Gong Liang, Li Haoyu, Li Maoxia, He Yuan, Liu Duan, Zhou Wen, Zhang Bei, Xi Chunhua
Department of Neurology, West China School of Medicine, Sichuan University, Sichuan University Affiliated Chengdu Second People's Hospital, Chengdu, Sichuan 610017, China.
Department of Neurology, Chengdu Medical College, Chengdu Second People's Hospital, Chengdu, Sichuan 610017, China.
Brain Commun. 2025 Sep 9;7(5):fcaf341. doi: 10.1093/braincomms/fcaf341. eCollection 2025.
Sleep duration and Apolipoprotein E genotype are critical factors influencing Alzheimer's disease progression. This study investigates the interaction between sleep duration and Apolipoprotein E genotype on the functional connectivity of the locus coeruleus in clinically unimpaired older adults with elevated amyloid beta, a population at risk for pre-clinical Alzheimer's disease. The study included 692 clinically unimpaired older adults with elevated amyloid beta participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Study (A4). Resting-state functional MRI data were analysed to construct locus coeruleus-based functional connectivity networks, and a 2 × 2 analysis of covariance was conducted to examine the main and interactive effects of sleep duration (normal versus short sleep) and Apolipoprotein E genotype (ɛ4- versus ɛ4+) on locus coeruleus-functional connectivity. Structural equation modelling was used to explore whether locus coeruleus-functional connectivity mediated the relationship between age and cognitive performance. Significant main effects of sleep duration and Apolipoprotein E genotype on locus coeruleus-functional connectivity were observed in the right temporal pole, middle cingulate cortex, and superior temporal gyrus. An interactive effect of sleep and Apolipoprotein E genotype was noted, influencing left locus coeruleus-functional connectivity in regions in the precentral gyrus, and right locus coeruleus-functional connectivity network in the middle temporal gyrus and lateral orbitofrontal cortex. Mediation analysis revealed that locus coeruleus-functional connectivity in the middle cingulate cortex and lateral orbitofrontal cortex partially mediated age associated cognitive decline. These findings suggest that locus coeruleus-functional connectivity networks, influenced by sleep duration and Apolipoprotein E genotype, play a crucial role in cognitive aging, particularly in memory function. Understanding these interactions may inform early intervention strategies to preserve cognitive health in older adults at risk for Alzheimer's disease.
睡眠时间和载脂蛋白E基因型是影响阿尔茨海默病进展的关键因素。本研究调查了睡眠时间和载脂蛋白E基因型在临床上未受损但淀粉样蛋白β升高的老年人（这是一组处于临床前期阿尔茨海默病风险中的人群）中对蓝斑功能连接性的相互作用。该研究纳入了来自无症状阿尔茨海默病抗淀粉样蛋白治疗研究（A4）的692名临床上未受损且淀粉样蛋白β升高的老年人。分析静息态功能磁共振成像数据以构建基于蓝斑的功能连接网络，并进行2×2协方差分析以检验睡眠时间（正常睡眠与短睡眠）和载脂蛋白E基因型（ɛ4 -与ɛ4 +）对蓝斑功能连接性的主要和交互作用。使用结构方程模型来探究蓝斑功能连接性是否介导了年龄与认知表现之间的关系。在右侧颞极、中扣带回皮质和颞上回观察到睡眠时间和载脂蛋白E基因型对蓝斑功能连接性有显著的主要影响。注意到睡眠和载脂蛋白E基因型存在交互作用，影响中央前回区域的左侧蓝斑功能连接性，以及颞中回和外侧眶额皮质的右侧蓝斑功能连接网络。中介分析显示，中扣带回皮质和外侧眶额皮质的蓝斑功能连接性部分介导了与年龄相关的认知衰退。这些发现表明，受睡眠时间和载脂蛋白E基因型影响的蓝斑功能连接网络在认知衰老中起着关键作用，尤其是在记忆功能方面。了解这些相互作用可能为处于阿尔茨海默病风险中的老年人维持认知健康的早期干预策略提供依据。
