Title :

Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort

Author(s) :

Bocchetta, Martina [Auteur]
Todd, Emily G [Auteur]
Bouzigues, Arabella [Auteur]
Cash, David M. [Auteur]
Nicholas, Jennifer M [Auteur]
Convery, Rhian S. [Auteur]
Russell, Lucy L. [Auteur]
Thomas, David L [Auteur]
Malone, Ian B [Auteur]
Iglesias, Juan Eugenio [Auteur]
Van Swieten, John C. [Auteur]
Jiskoot, Lize C [Auteur]
Seelaar, Harro [Auteur]
Borroni, Barbara [Auteur]
Galimberti, Daniela [Auteur]
Sanchez-Valle, Raquel [Auteur]
Laforce, Robert [Auteur]
Moreno, Fermin [Auteur]
Synofzik, Matthis [Auteur]
Graff, Caroline [Auteur]
Masellis, Mario [Auteur]
Tartaglia, Maria Carmela [Auteur]
Rowe, James B. [Auteur]
Vandenberghe, Rik [Auteur]
Finger, Elizabeth [Auteur]
Tagliavini, Fabrizio [Auteur]
De Mendonça, Alexandre [Auteur]
Santana, Isabel [Auteur]
Butler, Chris R. [Auteur]
Ducharme, Simon [Auteur]
Gerhard, Alexander [Auteur]
Danek, Adrian [Auteur]
Levin, Johannes [Auteur]
Otto, Markus [Auteur]
Sorbi, Sandro [Auteur]
Le Ber, Isabelle [Auteur]
Pasquier, Florence [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Rohrer, Jonathan D. [Auteur]

Journal title :

Brain Communications

Abbreviated title :

Brain Commun

Volume number :

5

Pages :

fcad061

Publisher :

Oxford University Press on behalf of the Guarantors of Brain

Publication date :

2023-03-10

ISSN :

2632-1297

English keyword(s) :

genetic frontotemporal dementia
MRI imaging
brain volumetry
diffusion imaging
presymptomatic stage

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]

English abstract : [en]

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated ...
Show more >Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as ‘normal’ or ‘abnormal’ based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the ‘normal’ and ‘abnormal’ groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

Building Next-Generation Computational Tools for High Resolution Neuroimaging Studies
Neurodegenerative Disease Research (JPND)

ANR Project :

Bordeaux Region Aquitaine Initiative for Neuroscience
Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Troubles cognitifs dégénératifs et vasculaires

Submission date :

2024-01-15T23:17:20Z
2024-11-29T10:50:26Z