基于PET/MR探索肌萎缩侧索硬化-额颞叶痴呆谱系疾病认知功能障碍的脑代谢与结构机制研究

Both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are rapidly progressing neurological degenerative diseases. They can be superimposed on each other genetically, pathologically, and clinically, and they are considered to belong to the same spectrum disease, namely frontotemporal spectrum disorder of ALS (ALS- FTSD). The cognitive function of patients constitutes a continuous change between ALS and FTD, and the intrinsic mechanism of this continuous change might be the key to unravel the nature of the disorder. Previous studies and the applicants' earlier investigations have shown that the brain metabolism/perfusion alterations and structural changes in ALS-FTSD patients are not completely parallel, and the mismatched regions might be the initiating factors of cognitive dysfunction in ALS. We intend to enroll ALS patients with different degrees of cognitive impairment and FTD patients to establish a complete ALS-FTSD cognitive phenotype database, and apply the integrated PET/MR to simultaneously acquire patients' brain metabolism and structural imaging data. Through cross-sectional comparisons among subgroups and different imaging techniques and longitudinal follow-ups, we attempt to explain the mechanisms underlying cognitive dysfunction in patients with ALS. The research results will help deepen the understanding of the pathogenesis of ALS-FTSD and its natural history, and provide basis for the development of rational clinical management strategies and imaging evaluation systems.

肌萎缩侧索硬化（ALS）与额颞叶痴呆（FTD）均是快速进展的神经系统变性疾病，两者在基因、病理及临床上可广泛叠加，目前认为二者属于同一谱系疾病（ALS-FTSD）。患者的认知功能障碍在ALS与FTD间存在连续变化，解释这种连续变化的内在机制有望成为解开疾病本质的关键。既往研究及申请人前期的探索均显示ALS-FTSD患者的脑代谢/血流变化与结构改变并不完全平行，两者的不匹配区可能是ALS发生认知功能障碍的始动因素。本研究拟入组不同程度认知功能障碍的ALS及单纯FTD患者，建立完整的ALS-FTSD认知表型库，应用一体化PET/MR同时采集患者的脑代谢及结构影像数据，通过横断面各亚组间、各影像学技术间的比较及纵向随访，尝试解释ALS发生认知功能障碍的始动机制。研究成果将有助于加深对ALS-FTSD致病机理及其自然发展过程的理解，为制定合理的临床管理策略及影像学评价体系提供依据。

肌萎缩侧索硬化（ALS）与额颞叶痴呆（FTD）均是快速进展的神经系统变性疾病，两者在基因、病理及临床上可广泛叠加，目前认为二者属于同一谱系疾病（ALS-FTD）。患者的认知功能障碍在ALS与FTD间存在连续变化，解释这种连续变化的内在机制有望成为解开疾病本质的关键。ALS-FTD预后较单纯的ALS或FTD更差。有研究发现认知障碍起病的ALS-FTD（cognitive onset ALS-FTD, ALS-FTD-C）中位生存期要显著长于运动障碍起病的患者（motor onset ALS-FTD, ALS-FTD-M），但两亚组间病理生理机制的差异尚不明确。本研究通过多模态影像学技术比较了认知障碍起病与运动障碍起病ALS-FTD脑灰质结构、脑血流量及脑白质纤维的差异。8例ALS-FTD-C、6例ALS-FTD-M及20例健康对照者完成了MRI扫描，应用基于体素的分析方法对两亚组的脑灰质体积及脑血流量进行了比较。研究发现ALS-FTD-C与ALS-FTD-M患者有各自的皮层萎缩和灌注模式，ALS-FTD-C与ALS-FTD-M相比有更显著的皮层萎缩和低灌注。本研究结果初步揭示了不同ALS-FTD亚组患者的病理学差异，有助于对ALS-FTD患者进行进一步分层探索。