Abstract
BackgroundIn 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.MethodsMagnetic 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).ResultsIntra- 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.ConclusionsThese 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.
Highlights
In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes
Previous studies have shown that each mutation has a distinct pattern of atrophy: Mutations in microtubule-associated protein tau (MAPT) have been associated with atrophy predominantly in the anteromedial temporal lobes [6, 7], whereas mutations in GRN are associated with an asymmetric pattern of atrophy that involves the frontal, temporal and parietal lobes [6, 8]; chromosome 9 open reading frame 72 (C9ORF72) mutation carriers have relatively widespread cortical atrophy, including posterior areas [1, 9, 10]
Participants Subjects were recruited from the Genetic Frontotemporal Dementia Initiative (GENFI) study, which in the first phase consisted of 13 centres in the United Kingdom, Canada, Italy, The Netherlands, Sweden and Portugal
Summary
In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. Previous studies have shown that each mutation has a distinct pattern of atrophy: Mutations in MAPT have been associated with atrophy predominantly in the anteromedial temporal lobes [6, 7], whereas mutations in GRN are associated with an asymmetric pattern of atrophy that involves the frontal, temporal and parietal lobes [6, 8]; C9ORF72 mutation carriers have relatively widespread cortical atrophy, including posterior areas [1, 9, 10] Such studies have relied on volumetric ROIs or voxel-wise analyses that are difficult to translate into routine clinical practice, where visual evaluation remains the primary diagnostic method [11]. The objective of the present study was to determine specific visual patterns of atrophy in genetic FTD, in both symptomatic and presymptomatic mutation carriers, and in all three of the major genetic forms: GRN, MAPT and C9ORF72
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
