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

Abstract

Sleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimer's disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r²β*=0.06), and is predictive of greater longitudinal memory decline in a large subsample (p=0.032, r²β*=0.07, N=66). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.

Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study

“…Although the exact mechanism of sleep disturbance involved in cognitive impairment has not been fully determined. A growing number of studies have found that sleep disorders may lead to cognitive impairment and accelerate AD pathology, including increased Aβ deposition in the brain [42][43][44][45][46][47][48]. Our recent studies also showed that sleep deprivation induced peripheral Aβ transport dysfunction in young adults, and Aβ accumulation in the brain in rats [49,50].…”

Mapping Sleep’s Oscillatory Events as a Biomarker of Alzheimer’s Disease

“…Slow wave events were categorized as high versus low transition frequency in accordance with previously published methods 33,35 . The distance between the trough and peak of each slow wave was calculated and resultant halfwave was converted into a frequency value in Hertz.…”

“…While the dataset utilized for our analyses is significantly larger than prior studies of SW-SP coupling and Alzheimer's-related pathology 33,34 , limitations in sample size may obscure possible differences between groups in the number of identified oscillatory events and sleep stage metrics, particularly in comparisons with the Aβ+CI group.…”

“…Timing irregularities of SW and SP coupling have been correlated with amyloid 33 and tau 34 in positron emission tomography (PET) imaging studies. Further, subpopulations of SW and SP oscillatory events demonstrate unique properties, and distinct relationships exist within SW events defined by either high versus low transition frequencies in the context of aging 35 , amyloid positivity 33 , and cognitive processes 33,36 .…”

“…Timing irregularities of SW and SP coupling have been correlated with amyloid 33 and tau 34 in positron emission tomography (PET) imaging studies. Further, subpopulations of SW and SP oscillatory events demonstrate unique properties, and distinct relationships exist within SW events defined by either high versus low transition frequencies in the context of aging 35 , amyloid positivity 33 , and cognitive processes 33,36 . Theta burst events are detectable prior to the troughs of SWs 5,6,25,26,37 and play a role in normal sleep-dependent memory processing 37,38 , although their relationships to SW subpopulations, and their potential changes in aging and neurodegenerative processes, have yet to be formally assessed.…”