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Data-driven staging of genetic frontotemporal dementia using multi-modal MRI.

Published version
Peer-reviewed

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Authors

Sanchez-Valle, Raquel 
Moreno, Fermin 
Laforce, Robert 

Abstract

Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrastive trajectory inference (cTI), an unsupervised machine learning algorithm that analyzes temporal patterns in high-dimensional large-scale population datasets to obtain individual scores of disease stage. We used cross-sectional MRI data (gray matter density, T1/T2 ratio as a proxy for myelin content, resting-state functional amplitude, gray matter fractional anisotropy, and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) and a control group of 253 noncarriers in the Genetic Frontotemporal Dementia Initiative. We compared the cTI-obtained disease scores to the estimated years to onset (age-mean age of onset in relatives), clinical, and neuropsychological test scores. The cTI based disease scores were correlated with all clinical and neuropsychological tests (measuring behavioral symptoms, attention, memory, language, and executive functions), with the highest contribution coming from mean diffusivity. Mean cTI scores were higher in the presymptomatic carriers than controls, indicating that the method may capture subtle pre-dementia cerebral changes, although this change was not replicated in a subset of subjects with complete data. This study provides a proof of concept that cTI can identify data-driven disease stages in a heterogeneous sample combining different mutations and disease stages of genetic FTD using only MRI metrics.

Description

Funder: Fondation Brain Canada; Id: http://dx.doi.org/10.13039/100009408


Funder: Fonds de Recherche du Québec ‐ Santé; Id: http://dx.doi.org/10.13039/501100000156


Funder: Health Canada; Id: http://dx.doi.org/10.13039/501100000008


Funder: Brain Canada Foundation; Id: http://dx.doi.org/10.13039/100009408

Keywords

disease progression, frontotemporal dementia, magnetic resonance imaging, unsupervised machine learning, Cross-Sectional Studies, Frontotemporal Dementia, Heterozygote, Humans, Language, Magnetic Resonance Imaging

Journal Title

Hum Brain Mapp

Conference Name

Journal ISSN

1065-9471
1097-0193

Volume Title

Publisher

Wiley
Sponsorship
Medical Research Council (MR/J009482/1)
Medical Research Council (MR/M008983/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MC_UU_00005/12)