Russell Lucy L, Greaves Caroline V, Bocchetta Martina, Nicholas Jennifer, Convery Rhian S, Moore Katrina, Cash David M, van Swieten John, Jiskoot Lize, Moreno Fermin, Sanchez-Valle Raquel, Borroni Barbara, Laforce Robert, Masellis Mario, Tartaglia Maria Carmela, Graff Caroline, Rotondo Emanuela, Galimberti Daniela, Rowe James B, Finger Elizabeth, Synofzik Matthis, Vandenberghe Rik, de Mendonça Alexandre, Tagliavini Fabrizio, Santana Isabel, Ducharme Simon, Butler Chris, Gerhard Alex, Levin Johannes, Danek Adrian, Otto Markus, Warren Jason D, Rohrer Jonathan D
Dementia Research Centre, Department of Neurodegenerative Disease, London, UK.
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK; Institute of Prion Disease, UCL Queen Square Institute of Neurology, London, UK.
Cortex. 2020 Dec;133:384-398. doi: 10.1016/j.cortex.2020.08.023. Epub 2020 Sep 26.
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.
额颞叶痴呆（FTD）的一个关键症状是在社交互动方面存在困难。FTD中的社会认知问题包括情感加工受损和心理理论障碍，虽然这些问题在散发性FTD中已得到广泛研究，但在家族性FTD中的研究却很少。面部表情识别（FER）和失礼（FP）识别测试被用于在遗传额颞叶痴呆倡议（GENFI）中研究社会认知，GENFI是一个由C9orf72、GRN和MAPT突变携带者组成的大型家族性FTD队列。627名参与者至少完成了一项任务，并被分为突变阴性健康对照组、症状前突变携带者（分为早期和晚期组）和症状性突变携带者。使用带有自抽样法的线性回归模型对各组进行比较，并对年龄、性别、教育程度以及FP识别测试中的语言进行了调整。使用基于体素的形态测量（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两项任务上均受损，且它们之间无显著差异。然而，在发病前，与对照组相比，只有晚期症状前C9orf72突变携带者在FER测试中受损，一项亚分析显示，尤其在恐惧和悲伤方面存在差异。VBM分析表明，受损的社会认知主要与以左半球为主的区域网络相关，这些区域特别涉及纹状体、眶额皮质和脑岛，在较小程度上还涉及颞叶内侧下部和额叶的其他区域。总之，家族性FTD患者的心理理论和情感加工能力受损，C9orf72症状前突变携带者在症状出现之前就出现了早期变化。未来的研究应调查随着时间推移表现如何变化，以便更清楚地了解疾病过程中的社会认知障碍。
