The agrammatic variant of primary progressive aphasia affects normal grammatical language production, often occurs with apraxia of speech, and is associated with left frontal abnormalities on cross-sectional neuroimaging studies. We aimed to perform a detailed assessment of longitudinal change on structural and molecular neuroimaging to provide a complete picture of neurodegeneration in these patients, and to determine how patterns of progression compare to patients with isolated apraxia of speech (primary progressive apraxia of speech). We assessed longitudinal structural MRI, diffusion tensor imaging and ¹⁸F-fluorodeoxyglucose PET in 11 agrammatic aphasia subjects, 20 primary progressive apraxia of speech subjects, and 62 age and gender-matched controls with two serial assessments. Rates of change in grey matter volume and hypometabolism, and white matter fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were assessed at the voxel-level and for numerous regions of interest. The greatest rates of grey matter atrophy in agrammatic aphasia were observed in inferior, middle, and superior frontal gyri, premotor and motor cortices, as well as medial temporal lobe, insula, basal ganglia, and brainstem compared to controls. Longitudinal decline in metabolism was observed in the same regions, with additional findings in medial and lateral parietal lobe. Diffusion tensor imaging changes were prominent bilaterally in inferior and middle frontal white matter and superior longitudinal fasciculus, as well as right inferior fronto-occipital fasciculus, superior frontal and precentral white matter. More focal patterns of degeneration of motor and premotor cortex were observed in primary progressive apraxia of speech. Agrammatic aphasia showed greater rates of grey matter atrophy, decline in metabolism, and white matter degeneration compared to primary progressive apraxia of speech in the left frontal lobe, predominantly inferior and middle frontal grey and white matter. Correlations were also assessed between rates of change on neuroimaging and rates of clinical decline. Progression of aphasia correlated with rates of degeneration in frontal and temporal regions within the language network, while progression of parkinsonism and limb apraxia correlated with degeneration of motor cortex and brainstem. These findings demonstrate that disease progression in agrammatic aphasia is associated with widespread neurodegeneration throughout regions of the language network, as well as connecting white matter tracts, but also with progression to regions outside of the language network that are responsible for the development of motor symptoms. The fact that patterns of progression differed from primary progressive apraxia of speech supports the clinical distinction of these syndromes.

中文翻译：

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语法性原发性进行性失语症的纵向结构和分子神经影像学检查

原发性进行性失语症的语法变异会影响正常的语法语言产生，通常伴有语言失语，并且在横断面神经影像学研究中与左额叶异常有关。我们旨在对结构和分子神经影像学的纵向变化进行详细的评估，以提供这些患者神经退行性病变的完整图片，并确定与孤立性语言失用（原发性进行性语言失用）患者相比，其发展方式如何。我们评估了纵向结构MRI，弥散张量成像和¹⁸F-氟脱氧葡萄糖PET在11位语法失语症患者，20位原发性进行性失语症患者以及62位年龄和性别匹配的对照组中进行了两次系列评估。在体素水平和许多感兴趣的区域评估了灰质体积和低代谢，白质分数各向异性，平均扩散率，径向扩散率和轴向扩散率的变化率。与对照组相比，在下，中和上额回回，运动前和运动皮层以及颞中叶，岛突，基底神经节和脑干中观察到语法失语的灰质萎缩发生率最高。在相同区域观察到新陈代谢的纵向下降，在内侧和外侧顶叶中发现了更多的发现。扩散张量成像变化在额中下额中部白质和上纵筋膜以及右额额枕下筋膜，额中部和中央前白质中双侧均显着。在原发性进行性语言失用中观察到更多的运动和皮层退化的局灶性模式。与左额叶的主要言语进行性失语症相比，语法失语症显示灰质萎缩，代谢下降和白质变性的发生率更高，主要是下额和中额灰质和白质。还评估了神经影像学变化率与临床下降率之间的相关性。失语症的进展与语言网络中额叶和颞叶变性的发生率相关，而帕金森氏症和肢体失用的进展与运动皮层和脑干的退化有关。这些发现表明，语法失语症的疾病进展与整个语言网络区域中广泛的神经退行性变以及与白质束的连接有关，而且还与语言网络外部负责运动症状发展的区域发展有关。进展模式不同于原发性进行性语言失用的事实支持了这些综合征的临床区别。以及将白质束连接起来，而且还会发展到语言网络之外负责运动症状发展的区域。进展模式不同于原发性进行性语言失用的事实支持了这些综合征的临床区别。以及将白质束连接起来，而且还会发展到语言网络之外负责运动症状发展的区域。进展模式不同于原发性进行性语言失用的事实支持了这些综合征的临床区别。