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Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia

The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distr...

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Autores principales: Vuksanović, Vesna, Staff, Roger T, Morson, Suzannah, Ahearn, Trevor, Bracoud, Luc, Murray, Alison D, Bentham, Peter, Kipps, Christopher M, Harrington, Charles R, Wischik, Claude M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688778/
https://www.ncbi.nlm.nih.gov/pubmed/34939031
http://dx.doi.org/10.1093/braincomms/fcab241
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author Vuksanović, Vesna
Staff, Roger T
Morson, Suzannah
Ahearn, Trevor
Bracoud, Luc
Murray, Alison D
Bentham, Peter
Kipps, Christopher M
Harrington, Charles R
Wischik, Claude M
author_facet Vuksanović, Vesna
Staff, Roger T
Morson, Suzannah
Ahearn, Trevor
Bracoud, Luc
Murray, Alison D
Bentham, Peter
Kipps, Christopher M
Harrington, Charles R
Wischik, Claude M
author_sort Vuksanović, Vesna
collection PubMed
description The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke’s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.
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spelling pubmed-86887782021-12-21 Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia Vuksanović, Vesna Staff, Roger T Morson, Suzannah Ahearn, Trevor Bracoud, Luc Murray, Alison D Bentham, Peter Kipps, Christopher M Harrington, Charles R Wischik, Claude M Brain Commun Original Article The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke’s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome. Oxford University Press 2021-10-21 /pmc/articles/PMC8688778/ /pubmed/34939031 http://dx.doi.org/10.1093/braincomms/fcab241 Text en © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Vuksanović, Vesna
Staff, Roger T
Morson, Suzannah
Ahearn, Trevor
Bracoud, Luc
Murray, Alison D
Bentham, Peter
Kipps, Christopher M
Harrington, Charles R
Wischik, Claude M
Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_full Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_fullStr Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_full_unstemmed Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_short Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_sort degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688778/
https://www.ncbi.nlm.nih.gov/pubmed/34939031
http://dx.doi.org/10.1093/braincomms/fcab241
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