Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, 165 Cambridge Street, Suite 600, Boston, MA, 02114, USA.
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
Brain Imaging Behav. 2021 Oct;15(5):2540-2551. doi: 10.1007/s11682-021-00456-1. Epub 2021 Feb 15.
Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) may present typical behavioral variant FTD symptoms. This study aims to determine whether profile and severity of cognitive-behavioral symptoms in ALS/ALS-FTD are predicted by regional cortical atrophy. The hypothesis is that executive dysfunction can be predicted by dorsolateral prefrontal cortical (dlPFC) atrophy, apathy by dorsomedial PFC (dmPFC) and anterior cingulate cortical (ACC) atrophy, disinhibition by orbitofrontal cortical (OFC) atrophy. 3.0 Tesla MRI scans were acquired from 22 people with ALS or ALS-FTD. Quantitative cortical thickness analysis was performed with FreeSurfer. A priori-defined regions of interest (ROI) were used to measure cortical thickness in each participant and calculate magnitude of atrophy in comparison to 115 healthy controls. Spearman correlations were used to evaluate associations between frontal ROI cortical thickness and cognitive-behavioral symptoms, measured by Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinical Dementia Rating (CDR) scale. ALS-FTD participants exhibited variable degrees of apathy (NPI-Q/apathy: 1.6 ± 1.2), disinhibition (NPI-Q/disinhibition: 1.2 ± 1.2), executive dysfunction (CDR/judgment-problem solving: 1.7 ± 0.8). Within the ALS-FTD group, executive dysfunction correlated with dlPFC atrophy (ρ:-0.65;p < 0.05); similar trends were seen for apathy with ACC (ρ:-0.53;p < 0.10) and dmPFC (ρ:-0.47;p < 0.10) atrophy, for disinhibition with OFC atrophy (ρ:-0.51;p < 0.10). Compared to people with ALS, those with ALS-FTD showed more diffuse atrophy involving precentral gyrus, prefrontal, temporal regions. Profile and severity of cognitive-behavioral symptoms in ALS-FTD are predicted by regional prefrontal atrophy. These findings are consistent with established brain-behavior models and support the role of quantitative MRI in diagnosis, management, counseling, monitoring and prognostication for a neurodegenerative disorder with diverse phenotypes.
肌萎缩侧索硬化-额颞叶痴呆（ALS-FTD）可能表现出典型的行为变异额颞叶痴呆症状。本研究旨在确定 ALS/ALS-FTD 患者的认知行为症状的特征和严重程度是否可由皮质区域性萎缩来预测。假设是执行功能障碍可以由背外侧前额叶皮质（dlPFC）萎缩来预测，冷漠可以由背内侧前额叶皮质（dmPFC）和前扣带皮质（ACC）萎缩来预测，冲动控制障碍可以由眶额皮质（OFC）萎缩来预测。从 22 名患有 ALS 或 ALS-FTD 的人中采集了 3.0T MRI 扫描。使用 FreeSurfer 进行定量皮质厚度分析。使用预先定义的感兴趣区域（ROI）测量每位参与者的皮质厚度，并与 115 名健康对照者比较计算萎缩程度。使用 Spearman 相关性评估额叶 ROI 皮质厚度与认知行为症状（由神经精神疾病问卷（NPI-Q）和临床痴呆评定量表（CDR）评定）之间的关联。ALS-FTD 患者表现出不同程度的冷漠（NPI-Q/冷漠：1.6±1.2）、冲动控制障碍（NPI-Q/冲动控制障碍：1.2±1.2）、执行功能障碍（CDR/判断解决问题：1.7±0.8）。在 ALS-FTD 组内，执行功能障碍与 dlPFC 萎缩相关（ρ：-0.65；p<0.05）；冷漠与 ACC（ρ：-0.53；p<0.10）和 dmPFC（ρ：-0.47；p<0.10）萎缩之间存在相似的趋势，冲动控制障碍与 OFC 萎缩（ρ：-0.51；p<0.10）之间也存在相似的趋势。与 ALS 患者相比，ALS-FTD 患者的前中央回、前额叶和颞叶区域存在更广泛的萎缩。ALS-FTD 患者的认知行为症状的特征和严重程度可由区域性前额叶萎缩来预测。这些发现与既定的脑-行为模型一致，并支持定量 MRI 在诊断、管理、咨询、监测和预测具有多种表型的神经退行性疾病中的作用。
