Caga Jashelle, Tu Sicong, Dharmadasa Thanuja, Tse Nga Y, Zoing Margaret C, Huynh William, Mahoney Colin, Ahmed Rebekah M, Kiernan Matthew C
Brain & Mind Centre, University of Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Brain & Mind Centre, University of Sydney, NSW, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
Cortex. 2021 Dec;145:341-349. doi: 10.1016/j.cortex.2021.02.029. Epub 2021 Mar 23.
Apathy is the core behavioural feature of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS). Initiation and emotional manifestations of apathy significantly affect patients and carers, particularly in terms of quality of life. As such, the primary aim of the present study was to investigate the prevalence and neural correlates of initiation, and emotional subtypes of apathy in ALS. A total of 109 participants were recruited from a specialised, tertiary referral ALS/FTD clinic. Overall rates of apathy, including cognitive, initiation and emotion subtypes as assessed by the Dimensional Apathy Scale (DAS), were examined and correlated with brain volumes, including voxel-based morphometry on high resolution MRI. Clinically significant apathy ranged between 49% (patient-rated DAS) and 64% (carer-rated DAS), with the most common apathy subtypes being initiation (84-96%) and emotional (74-75%) apathy. The results of the two-way repeated measures ANOVA revealed significant differences across the DAS executive, emotional and initiation subscales (p = .0001). Multivariate analysis using a logistic regression model showed that only initiation; (odds ratio = 3.08, p = .004) and emotional (odds ratio = 2.40, p = .008) apathy were predictive of clinically significant apathy, controlling for education and depression. Increased initiation apathy correlated with reduced grey matter within bilateral superior frontal gyrus and increased emotional apathy correlated with reduced grey matter in prefrontal cortices and right anterior cingulate, previously implicated in apathy. Additional correlations were identified including the angular gyrus (or the temporo-parietal junction), important in reward valuation and subsequent goal-directed behaviour. Taken together, results from the present series highlight the frequency and multi-dimensionality of apathy in ALS. The pathophysiological mechanisms of apathy in ALS may be critically underpinned by neurodegeneration across a distributed brain network, with key roles in task initiation, emotion, reward processing and subsequent goal-directed behaviour.
冷漠是肌萎缩侧索硬化症（ALS）额颞叶功能障碍的核心行为特征。冷漠的起始及情感表现对患者及其照料者有显著影响，尤其是在生活质量方面。因此，本研究的主要目的是调查ALS中冷漠起始及情感亚型的患病率和神经关联。总共从一家专业的三级转诊ALS/FTD诊所招募了109名参与者。通过维度冷漠量表（DAS）评估的包括认知、起始和情感亚型在内的总体冷漠率进行了检查，并与脑容量相关联，包括基于体素的高分辨率MRI形态测量。具有临床意义的冷漠率在49%（患者评定的DAS）至64%（照料者评定的DAS）之间，最常见的冷漠亚型是起始型（84 - 96%）和情感型（74 - 75%）冷漠。双向重复测量方差分析结果显示，DAS执行、情感和起始子量表之间存在显著差异（p = .0001）。使用逻辑回归模型的多变量分析表明，仅起始型（优势比 = 3.08，p = .004）和情感型（优势比 = 2.40，p = .008）冷漠可预测具有临床意义的冷漠，同时控制了教育程度和抑郁因素。起始型冷漠增加与双侧额上回灰质减少相关，情感型冷漠增加与前额叶皮质和右侧前扣带回灰质减少相关，这些脑区先前已被认为与冷漠有关。还发现了其他相关性，包括在奖励评估及随后的目标导向行为中起重要作用的角回（或颞顶联合区）。总体而言，本系列研究结果突出了ALS中冷漠的频率和多维度性。ALS中冷漠的病理生理机制可能关键地由分布在整个脑网络中的神经退行性变所支撑，在任务起始、情感、奖励处理及随后的目标导向行为中起关键作用。
