A1 adenosine receptor availability under chronic sleep restriction and its association with cognitive performance

Abstract

Objectives/Introduction: Studies on acute sleep deprivation have linked the individual vulnerability to sleep-loss induced performance impairments to the cerebral adenosinergic regulation. Here we aimed at investigating the impact of chronic sleep restriction on this system. Methods: Thirty-six volunteers followed a protocol of 3 baseline nights (8 h time in bed, TIB), 5 experimental nights, and one recovery night (8 h TIB). The sleep restriction group (N=21) had 5 h TIB during experimental nights, while the control group (N=15) had 8 h TIB. We quantified A1 adenosine receptor (A1AR) availability with [18F]CPFPX positron emission tomography at experimental day 5 (ED5) and at the recovery day (REC). Median reaction time (median RT) and 10th percentile of reaction time (10P RT) in a 10-min Psychomotor Vigilance Task were analysed at baseline day 3 (BL3), ED5, and REC. We used mixed ANOVAs with Tukey adjusted post-hoc comparisons for analyses. We correlated the change in A1AR availability (ED5 minus REC) with the change in performance. Results: A1AR availability neither differed between the sleep restriction group and the well-rested control group (both at ED5 and REC), nor within the sleep restriction group comparing ED5 and REC (all p>0.35). In the sleep restriction group, performance was impaired at ED5 and REC in comparison to BL (p<0.02), and did not differ between ED5 and REC (p>0.7). However, the individual change in A1AR availability was correlated with the change in performance (Median RT: r=0.46, p=0.06; 10P RT: r=0.54, p=0.03) such that faster RTs at REC compared to ED5 were associated with increased A1AR availability and vice versa. Conclusions: Even though performance was impaired by sleep restriction and remained impaired after recovery, A1AR availability was unchanged by sleep restriction. This contrasts with findings from total sleep deprivation in which we found impaired performance and increased A1AR availability after 52 h of wakefulness that were both restored to rested levels after recovery sleep. The findings reveal fundamental differences in the mechanisms through which total and chronic sleep loss affect adenosinergic regulation and cognitive performance.