3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.
3rd Neurology Unit and Motor Neuron Diseases Centre, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.
Neurosci Lett. 2021 May 29;754:135898. doi: 10.1016/j.neulet.2021.135898. Epub 2021 Apr 15.
Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease marked by progressive loss of motor abilities. Approximately half of patents with ALS experience cognitive (ALSci) or behavioural impairment (ALSbi) during the course of the disease, with a small percentage developing overt frontotemporal dementia (FTD). ALSci and/or ALSbi can occur simultaneously with motor neuron degeneration or develop in advanced stages of the disease, but it can even precede motor involvement in some cases, namely in ALS patients meeting criteria for FTD. Despite clear evidence that cognitive/behavioural impairment may appear early in the course of ALS, no prominent deterioration seems to occur with disease progression. Longitudinal studies have failed to reach conclusive results on the progression of cognitive and behavioural involvement in ALS. This may be due to some structural limitations of the studies, such as attrition rate, practice effect, short-time interval between neuropsychological assessments, but it can also be due to the heterogeneity of ALS phenotypes. The objective of this review is to provide a comprehensive and critical analysis of results of longitudinal studies highlighting cognitive and behavioural domains mainly affected by neurodegeneration pointing out the determinants that might be associate with the development and worsening of frontotemporal symptoms in ALS. At this regard, older age, rapidly progressing ALS, bulbar-onset, advanced disease stages are among factors mainly associated with cognitive and behavioural involvement. Moreover, the progression of cognitive and behavioural deficits seems to be not directly related to the slope of motor disability, thus suggesting the independence of neuropsychological and motor functional decline in ALS. Cognitive and motor involvement may indeed present with distinct trajectories suggesting a differential vulnerability of motor and non-motor cortical networks. In this scenario, determining the progression of extra-motor involvement in ALS may help refine understanding of the clinical implications of cognitive and behavioural abnormalities, and provide clues to the aetiology of the disease.
肌萎缩侧索硬化症（ALS）是一种异质性神经退行性疾病，其特征是运动能力进行性丧失。大约一半的 ALS 患者在疾病过程中会出现认知（ALSci）或行为障碍（ALSbi），一小部分患者会出现明显的额颞叶痴呆（FTD）。ALSci 和/或 ALSbi 可与运动神经元变性同时发生，也可在疾病晚期发生，但在某些情况下，甚至可能先于运动神经元受累，即在符合 FTD 标准的 ALS 患者中。尽管有明确的证据表明认知/行为障碍可能在 ALS 病程早期出现，但随着疾病的进展似乎没有明显的恶化。纵向研究未能就 ALS 认知和行为参与的进展得出明确的结果。这可能是由于研究的一些结构限制，如损耗率、练习效应、神经心理学评估之间的短时间间隔，但也可能是由于 ALS 表型的异质性。本综述的目的是对突出受神经退行性变影响的认知和行为领域的纵向研究结果进行全面和批判性分析，指出可能与 ALS 中额颞症状发展和恶化相关的决定因素。在这方面，年龄较大、进展迅速的 ALS、球部起病、疾病晚期是与认知和行为参与主要相关的因素。此外，认知和行为缺陷的进展似乎与运动功能障碍的斜率没有直接关系，这表明 ALS 中神经心理学和运动功能的下降是独立的。认知和运动参与确实可能具有不同的轨迹，这表明运动和非运动皮质网络的易感性不同。在这种情况下，确定 ALS 中运动外参与的进展可能有助于深入了解认知和行为异常的临床意义，并为疾病的病因提供线索。
