Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Alzheimers Res Ther. 2022 Feb 9;14(1):27. doi: 10.1186/s13195-022-00974-0.
Cortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).
In this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.
The comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.
Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.
皮质平均扩散率是一种新的成像指标，对神经退行性综合征的早期变化敏感。较高的皮质平均扩散率值反映了微观结构的紊乱，并被提出作为一种敏感的生物标志物，可能早于宏观的皮质变化。我们旨在检验皮质平均扩散率比皮质厚度更能检测原发性进行性失语症（PPA）的皮质变化的假设。
在这项多中心病例对照研究中，我们从三个中心招募了 120 名 PPA 患者（52 名非流利型、31 名语义型和 32 名失语法型；和 5 名 GRN 相关的 PPA）以及 89 名对照者。3T MRI 方案包括结构和弥散加权序列。使用临床痴呆评定量表评估疾病严重程度。使用基于表面的方法计算皮质厚度和皮质平均扩散率。
每种 PPA 变体与对照组之间的比较显示，皮质平均扩散率增加和皮质变薄在重叠区域，反映了每种变体的神经退行性变的典型部位。重要的是，皮质平均扩散率的增加也扩展到其他与 PPA 相关的区域，并与所有 PPA 组的疾病严重程度相关。当仅观察到最小的皮质变薄时，非常轻度的 PPA 患者的皮质平均扩散率也增加，并且与疾病严重程度的测量值具有良好的相关性。
皮质平均扩散率作为研究 PPA 中神经退行性变相关微观结构变化的敏感生物标志物具有潜力。
