University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland
University Hospital of Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland.
J Neurosci. 2023 Sep 6;43(36):6268-6279. doi: 10.1523/JNEUROSCI.0586-23.2023. Epub 2023 Aug 16.
A well orchestrated coupling hierarchy of slow waves and spindles during slow-wave sleep supports memory consolidation. In old age, the duration of slow-wave sleep and the number of coupling events decrease. The coupling hierarchy deteriorates, predicting memory loss and brain atrophy. Here, we investigate the dynamics of this physiological change in slow wave-spindle coupling in a frontocentral electroencephalography position in a large sample ( = 340; 237 females, 103 males) spanning most of the human life span (age range, 15-83 years). We find that, instead of changing abruptly, spindles gradually shift from being driven by slow waves to driving slow waves with age, reversing the coupling hierarchy typically seen in younger brains. Reversal was stronger the lower the slow-wave frequency, and starts around midlife (age range, ∼40-48 years), with an established reversed hierarchy between 56 and 83 years of age. Notably, coupling strength remains unaffected by age. In older adults, deteriorating slow wave-spindle coupling, measured using the phase slope index (PSI) and the number of coupling events, is associated with blood plasma glial fibrillary acidic protein levels, a marker for astrocyte activation. Data-driven models suggest that decreased sleep time and higher age lead to fewer coupling events, paralleled by increased astrocyte activation. Counterintuitively, astrocyte activation is associated with a backshift of the coupling hierarchy (PSI) toward a "younger" status along with increased coupling occurrence and strength, potentially suggesting compensatory processes. As the changes in coupling hierarchy occur gradually starting at midlife, we suggest there exists a sizable window of opportunity for early interventions to counteract undesirable trajectories associated with neurodegeneration. Evidence accumulates that sleep disturbances and cognitive decline are bidirectionally and causally linked, forming a vicious cycle. Improving sleep quality could break this cycle. One marker for sleep quality is a clear hierarchical structure of sleep oscillations. Previous studies showed that sleep oscillations decouple in old age. Here, we show that, rather, the hierarchical structure gradually shifts across the human life span and reverses in old age, while coupling strength remains unchanged. This shift is associated with markers for astrocyte activation in old age. The shifting hierarchy resembles brain maturation, plateau, and wear processes. This study furthers our comprehension of this important neurophysiological process and its dynamic evolution across the human life span.
在慢波睡眠期间，慢波和纺锤波的精心协调偶联支持记忆巩固。随着年龄的增长，慢波睡眠的持续时间和偶联事件的数量减少。偶联层次结构恶化，预示着记忆丧失和大脑萎缩。在这里，我们在一个大样本（= 340；237 名女性，103 名男性）中研究了在额中央脑电图位置的慢波-纺锤波偶联中这种生理变化的动力学，该样本跨越了人类生命的大部分范围（年龄范围，15-83 岁）。我们发现，纺锤波逐渐从被慢波驱动转变为随着年龄的增长而驱动慢波，而不是突然改变，从而逆转了通常在年轻大脑中看到的偶联层次结构。逆转程度与慢波频率越低有关，并且始于中年（年龄范围，约 40-48 岁），在 56 至 83 岁之间建立了一个反向层次结构。值得注意的是，耦合强度不受年龄影响。在老年人中，使用相位斜率指数（PSI）和偶联事件的数量测量的慢波-纺锤波偶联恶化与血浆神经胶质纤维酸性蛋白水平相关，该蛋白是星形胶质细胞激活的标志物。数据驱动的模型表明，睡眠时间减少和年龄增加导致偶联事件减少，同时星形胶质细胞激活增加。反直觉的是，星形胶质细胞激活与偶联层次结构的后移（PSI）相关联，朝着“年轻”状态发展，同时偶联发生和强度增加，这可能表明存在代偿过程。由于偶联层次结构的变化从中年开始逐渐发生，我们认为存在一个相当大的机会窗口，可以进行早期干预以抵消与神经退行性变相关的不良轨迹。有证据表明，睡眠障碍和认知能力下降是双向的、因果相关的，形成了一个恶性循环。改善睡眠质量可能会打破这个循环。睡眠质量的一个标志是睡眠振荡的清晰层次结构。先前的研究表明，在老年时，睡眠振荡会脱耦。在这里，我们表明，相反，层次结构在整个人类生命周期中逐渐变化，并在老年时逆转，而耦合强度保持不变。这种转变与老年时星形胶质细胞激活的标志物有关。转移的层次结构类似于大脑成熟、稳定和磨损过程。这项研究进一步加深了我们对这一重要神经生理过程及其在人类生命周期中的动态演变的理解。
