Guo Hai-Hua, Liang Dong-Xin, Zhang Qun, Fu Yan, Huang Liang-Yu, Sheng Ze-Hu, Tan Lan, Wang Zuo-Teng
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
Department of Neurology, Qingdao Eight People's Hospital, Qingdao, 266100, China.
Transl Psychiatry. 2025 May 16;15(1):169. doi: 10.1038/s41398-025-03389-1.
The relationship between sleep quality, neurofilament light chain (NFL), and cognitive impairment, including the potential effect of plasma NFL in this association, remains unclear. Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we excluded individuals with dementia or a history of sleep-related medication use at baseline, including 640 participants with complete sleep assessments and covariates. Sleep quality was assessed using the Neuropsychiatric Inventory sleep subscale, which includes ratings of frequency, severity, and their product, with higher scores indicating poorer sleep quality. Baseline and follow-up demographics, sleep indices, plasma NFL levels, and cognition scores (including Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS13], Clinical Dementia Rating Scale-Sum of Boxes [CDRSB], Executive Function [EF], Language [LAN], and Memory [MEM]) were also collected. Multivariable linear regression examined the associations between baseline sleep quality, plasma NFL, and cognition, as well as the relationship between sleep quality and longitudinal cognitive decline, calculated using linear mixed-effects models. Mediation analysis evaluated the role of plasma NFL in the sleep-cognition association. Multiple testing significance was corrected using false discovery rate, with results presented as Q-values. Poor sleep quality scores were associated with elevated plasma NFL levels (β: 0.055 to 2.645, P < 0.05), poorer cognition (ADAS13, CDRSB, EF, LAN, MEM; β: -0.188 to 1.279, Q < 0.05), and accelerated longitudinal cognitive decline (MoCA; β: -0.005, Q < 0.05) in both models, with sensitivity analyses supporting these findings. Furthermore, plasma NFL levels partially mediated the relationship between sleep quality and both baseline cognition (ADAS13, CDRSB, LAN, MEM; P < 0.05) and longitudinal cognitive decline (MoCA; P < 0.05), with mediation proportions ranging from 9.2% to 26.7%. Poorer sleep quality was associated with cognitive impairment and accelerated cognitive decline, suggesting its potential role in Alzheimer's disease. These associations may be partially mediated by neuroaxonal injury.
睡眠质量、神经丝轻链（NFL）与认知障碍之间的关系，包括血浆NFL在这种关联中的潜在作用，仍不明确。利用阿尔茨海默病神经影像学倡议（ADNI）队列，我们排除了基线时患有痴呆症或有睡眠相关药物使用史的个体，包括640名有完整睡眠评估和协变量的参与者。使用神经精神科问卷睡眠子量表评估睡眠质量，该量表包括频率、严重程度及其乘积的评分，得分越高表明睡眠质量越差。还收集了基线和随访时的人口统计学数据、睡眠指标、血浆NFL水平和认知分数（包括简易精神状态检查表[MMSE]、蒙特利尔认知评估[MoCA]、阿尔茨海默病评估量表-认知子量表[ADAS13]、临床痴呆评定量表-方框总和[CDRSB]、执行功能[EF]、语言[LAN]和记忆[MEM]）。多变量线性回归分析了基线睡眠质量、血浆NFL与认知之间的关联，以及睡眠质量与纵向认知衰退之间的关系，纵向认知衰退使用线性混合效应模型计算。中介分析评估了血浆NFL在睡眠-认知关联中的作用。使用错误发现率校正多重检验显著性，结果以Q值表示。睡眠质量差的分数与血浆NFL水平升高（β：0.055至2.645，P < 0.05）、认知能力较差（ADAS13、CDRSB、EF、LAN、MEM；β：-0.188至1.279，Q < 0.05）以及在两个模型中加速的纵向认知衰退（MoCA；β：-0.005，Q < 0.05）相关，敏感性分析支持这些发现。此外，血浆NFL水平部分介导了睡眠质量与基线认知（ADAS13、CDRSB、LAN、MEM；P < 0.05）和纵向认知衰退（MoCA；P < 0.05）之间的关系，中介比例范围为9.2%至26.7%。较差的睡眠质量与认知障碍和加速的认知衰退相关，表明其在阿尔茨海默病中的潜在作用。这些关联可能部分由神经轴突损伤介导。
