Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales

Giorgio G Fumagalli, Paola Basilico, Andrea Arighi, Martina Bocchetta, Katrina M Dick, David M Cash, Sophie Harding, Matteo Mercurio, Chiara Fenoglio, Anna M Pietroboni, Laura Ghezzi, John van Swieten, Barbara Borroni, Alexandre de Mendonça, Mario Masellis, Maria C Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni B FrisoniRobert Laforce, Elizabeth Finger, Sandro Sorbi, Elio Scarpini, Jonathan D Rohrer, Daniela Galimberti, Genetic FTD Initiative (GENFI)

Research output: Contribution to journalArticle

Abstract

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 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.

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 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.

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.

Original languageEnglish
Pages (from-to)46
JournalAlzheimer's Research and Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - May 24 2018

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Frontotemporal Dementia
Atrophy
Brain
Microtubule-Associated Proteins
Temporal Lobe
Mutation
Gyrus Cinguli
Chromosomes, Human, Pair 9
Frontal Lobe
Prefrontal Cortex
Open Reading Frames
Magnetic Resonance Imaging

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Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales. / Fumagalli, Giorgio G; Basilico, Paola; Arighi, Andrea; Bocchetta, Martina; Dick, Katrina M; Cash, David M; Harding, Sophie; Mercurio, Matteo; Fenoglio, Chiara; Pietroboni, Anna M; Ghezzi, Laura; van Swieten, John; Borroni, Barbara; de Mendonça, Alexandre; Masellis, Mario; Tartaglia, Maria C; Rowe, James B; Graff, Caroline; Tagliavini, Fabrizio; Frisoni, Giovanni B; Laforce, Robert; Finger, Elizabeth; Sorbi, Sandro; Scarpini, Elio; Rohrer, Jonathan D; Galimberti, Daniela; Genetic FTD Initiative (GENFI).

In: Alzheimer's Research and Therapy, Vol. 10, No. 1, 24.05.2018, p. 46.

Research output: Contribution to journalArticle

Fumagalli, GG, Basilico, P, Arighi, A, Bocchetta, M, Dick, KM, Cash, DM, Harding, S, Mercurio, M, Fenoglio, C, Pietroboni, AM, Ghezzi, L, van Swieten, J, Borroni, B, de Mendonça, A, Masellis, M, Tartaglia, MC, Rowe, JB, Graff, C, Tagliavini, F, Frisoni, GB, Laforce, R, Finger, E, Sorbi, S, Scarpini, E, Rohrer, JD, Galimberti, D & Genetic FTD Initiative (GENFI) 2018, 'Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales', Alzheimer's Research and Therapy, vol. 10, no. 1, pp. 46. https://doi.org/10.1186/s13195-018-0376-9
Fumagalli, Giorgio G ; Basilico, Paola ; Arighi, Andrea ; Bocchetta, Martina ; Dick, Katrina M ; Cash, David M ; Harding, Sophie ; Mercurio, Matteo ; Fenoglio, Chiara ; Pietroboni, Anna M ; Ghezzi, Laura ; van Swieten, John ; Borroni, Barbara ; de Mendonça, Alexandre ; Masellis, Mario ; Tartaglia, Maria C ; Rowe, James B ; Graff, Caroline ; Tagliavini, Fabrizio ; Frisoni, Giovanni B ; Laforce, Robert ; Finger, Elizabeth ; Sorbi, Sandro ; Scarpini, Elio ; Rohrer, Jonathan D ; Galimberti, Daniela ; Genetic FTD Initiative (GENFI). / Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales. In: Alzheimer's Research and Therapy. 2018 ; Vol. 10, No. 1. pp. 46.
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abstract = "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 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.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 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.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.",
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T1 - Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales

AU - Fumagalli, Giorgio G

AU - Basilico, Paola

AU - Arighi, Andrea

AU - Bocchetta, Martina

AU - Dick, Katrina M

AU - Cash, David M

AU - Harding, Sophie

AU - Mercurio, Matteo

AU - Fenoglio, Chiara

AU - Pietroboni, Anna M

AU - Ghezzi, Laura

AU - van Swieten, John

AU - Borroni, Barbara

AU - de Mendonça, Alexandre

AU - Masellis, Mario

AU - Tartaglia, Maria C

AU - Rowe, James B

AU - Graff, Caroline

AU - Tagliavini, Fabrizio

AU - Frisoni, Giovanni B

AU - Laforce, Robert

AU - Finger, Elizabeth

AU - Sorbi, Sandro

AU - Scarpini, Elio

AU - Rohrer, Jonathan D

AU - Galimberti, Daniela

AU - Genetic FTD Initiative (GENFI)

PY - 2018/5/24

Y1 - 2018/5/24

N2 - 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 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.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 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.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.

AB - 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 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.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 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.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.

U2 - 10.1186/s13195-018-0376-9

DO - 10.1186/s13195-018-0376-9

M3 - Article

C2 - 29793546

VL - 10

SP - 46

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

SN - 1758-9193

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