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Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort
Cortex ( IF 3.6 ) Pub Date : 2020-09-26 , DOI: 10.1016/j.cortex.2020.08.023
Lucy L Russell 1 , Caroline V Greaves 1 , Martina Bocchetta 1 , Jennifer Nicholas 2 , Rhian S Convery 1 , Katrina Moore 1 , David M Cash 3 , John van Swieten 4 , Lize Jiskoot 5 , Fermin Moreno 6 , Raquel Sanchez-Valle 7 , Barbara Borroni 8 , Robert Laforce 9 , Mario Masellis 10 , Maria Carmela Tartaglia 11 , Caroline Graff 12 , Emanuela Rotondo 13 , Daniela Galimberti 14 , James B Rowe 15 , Elizabeth Finger 16 , Matthis Synofzik 17 , Rik Vandenberghe 18 , Alexandre de Mendonça 19 , Fabrizio Tagliavini 20 , Isabel Santana 21 , Simon Ducharme 22 , Chris Butler 23 , Alex Gerhard 24 , Johannes Levin 25 , Adrian Danek 25 , Markus Otto 26 , Jason D Warren 1 , Jonathan D Rohrer 1 ,
Affiliation  

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease.



中文翻译:

GENFI 队列中遗传性额颞叶痴呆的社会认知障碍

额颞叶痴呆 (FTD) 的一个关键症状是难以与他人进行社交互动。FTD 中的社会认知问题包括情绪处理受损和心理困难理论,虽然这些问题已在散发性 FTD 中得到广泛研究,但很少有研究在家族性 FTD 中对其进行调查。面部情绪识别 (FER) 和失礼 (FP) 识别测试用于研究遗传性额颞叶痴呆倡议 (GENFI) 中的社会认知,这是一个由 C9orf72、GRN 和 MAPT 组成的大型家族FTD队列突变携带者。627 名参与者至少承担了一项任务,并被分为突变阴性健康对照、症状前突变携带者(分为早期和晚期组)和有症状突变携带者。使用线性回归模型对各组进行比较,并根据年龄、性别、教育和 FP 识别测试、语言进行自举调整。使用基于体素的形态测量学 (VBM) 研究探索了社会认知缺陷的神经相关性。所有三个有症状的遗传组在这两项任务上都受到损害,但它们之间没有显着差异。然而,在发病​​之前,只有晚期症状前的C9orf72与对照组相比,FER 测试中的突变携带者受到了损害,子分析显示了差异,特别是在恐惧和悲伤方面。VBM 分析表明,社会认知受损主要与左半球主要区域网络相关,特别涉及纹状体、眶额皮质和脑岛,以及较小程度的下内侧颞叶和额叶其他区域。总之,心理理论和情绪处理能力在家族性 FTD 中受损,在C9orf72症状前突变携带者中,早期变化发生在症状出现之前。未来的工作应该调查性能如何随时间变化,以便更清楚地了解疾病过程中的社会认知障碍。

更新日期:2020-11-21
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