TY - JOUR
T1 - Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum
AU - Pizzarotti, Beatrice
AU - Palesi, Fulvia
AU - Vitali, Paolo
AU - Castellazzi, Gloria
AU - Anzalone, Nicoletta
AU - Alvisi, Elena
AU - Martinelli, Daniele
AU - Bernini, Sara
AU - Cotta Ramusino, Matteo
AU - Ceroni, Mauro
AU - Micieli, Giuseppe
AU - Sinforiani, Elena
AU - D’Angelo, Egidio
AU - Costa, Alfredo
AU - Gandini Wheeler-Kingshott, Claudia A.M.
N1 - Funding Information:
We thank the patients, their families, all healthy volunteers for making this research possible. We thank Giancarlo Germani for MRI acquisitions and Roberta Fortunato for her support to the study organization. Funding. This work was performed at the IRCCS Mondino Foundation and was supported by the Italian Ministry of Health (RC2014?2017). FP and ED?A received funding from the European Union?s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) and No. 945539 (Human Brain Project SGA3). The United States Multiple Sclerosis Society and UCL-UCLH Biomedical Research Centre for ongoing support of the Queen Square MS Centre (CGWK). CGWK receives funding from ISRT, Wings for Life, and the Craig H. Neilsen Foundation (the INSPIRED study), from the MS Society (#77), Wings for Life (#169111), and Horizon2020 (CDS-QUAMRI, #634541).
Funding Information:
This work was performed at the IRCCS Mondino Foundation and was supported by the Italian Ministry of Health (RC2014– 2017). FP and ED’A received funding from the European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) and No. 945539 (Human Brain Project SGA3). The United States Multiple Sclerosis Society and UCL-UCLH Biomedical Research Centre for ongoing support of the Queen Square MS Centre (CGWK). CGWK receives funding from ISRT, Wings for Life, and the Craig H. Neilsen Foundation (the INSPIRED study), from the MS Society (#77), Wings for Life (#169111), and Horizon2020 (CDS-QUAMRI, #634541).
Publisher Copyright:
© Copyright © 2020 Pizzarotti, Palesi, Vitali, Castellazzi, Anzalone, Alvisi, Martinelli, Bernini, Cotta Ramusino, Ceroni, Micieli, Sinforiani, D’Angelo, Costa and Gandini Wheeler-Kingshott.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/26
Y1 - 2020/11/26
N2 - Background: Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understand this clinical continuum. Methods: We used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness ((Formula presented.)) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency, and semantic fluency. Results: Common (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS, and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g., a difference of cerebral and cerebellar involvement between FTSD and ALS). (Formula presented.) values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and (Formula presented.) in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions. Conclusion: We identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.
AB - Background: Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understand this clinical continuum. Methods: We used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness ((Formula presented.)) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency, and semantic fluency. Results: Common (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS, and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g., a difference of cerebral and cerebellar involvement between FTSD and ALS). (Formula presented.) values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and (Formula presented.) in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions. Conclusion: We identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.
KW - ALS
KW - cerebellum
KW - dementia
KW - FTD
KW - FTD-ALS continuum
KW - VBM
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U2 - 10.3389/fnagi.2020.593526
DO - 10.3389/fnagi.2020.593526
M3 - Article
AN - SCOPUS:85097503427
VL - 12
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
M1 - 593526
ER -