Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales
Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales
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DOI：
10.1186/s13195-018-0376-9
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发表时间：
2018-05-24
影响因子：
9
通讯作者：
Galimberti, Daniela
中科院分区：
文献类型：
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作者：
Fumagalli, Giorgio G.;Basilico, Paola;Galimberti, Daniela
背景：在额颞叶痴呆患者中，脑萎缩最早发生在前扣带回、岛叶和额叶。我们使用视觉评定量表来研究这些区域的萎缩是否有助于区分携带不同原因突变的微管相关蛋白tau(MAPT)、原颗粒(GRN)和9号染色体开放前导框架(C90RP72)基因的症状性患者。我们还对无症状携带者进行了分析，以了解在症状出现之前是否有可能从视觉上识别脑萎缩。方法：343例受试者(63例症状性突变携带者，来自遗传性额颞叶痴呆倡议研究的132名症状前突变携带者和148名对照受试者由两名训练有素的评分员使用6个视觉评分表进行分析，这些评分表识别大脑关键区域(眶前区、扣带前区、额岛区、前内侧颞叶和后部皮质区)的萎缩。结果：所有评分者内部和评价者间的一致性均大于0.73。基于体素的形态计量学分析表明，视觉分级量表得分与同一区域的灰质萎缩之间存在很强的相关性，在每一种尺度上，典型的萎缩模式被识别出来：MAPT的对称性前额叶和内侧颞叶受累，GRN的额叶和顶叶不对称的丧失，以及更广泛的C9ORF72模式。症状前MAPT携带者在内侧颞区的萎缩程度明显高于对照组，但视觉评定量表不能识别GRN或C9ORF72携带者的症状前萎缩。结论：这些简单易用、重复性好的量表可作为临床区分额颞部痴呆不同突变的有用工具，甚至有助于识别MAPT突变者的发病前萎缩。
Background: 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 leading frame (C90RP72) genes We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms.Methods: 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).Results: intra and interrater agreement were greater than 0.73 for all the scales. Voxel-based morphometnc 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 fot GRN, and a more widespread pattern foi 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.Conclusions: 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.