Nenert Rodolphe, Mueller Christina, Catiul Corina, Pilkington Jennifer, LeVan Pierre, Sharma Ayushe, Szaflarski Jerzy P, Amara Amy W
University of Alabama at Birmingham (UAB) Heersink School of Medicine Departments of Neurology, USA.
University of Alabama at Birmingham (UAB) Heersink School of Medicine Departments of Neurology, USA.
Neuroimage. 2025 May 1;311:121187. doi: 10.1016/j.neuroimage.2025.121187. Epub 2025 Apr 3.
The glymphatic system facilitates efficient waste clearance in the brain through the movement of cerebrospinal fluid (CSF) along perivascular spaces. Animal studies have demonstrated that glymphatic efficiency declines with age, but evidence for such decline in humans is limited. We hypothesized that reduced glymphatic efficiency in older adults may be related to age-related worsening of sleep quality, potentially contributing to cognitive impairment.
20 participants aged ≥60 years provided multi-dimensional cognitive measures, overnight polysomnography, and Magnetic Resonance Encephalography (MREG) performed the morning following the PSG. MREG is a single-shot, three-dimensional (3D) sequence employing a spherical stack-of-spirals trajectory that undersamples 3D k-space, enabling whole-brain data acquisition every 100 milliseconds to non-invasively and dynamically assess brain physiological pulsations. Spectral power and optical flow analyses quantified physiological pulsations within cardiovascular (CvB; 0.52-1.6 Hz), respiratory (RFB; 0.11-0.44 Hz), and low-frequency (LFB; 0.008-0.1 Hz) bands. These measures were correlated with cognitive test scores and sleep parameters assessed by overnight polysomnography.
Significant associations emerged between physiological pulsations, sleep, and cognitive measures. Cardiovascular pulsation strength correlated with non-rapid eye movement (NREM) stage 3 (N3) sleep percentage (peak voxel in right frontal pole; r = 0.72, p < 0.001) and language domain performance (left calcarine gyrus; r = 0.56, p = 0.01). Respiratory pulsations correlated strongly with sleep onset latency (right inferior temporal gyrus; r = 0.75, p < 0.001). Additionally, low-frequency pulsations were associated with sleep onset latency (right precentral gyrus; r = 0.67, p = 0.002). These findings suggest that glymphatic efficiency, as reflected by brain pulsations, is closely linked to sleep quality and cognitive performance in older adults, particularly involving cortical and subcortical structures relevant to cognitive and sleep regulatory functions.
This study uniquely demonstrates that brain physiological pulsations measured non-invasively with MREG are significantly associated with sleep architecture and cognitive performance in older adults. These findings underscore the potential of MREG to assess glymphatic function and provide important insights into the mechanisms linking sleep disturbances, cognitive decline, and aging. The identified correlations between pulsations and specific brain regions highlight potential pathways through which impaired glymphatic function could contribute to cognitive decline in older adults, suggesting promising avenues for future clinical and research applications.
类淋巴系统通过脑脊液（CSF）沿血管周围间隙的流动促进大脑中废物的有效清除。动物研究表明，类淋巴系统的效率会随着年龄的增长而下降，但人类中这种下降的证据有限。我们推测，老年人类淋巴系统效率降低可能与睡眠质量随年龄增长而恶化有关，这可能导致认知障碍。
20名年龄≥60岁的参与者提供了多维度认知测量、整夜多导睡眠图，以及在多导睡眠图后的早晨进行的磁共振脑成像（MREG）。MREG是一种单次三维（3D）序列，采用螺旋堆叠球形轨迹对3D k空间进行欠采样，能够每100毫秒采集一次全脑数据，以无创且动态地评估大脑生理脉动。频谱功率和光流分析量化了心血管（CvB；0.52 - 1.6赫兹）、呼吸（RFB；0.11 - 0.44赫兹）和低频（LFB；0.008 - 0.1赫兹）频段内的生理脉动。这些测量结果与整夜多导睡眠图评估的认知测试分数和睡眠参数相关。
生理脉动、睡眠和认知测量之间出现了显著关联。心血管脉动强度与非快速眼动（NREM）第3阶段（N3）睡眠百分比相关（右额极峰值体素；r = 0.72，p < 0.001）以及语言领域表现相关（左距状回；r = 0.56，p = 0.01）。呼吸脉动与入睡潜伏期密切相关（右颞下回；r = 0.75，p < 0.001）。此外，低频脉动与入睡潜伏期相关（右中央前回；r = 0.67，p = 0.002）。这些发现表明，由脑脉动反映的类淋巴系统效率与老年人的睡眠质量和认知表现密切相关，尤其涉及与认知和睡眠调节功能相关的皮质和皮质下结构。
本研究独特地表明，通过MREG无创测量的大脑生理脉动与老年人的睡眠结构和认知表现显著相关。这些发现强调了MREG评估类淋巴功能的潜力，并为连接睡眠障碍、认知衰退和衰老的机制提供了重要见解。所确定的脉动与特定脑区之间的相关性突出了类淋巴功能受损可能导致老年人认知衰退的潜在途径，为未来的临床和研究应用提出了有前景的方向。
