Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea.
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul, 135-710, Republic of Korea.
Alzheimers Res Ther. 2019 Jan 22;11(1):10. doi: 10.1186/s13195-018-0462-z.
Although amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer's disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by clinical dementia rating sum of boxes (CDR-SOB). Then, we compared the clinical and neuroimaging features among groups classified by cognitive trajectory.
We retrospectively recruited 278 patients with aMCI who underwent three or more timepoints of neuropsychological testing. They also had magnetic resonance imaging (MRI) including structured three-dimensional volume images. Cortical thickness was measured using surface-based methods. We performed trajectory analyses to classify our aMCI patients according to their progression and investigate their cognitive trajectory using CDR-SOB.
Trajectory analyses showed that patients with aMCI were divided into three groups: stable (61.8%), slow decliner (31.7%), and fast decliner (6.5%). Changes throughout a mean follow-up duration of 3.7 years in the CDR-SOB for the subgroups of stable/slow/fast decliners were 1.3-, 6.4-, and 12-point increases, respectively. Decliners were older and carried apolipoprotein E4 (APOE4) genotypes more frequently than stable patients. Compared with the stable group, decliners showed a higher frequency of aMCI patients with both visual and verbal memory dysfunction, late stage aMCI, and multiple domain dysfunction. In addition, compared with the stable group, the slow decliners showed cortical thinning predominantly in bilateral parietotemporal areas, while the fast decliners showed cortical thinning predominantly in bilateral frontotemporal areas. Both decliner groups showed worse cognitive function in attention, language, visuospatial, memory, and frontal/executive domains than the stable group.
Our data-driven trajectory analysis provides new insights into heterogeneous cognitive trajectories of aMCI and further suggests that baseline clinical and neuroimaging profiles might predict aMCI patients with poor prognosis.
虽然遗忘型轻度认知障碍（aMCI）通常被认为是阿尔茨海默病的前驱阶段，但 aMCI 患者的进展模式存在异质性。此外，很少有研究调查 aMCI 中数据驱动的认知轨迹。因此，我们根据临床痴呆评定量表总和分（CDR-SOB）测量的认知轨迹对 aMCI 患者进行分类，然后比较按认知轨迹分类的组之间的临床和神经影像学特征。
我们回顾性招募了 278 名接受了三次或更多次神经心理学测试的 aMCI 患者。他们还接受了包括结构三维容积图像在内的磁共振成像（MRI）检查。使用基于表面的方法测量皮质厚度。我们进行轨迹分析，根据患者的进展情况对 aMCI 患者进行分类，并使用 CDR-SOB 研究他们的认知轨迹。
轨迹分析显示，aMCI 患者分为三组：稳定组（61.8%）、缓慢下降组（31.7%）和快速下降组（6.5%）。在稳定/缓慢/快速下降亚组中，CDR-SOB 的平均随访时间为 3.7 年，其变化分别为 1.3、6.4 和 12 个点的增加。下降组患者年龄较大，携带载脂蛋白 E4（APOE4）基因型的频率也较高。与稳定组相比，下降组患者中视觉和语言记忆功能障碍、晚期 aMCI 和多域功能障碍的 aMCI 患者比例更高。此外，与稳定组相比，缓慢下降组患者双侧顶颞区皮质变薄更为明显，而快速下降组患者双侧额颞区皮质变薄更为明显。与稳定组相比，下降组患者在注意力、语言、视空间、记忆和额叶/执行域的认知功能更差。
我们的数据驱动轨迹分析为 aMCI 的异质认知轨迹提供了新的见解，并进一步表明基线临床和神经影像学特征可能预测预后不良的 aMCI 患者。
