Chen Yu, Landin-Romero Ramon, Kumfor Fiona, Irish Muireann, Hodges John R, Piguet Olivier
The University of Sydney, School of Psychology, Sydney, NSW, Australia; The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia.
The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia; The University of Sydney, Sydney Medical School, Sydney, NSW, Australia.
Cortex. 2020 Aug;129:57-67. doi: 10.1016/j.cortex.2020.04.013. Epub 2020 Apr 28.
Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specific cerebellar grey matter atrophy has been associated with cognitive dysfunction in FTD; however, the extent and severity of structural abnormalities in the cerebro-cerebellar circuits in these disorders has not been investigated. This study aimed to identify patterns of cerebellar white matter changes and their relations to cognitive deficits in the main FTD subtypes. Results revealed bilateral cerebellar white matter changes in all FTD subtypes compared with controls, with greater cerebellar white matter changes in bvFTD than SD and PNFA. Both afferent and efferent cerebellar pathways were associated with cognition. The profiles of the involvement of cerebellar pathways in cognition varied across FTD syndromes. In bvFTD, the output pathway of the cerebellum was only associated with measures of episodic memory. The input pathway was associated with measures of attention, working memory, visuospatial, episodic memory, executive function, and emotion. In SD, both the output and input pathways were associated with measures of working memory, language, and emotion. Finally, in PNFA, both the output and input pathway of the cerebellum were associated with attention, language, and executive function. Additionally, the input pathway was associated with working memory, visuospatial, and emotion. This study is the first to identify patterns of cerebellar white matter changes across FTD syndromes, which in turn relate to cognitive deficits. These findings extend our understanding of the cerebro-cerebellar networks and provide new insight into the role of cerebellar white matter in cognition.
额颞叶痴呆（FTD）是一组异质性神经退行性脑疾病，主要影响额叶和/或颞叶。目前已识别出三种主要亚型，每种亚型都有独特的临床和认知特征：行为变异型FTD（bvFTD）、语义性痴呆（SD）和进行性非流利性失语（PNFA）。特定亚型的小脑灰质萎缩与FTD中的认知功能障碍有关；然而，这些疾病中脑-小脑回路结构异常的程度和严重程度尚未得到研究。本研究旨在确定主要FTD亚型中小脑白质变化的模式及其与认知缺陷的关系。结果显示，与对照组相比，所有FTD亚型均存在双侧小脑白质变化，bvFTD的小脑白质变化大于SD和PNFA。小脑的传入和传出通路均与认知有关。小脑通路参与认知的特征在不同的FTD综合征中有所不同。在bvFTD中，小脑的输出通路仅与情景记忆指标相关。输入通路与注意力、工作记忆、视觉空间、情景记忆、执行功能和情绪指标相关。在SD中，输出和输入通路均与工作记忆、语言和情绪指标相关。最后，在PNFA中，小脑的输出和输入通路均与注意力、语言和执行功能相关。此外，输入通路还与工作记忆、视觉空间和情绪相关。本研究首次确定了不同FTD综合征中小脑白质变化的模式，这些模式又与认知缺陷相关。这些发现扩展了我们对脑-小脑网络的理解，并为小脑白质在认知中的作用提供了新的见解。
