerospace medicine, Cologne Germany, 3 Heinrich Heine University Düsseldorf, Medical Faculty, Neurological Department, Düsseldorf, Germany Objectives: Sleep loss triggers a reaction of the homeostatic sleep regulatory system in which adenosine is believed to play a key role. The brain adenosine concentration increases during wakefulness thereby inducing sleepiness [1]. If wakefulness is extended by sleep deprivation, this increase is accompanied by an up-regulation of adenosine receptor density [2].Previously, we found in subjects deprived of sleep for 28 hours, an increase of the distribution volume (VT) of the highly selective A1 adenosine receptor (A1AR) radioligand 18F CPFPX in a region-specific pattern in several brain regions (maximum: orbitofrontal cortex 15.3%, p=0.014, n=12). Whereas there were no significant changes (1.5%) in a control group (n=10) with regular sleep between both scans [2].The objective of the current study was to investigate if an extension of the wake period to 58 hours leads to a further increase of A1AR densities and if subsequent recovery sleep restores baseline levels of receptor densities.Methods: 15 healthy male volunteers participated in a dynamic 18F CPFPX bolus/infusions-PET study with blood sampling and metabolite correction. Subjects were scanned after 58 hours of sustained wakefulness and after 14 hours of recovery sleep at the same time of day on consecutive days under identical conditions.Regional VT were determined by calculating the tissue to plasma ratio during the steady state phase.Results: The distribution volumes after sleep deprivation (e.g. VT=0.83, orbitofrontal cortex) were found to be significantly higher than after the recovery sleep condition in all (sub)cortical regions investigated (10-14%, p=0.001-0.008). Compared to the baseline group of the preceding experiment (VT=0.73, n=22) the receptor density after recovery sleep (VT=0.72) was not significantly different. Conclusions: This study demonstrates that a single night of recovery sleep returns the increased A1AR availability in the human brain after prolonged sleep deprivation back to the level of normal sleeping controls. These findings support the general hypothesis of an increase in synaptic strength during wakefulness and downscaling during normal sleep as a maintenance mechanism of synaptic functionality. Research support: References: [1] Porkka-Heiskanen et al. 1997 Science 276:1265–1268[2]Elmenhorst D et al. J Neuroscience 2007; 27(9):2410 –241