Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Cardiovascular and Neuroradiological Multimodal Imaging Unit, G. Monasterio Foundation-National Research Council/Tuscany Region, Pisa, Italy.
Eur J Neurol. 2023 Jan;30(1):32-46. doi: 10.1111/ene.15556. Epub 2022 Oct 3.
Human neuropathological studies indicate that the pontine nucleus Locus Coeruleus (LC) undergoes significant and early degeneration in Alzheimer's disease. This line of evidence alongside experimental data suggests that the LC functional/structural decay may represent a critical factor for Alzheimer's disease pathophysiological and clinical progression. In the present prospective study, we used Magnetic Resonance Imaging (MRI) with LC-sensitive sequence (LC-MRI) to investigate in vivo the LC involvement in Alzheimer's disease progression, and whether specific LC-MRI features at baseline are associated with prognosis and cognitive performance in amnestic Mild Cognitive Impairment.
LC-MRI parameters were measured at baseline by a template-based method on 3.0-T magnetic resonance images in 34 patients with Alzheimer's disease dementia, 73 patients with amnestic Mild Cognitive Impairment, and 53 cognitively intact individuals. A thorough neurological and neuropsychological assessment was performed at baseline and 2.5-year follow-up.
In subjects with Mild Cognitive Impairment who converted to dementia (n = 32), the LC intensity and number of LC-related voxels were significantly lower than in cognitively intact individuals, resembling those observed in demented patients. Such a reduction was not detected in Mild Cognitive Impairment individuals, who remained stable at follow-up. In Mild Cognitive Impairment subjects converting to dementia, LC-MRI parameter reduction was maximal in the rostral part of the left nucleus. Structural equation modeling analysis showed that LC-MRI parameters positively correlate with cognitive performance.
Our findings highlight a potential role of LC-MRI for predicting clinical progression in Mild Cognitive Impairment and support the key role of LC degeneration in the Alzheimer clinical continuum.
人体神经病理学研究表明，阿尔茨海默病患者的脑桥蓝斑核（LC）发生显著且早期的退行性变。这一证据与实验数据表明，LC 的功能/结构衰减可能是阿尔茨海默病病理生理和临床进展的关键因素。在本前瞻性研究中，我们使用磁共振成像（MRI）与 LC 敏感序列（LC-MRI）来研究 LC 在阿尔茨海默病进展中的体内参与情况，以及基线时的特定 LC-MRI 特征是否与遗忘型轻度认知障碍的预后和认知表现相关。
通过基于模板的方法在 3.0-T 磁共振图像上测量 34 例阿尔茨海默病痴呆患者、73 例遗忘型轻度认知障碍患者和 53 例认知正常个体的 LC-MRI 参数。在基线和 2.5 年随访时进行了全面的神经学和神经心理学评估。
在转化为痴呆的轻度认知障碍患者（n=32）中，LC 强度和 LC 相关体素数量明显低于认知正常个体，类似于痴呆患者的情况。在未转化为痴呆的轻度认知障碍患者中未检测到这种减少，这些患者在随访中保持稳定。在转化为痴呆的轻度认知障碍患者中，LC-MRI 参数减少最大的部位是左侧核的前半部分。结构方程模型分析显示，LC-MRI 参数与认知表现呈正相关。
我们的研究结果突出了 LC-MRI 在预测轻度认知障碍临床进展中的潜在作用，并支持 LC 退行性变在阿尔茨海默病临床连续体中的关键作用。
