From the Department of Neurology, Vanderbilt University Medical Center, Nashville, TN.
Neurology. 2024 Dec 24;103(12):e210108. doi: 10.1212/WNL.0000000000210108. Epub 2024 Nov 25.
Frontotemporal lobar degeneration (FTLD) includes different clinical syndromes with distinct patterns of symptoms and neuroanatomical locations of neurodegeneration. However, FTLD is clinically heterogeneous (with overlapping symptoms across several domains) and neuroanatomically heterogeneous (with brain atrophy in different locations in different patients). Traditional methods struggle to fully account for this heterogeneity. In this study, we use a relatively new neuroimaging approach, atrophy network mapping, to localize clinical symptoms in patients with FTLD to specific brain networks transdiagnostically.
Data were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative and 4-Repeat Tauopathy Neuroimaging Initiative. Inclusion required T1-weighted MRI and a diagnosis of behavioral-variant frontotemporal dementia (bvFTD), semantic-variant primary progressive aphasia (svPPA), nonfluent primary progressive aphasia (nfvPPA), progressive supranuclear palsy Richardson syndrome (PSP-rs), corticobasal syndrome (CBS), or normal cognition. Measures of social cognition (Interpersonal Reactivity Index, Revised Self-Monitoring Scale), language (Boston Naming Test, Animal Fluency), and motor function (Unified Parkinson Disease Rating Scale Part III, PSP Rating Scale) were correlated with neuroimaging measures, including cortical thickness, volume, and atrophy network mapping, a newer method that localizes regions connected to brain atrophy using a functional connectome from cognitively normal persons (n = 1,000).
Fifty-seven patients with bvFTD (age 61.2 ± 6.8 years, 35% female), 41 PSP-rs (age 69.7 ± 7.4 years, 54% female), 39 CBS (age 66.2 ± 6.2 years, 51% female), 37 svPPA (age 63.0 ± 6.0 years, 46% female), and 36 nfvPPA (age 68.3 ± 7.3 years, 53% female) and 135 healthy age-matched controls (age 63.3 ± 7.4 years, 58% female) were included. Compared with atrophy alone, atrophy network mapping showed more consistent neuroimaging results across patients with the same clinical syndrome (Dice index mean 0.68 vs 0.11, paired = 263.1, = 4,452, < 0.001), more strongly explained social cognition ((1, 84) = 10.2, = 0.002) and motor symptoms ((1, 185) = 91.3, < 0.001) across different syndromes, and showed novel neuroanatomical associations, with the temporal parietal junction relating to social cognition; Wernicke area relating to language symptoms; and association sensorimotor cortex, thalamus, and cerebellum relating to motor symptoms.
Atrophy network mapping can improve understanding of brain-behavior relationships in clinically and neuroanatomically heterogeneous disorders such as FTLD.
额颞叶变性（FTLD）包括不同的临床综合征，具有不同的症状模式和神经解剖学的神经退行性变位置。然而，FTLD 在临床上具有异质性（在几个领域存在重叠症状），在神经解剖学上也具有异质性（不同患者的大脑萎缩位置不同）。传统方法难以充分解释这种异质性。在这项研究中，我们使用了一种相对较新的神经影像学方法，即萎缩网络映射，以将 FTLD 患者的临床症状定位到特定的大脑网络中，具有跨诊断的特点。
数据来自额颞叶变性神经影像学倡议和四重复 Tau 病神经影像学倡议。纳入标准需要 T1 加权 MRI 和行为变异额颞叶痴呆（bvFTD）、语义变异原发性进行性失语症（svPPA）、非流利原发性进行性失语症（nfvPPA）、进行性核上性麻痹 Richardson 综合征（PSP-rs）、皮质基底节综合征（CBS）或正常认知的诊断。社会认知（人际反应指数、修订自我监测量表）、语言（波士顿命名测试、动物流畅性）和运动功能（统一帕金森病评定量表第三部分、PSP 评定量表）的测量与神经影像学测量相关，包括皮质厚度、体积和萎缩网络映射，这是一种使用来自认知正常个体的功能连接体来定位与大脑萎缩相关区域的新方法（n = 1000）。
纳入了 57 名 bvFTD 患者（年龄 61.2 ± 6.8 岁，35%为女性）、41 名 PSP-rs 患者（年龄 69.7 ± 7.4 岁，54%为女性）、39 名 CBS 患者（年龄 66.2 ± 6.2 岁，51%为女性）、37 名 svPPA 患者（年龄 63.0 ± 6.0 岁，46%为女性）和 36 名 nfvPPA 患者（年龄 68.3 ± 7.3 岁，53%为女性）以及 135 名年龄匹配的健康对照组（年龄 63.3 ± 7.4 岁，58%为女性）。与单纯萎缩相比，萎缩网络映射在具有相同临床综合征的患者中显示出更一致的神经影像学结果（Dice 指数均值为 0.68 与 0.11，配对 = 263.1， = 4，452， < 0.001），在不同综合征中更强烈地解释社会认知（（1，84）= 10.2， = 0.002）和运动症状（（1，185）= 91.3， < 0.001），并显示出新颖的神经解剖关联，颞顶联合区与社会认知有关；Wernicke 区与语言症状有关；联合感觉运动皮层、丘脑和小脑与运动症状有关。
萎缩网络映射可以改善对额颞叶变性等临床上和神经解剖学上具有异质性的疾病的大脑-行为关系的理解。
