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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 (SW) is associated with early amyloid-β (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70 years; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation SW is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r²_β*=0.06) and is predictive of greater longitudinal memory decline in a large subsample (p=0.032, r²_β*=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.

SUBMITTER: Chylinski D

PROVIDER: S-EPMC9177143 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Chylinski Daphne D Van Egroo Maxime M Narbutas Justinas J Muto Vincenzo V Bahri Mohamed Ali MA Berthomier Christian C Salmon Eric E Bastin Christine C Phillips Christophe C Collette Fabienne F Maquet Pierre P Carrier Julie J Lina Jean-Marc JM Vandewalle Gilles G

eLife 20220531

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 (SW) is associated with early amyloid-β (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals i ...[more]

PMID: 35638265

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Project description:BackgroundStage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ.MethodsWe examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology.ResultsForty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level).ConclusionsThe possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.

Dataset Information

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

Publications

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

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