Heterogeneity in the links between sleep arousals, amyloid-β, and cognition

Abstract

BACKGROUND Tight relationships between sleep quality, cognition, and amyloid-β (Aβ) accumulation, a hallmark of Alzheimer’s disease (AD) neuropathology, have been shown. Sleep arousals become more prevalent with aging and are considered to reflect poorer sleep quality. However, heterogeneity in arousals has been suggested while their associations with Aβ and cognition are not established. METHODS We recorded undisturbed night-time sleep with EEG in 101 healthy individuals aged 50–70 years, devoid of cognitive and sleep disorders. We classified spontaneous arousals according to their association with muscular tone increase (M+/M–) and sleep stage transition (T+/T–). We assessed cortical Aβ burden over earliest affected regions via PET imaging and assessed cognition via neuropsychological testing. RESULTS Arousal types differed in their oscillatory composition in θ (4–8 Hz) and β (16–30 Hz) EEG bands. Furthermore, T+M– arousals, interrupting sleep continuity, were positively linked to Aβ burden ( P = 0.0053, R² β * = 0.08). By contrast, more prevalent T–M+ arousals, upholding sleep continuity, were associated with lower Aβ burden ( P = 0.0003, R² β * = 0.13), and better cognition, particularly over the attentional domain ( P < 0.05, R² β * ≥ 0.04). CONCLUSION Contrasting with what is commonly accepted, we provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. This suggests that sleep arousals, and their coalescence with other brain oscillations during sleep, may actively contribute to the beneficial functions of sleep and constitute markers of favorable brain and cognitive health trajectories. TRIAL REGISTRATION EudraCT 2016-001436-35. FUNDING FRS-FNRS Belgium (FRSM 3.4516.11), Actions de Recherche Concertées Fédération Wallonie-Bruxelles (SLEEPDEM 17/27-09), ULiège, and European Regional Development Fund (Radiomed Project).

Timely coupling of sleep spindles and slow waves linked to early amyloid-β burden and predicts memory decline

“…This finding argues against the idea that these rougher measures of sleep disruption constitute the earliest manifestations of the association between sleep and AD-related processes and contrasts with previous reports in a smaller sample of individuals older (>70 years) than our sample. Altogether, these discrepancies reinforce the idea that the alteration in the microstructure of sleep, consisting in the coupling of the spindles onto a specific subpopulation of SWs, as reported here, but also in the occurrence of microarousals during sleep we previously reported based on the same sample ( Chylinski et al, 2021 ), shows a prior association with AD-related processes compared with the amount of slow brain oscillations generated during overnight sleep. The latter may only be significantly associated at a later age, when the pathophysiological changes are already more substantial.…”

“… BMI, alcohol consumption, anxiety, and depression scores as well as sleepiness levels of the sample can be found in Chylinski et al, 2021 . TST: total sleep time.…”

Timely sleep coupling: spindle-slow wave synchrony is linked to early amyloid-β burden and predicts memory decline

“…This finding argues against the idea that these rougher measures of sleep disruption constitute the earliest manifestations of the association between sleep and AD-related processes and contrasts with previous reports in a smaller sample of individuals older (> 70y) than our sample. Altogether, these discrepancies reinforce the idea that the alteration in the microstructure of sleep, consisting in the coupling of the spindles onto a specific subpopulation of SWs, as reported here, but also in the occurrence of micro-arousals during sleep we previously reported based on the same sample 41 , shows a prior association with AD-related processes compared with the amount of slow brain oscillations generated during overnight sleep. The latter may only be significantly associated at a later age, when the pathophysiological changes are already more substantial.…”

“…In addition, the coupling of spindles onto slow switcher SWs is predictive of the future change in memory performance. Sleep microstructure could therefore constitute a promising early marker of future cognitive and brain ageing trajectory 41 . We did not evaluate whether distinct links between the SW types and slow and fast spindles are observed.…”

“…101 healthy participants aged from 50 to 70 y (68 women; mean ± SD = 59.4 ± 5.3 y) were enrolled between 15 June 2016 and 2 October 2019 for a multi-modal cross-sectional study taking place at the GIGA-Cyclotron Research Centre/In Vivo Imaging of the University of Liège (Cognitive fitness in aging – COFITAGE – study) which has already led to several scientific publications [e.g. 41,43 ]. One participant was excluded from analyses due to lack of PET imaging data.…”