University of Ulm, Department of Neurology, Germany.
University of Ulm, Department of Neurology, Germany.
Cortex. 2018 Apr;101:163-171. doi: 10.1016/j.cortex.2018.01.004. Epub 2018 Jan 31.
Sequential spread of TDP-43 load in the brain may be a pathological characteristic of amyotrophic lateral sclerosis (ALS). Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) based marker of this pathological feature. Cognitive deficits known to be present in a subset of ALS patients might act as an additional in vivo clinical marker of disease spread. N = 139 patients with ALS were tested with the Edinburgh Cognitive and Behavioural ALS screen (ECAS) in addition to DTI brain measures of pathological spread. Executive function, memory and disinhibited behaviour were selected for Cognitive-Staging criteria, as these cognitive functions are attributed to cerebral areas analogous to the pattern of MRI markers of TDP-43 pathology. ROC curve analyses were performed to define cut-off scores for cognitive stages 2 (executive function), stage 3 (disinhibited behaviour) and stage 4 (memory), and staging was performed according to the cognitive profile subsequently. Associations of Cognitive-Staging (stage 2-4) and MRI-Staging measures were determined. In total, 77 patients (55%) performed below ROC cut-off scores in either executive function or memory or both and/or were reported to have disinhibited behaviour which permitted Cognitive-Staging. The cognitive profile of patients with discrete MRI stages 2-4 correlated significantly with DTI parameters. For those patients with cognitive impairment, there was a high congruency between MRI and Cognitive-Staging with high specificity and sensitivity of executive functions for MRI stage 2, disinhibited behaviour for MRI stage 3 and moderate of memory for MRI stage 4. Cognitive impairment follows specific patterns in ALS and these patterns can be used for Cognitive-Staging with a high specificity compared to MRI-Staging. For the individual, cognitive screening is a fast and easy to apply measurement of cerebral function giving valuable information in a clinical context.
TDP-43 负荷在大脑中的顺序传播可能是肌萎缩侧索硬化症 (ALS) 的病理特征。扩散张量成像 (DTI) 是这种病理特征的磁共振成像 (MRI) 标志物。已知在一部分 ALS 患者中存在认知缺陷，可能作为疾病传播的另一个体内临床标志物。除了 DTI 大脑病理传播测量外，还对 139 名 ALS 患者进行了爱丁堡认知和行为 ALS 筛查 (ECAS) 测试。选择执行功能、记忆和去抑制行为作为认知分期标准，因为这些认知功能归因于与 TDP-43 病理学 MRI 标志物模式类似的大脑区域。进行 ROC 曲线分析，以确定认知阶段 2（执行功能）、阶段 3（去抑制行为）和阶段 4（记忆）的截断分数，并根据随后的认知特征进行分期。确定认知分期（阶段 2-4）和 MRI 分期测量之间的关联。共有 77 名患者（55%）在执行功能或记忆或两者均低于 ROC 截断分数，或报告有去抑制行为，从而允许进行认知分期。具有离散 MRI 阶段 2-4 的患者的认知特征与 DTI 参数显著相关。对于那些认知障碍的患者，MRI 和认知分期之间存在高度一致性，执行功能对 MRI 阶段 2、去抑制行为对 MRI 阶段 3 和记忆对 MRI 阶段 4 的特异性和敏感性均较高。认知障碍在 ALS 中呈现出特定的模式，与 MRI 分期相比，这些模式可用于认知分期，具有较高的特异性。对于个体而言，认知筛查是一种快速且易于应用的大脑功能测量方法，可以在临床环境中提供有价值的信息。
