Timely sleep coupling: phase locked slow wave - spindle pairing is linked to AD neuropathology and forecasts cognitive decline

Alteration of sleep quality is a hallmark of the ageing process. The fine-tuned coalescence of elements of sleep microstructure seems to play a pivotal role in cognitive trajectories in ageing. This may be of prime clinical importance as a bidirectional detrimental relationship between sleep quality and Alzheimer’s disease (AD) neuropathology emerges in the literature and holds promise for novel sleep related interventions. However, sleep is not yet established as a true risk factor for AD, most likely because the understanding of its core associations with AD neuropathology remains insufficient. In this context, we focused on the timely coupling of two key graphoelements of Non-Rapid Eye Movement (NREM) sleep that is slow waves and spindles, and their associations with AD neuropathology and cognition.
We show, in a detailed large dataset (N=100; 68 woman) of undisturbed sleep recorded in late middle-aged healthy individuals (50 to 70y; 60 +- 5), that the precise coupling of sleep spindles with a specific category of sleep slow waves, those deemed most important for memory consolidation, is associated to lower medial prefrontal cortex PET-scan β-Amyloid burden, a landmark of AD neuropathology (F1,96=6.2, p=0.014). Cruder aspects of sleep macrostructure and sleep intensity were, however, not significantly linked to β-Amyloid burden in this relatively young sample with low β-Amyloid deposit. We further show that this specific coupling is predictive of a lower memory decline, assessed over 2 years using a task highly sensitive to the first signs of memory impairment (F1,54=4.67, p=0.035).
These findings unravel early links between sleep, AD-related and cognitive trajectories in ageing and suggest that altered coupling of sleep microstructure elements key to its functions could constitute the first association with AD neuropathology and that less refined measures of sleep macrostructure or sleep intensity may only be significantly associated to AD neuropathology later in life, when β-amyloid burden is higher. Sleep microstructure integrity could therefore constitute a potential indicator of a less successful ageing trajectory.