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首页> 外文期刊>Alzheimer s Research & Therapy >Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales
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Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales

机译：视觉评分量表揭示的遗传额颞叶痴呆倡议（GENFI）队列中脑萎缩的不同模式

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In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. We used visual rating scales to investigate whether identifying atrophy in these areas may be helpful in distinguishing symptomatic patients carrying different causal mutations in the microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame (C9ORF72) genes. We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms. Magnetic resonance imaging of 343 subjects (63 symptomatic mutation carriers, 132 presymptomatic mutation carriers and 148 control subjects) from the Genetic Frontotemporal Dementia Initiative study were analysed by two trained raters using a protocol of six visual rating scales that identified atrophy in key regions of the brain (orbitofrontal, anterior cingulate, frontoinsula, anterior and medial temporal lobes and posterior cortical areas). Intra- and interrater agreement were greater than 0.73 for all the scales. Voxel-based morphometric analysis demonstrated a strong correlation between the visual rating scale scores and grey matter atrophy in the same region for each of the scales. Typical patterns of atrophy were identified: symmetric anterior and medial temporal lobe involvement for MAPT, asymmetric frontal and parietal loss for GRN, and a more widespread pattern for C9ORF72. Presymptomatic MAPT carriers showed greater atrophy in the medial temporal region than control subjects, but the visual rating scales could not identify presymptomatic atrophy in GRN or C9ORF72 carriers. These simple-to-use and reproducible scales may be useful tools in the clinical setting for the discrimination of different mutations of frontotemporal dementia, and they may even help to identify atrophy prior to onset in those with MAPT mutations.
机译：在额颞叶性痴呆患者中，研究表明脑萎缩最早发生在前扣带状，岛状和额叶。我们使用视觉评分量表调查了在这些区域鉴定萎缩是否有助于区分症状患者，这些患者在微管相关蛋白tau（MAPT），progranulin（GRN）和9号染色体开放阅读框（C9ORF72）基因中携带不同的因果突变。我们还分析了无症状携带者，以查看是否有可能在症状出现之前通过视觉识别脑萎缩。两名颞叶痴呆症倡议组织研究的343名受试者（63名有症状的突变携带者，132名症状前的突变携带者和148名对照受试者）的磁共振成像由两名训练有素的评估者进行了分析，使用六种视觉评级量表确定了关键部位的萎缩。大脑（眶额，前扣带回，额窦，颞前叶和内侧颞叶以及后皮质区域）。所有尺度的内部和内部一致性均大于0.73。基于体素的形态计量学分析表明，每种等级在同一区域的视觉等级量表得分与灰质萎缩之间存在很强的相关性。确定了典型的萎缩模式：MAPT涉及对称的前颞叶内侧颞叶，GRN的对称性额叶和顶叶缺失以及C9ORF72的分布更为广泛。有症状的MAPT携带者在内侧颞区比对照组有更大的萎缩，但是视觉评分量表无法识别出GRN或C9ORF72携带者的有症状的萎缩。这些易于使用且可重现的量表在临床上可用于区分额颞叶痴呆的不同突变，甚至可能有助于在患有MAPT突变的患者中在发病前鉴定萎缩。

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