Kim Seong Jae, Lee Jung Hie, Jang Jae-Won, Choi Minseo, Suh In Bum
Department of Psychiatry, College of Medicine, Chosun University, Gwangju 61452, Republic of Korea.
Department of Psychiatry, College of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.
J Clin Med. 2025 Aug 4;14(15):5481. doi: 10.3390/jcm14155481.
: Rest-activity rhythm (RAR) disturbances can contribute to aging and dementia via metabolic dysregulation. Hydroxycholesterol (OH) is thought to mediate the link between hypercholesterolemia and neurodegeneration. This study compared sleep and RAR parameters between amnestic mild cognitive impairment (aMCI) patients and normal controls (NCs), and examined their associations with plasma 27-OH levels, reflecting peripheral cholesterol metabolism. In total, 18 aMCI patients (76.6 ± 6.1 years) and 21 NCs (70.4 ± 6.7 years) underwent five-day actigraphy and dim light melatonin onset assessment. Plasma 27-OH levels were measured via high-performance liquid chromatography-mass spectrometry. Generalized linear models (GLMs) were used to analyze the relationships between sleep, RAR, and 27-OH levels. : The aMCI group had significantly lower 27-OH levels and 27-OH/total cholesterol ratios ( < 0.05). GLM revealed that longer sleep onset latency (SOL) was associated with higher 27-OH levels in aMCI, distinguishing them from NCs. Additionally, in aMCI, longer SOL, lower sleep efficiency (SE), and higher fragmentation index (FI) were associated with an increased 27-OH/total cholesterol ratio ( < 0.05). Higher relative amplitude of RAR was linked to lower 27-OH levels across groups ( < 0.01), but RAR parameters showed no significant association with the 27-OH/total cholesterol ratio. Sleep disturbances, including prolonged SOL, reduced SE, and increased FI, were associated with altered peripheral cholesterol oxygenation in aMCI. Greater RAR amplitude correlated with lower 27-OH levels, regardless of cognitive status. These findings suggest that peripheral cholesterol oxygenation in aMCI is related to both sleep disturbances and circadian rhythm dysregulation, highlighting their role in cholesterol metabolism and neurodegeneration.
静息 - 活动节律（RAR）紊乱可通过代谢失调导致衰老和痴呆。羟基胆固醇（OH）被认为介导了高胆固醇血症与神经退行性变之间的联系。本研究比较了遗忘型轻度认知障碍（aMCI）患者和正常对照（NCs）的睡眠和RAR参数，并研究了它们与反映外周胆固醇代谢的血浆27 - OH水平之间的关联。总共18名aMCI患者（76.6±6.1岁）和21名NCs（70.4±6.7岁）接受了为期五天的活动记录仪监测和暗光褪黑素起始评估。通过高效液相色谱 - 质谱法测量血浆27 - OH水平。使用广义线性模型（GLMs）分析睡眠、RAR和27 - OH水平之间的关系。aMCI组的27 - OH水平和27 - OH/总胆固醇比值显著更低（<0.05）。GLM显示，在aMCI中，更长的入睡潜伏期（SOL）与更高的27 - OH水平相关，这将他们与NCs区分开来。此外，在aMCI中，更长的SOL、更低的睡眠效率（SE）和更高的碎片化指数（FI）与更高的27 - OH/总胆固醇比值相关（<0.05）。RAR的相对振幅更高与各组中更低的27 - OH水平相关（<0.01），但RAR参数与27 - OH/总胆固醇比值无显著关联。睡眠障碍，包括延长的SOL、降低的SE和增加的FI，与aMCI中外周胆固醇氧化改变有关。无论认知状态如何，更大的RAR振幅与更低的27 - OH水平相关。这些发现表明，aMCI中外周胆固醇氧化与睡眠障碍和昼夜节律失调均有关，突出了它们在胆固醇代谢和神经退行性变中的作用。
