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Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia

Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degener...

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Autores principales: Ramanan, Siddharth, El-Omar, Hashim, Roquet, Daniel, Ahmed, Rebekah M, Hodges, John R, Piguet, Olivier, Lambon Ralph, Matthew A, Irish, Muireann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847565/
https://www.ncbi.nlm.nih.gov/pubmed/36687395
http://dx.doi.org/10.1093/braincomms/fcac344
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author Ramanan, Siddharth
El-Omar, Hashim
Roquet, Daniel
Ahmed, Rebekah M
Hodges, John R
Piguet, Olivier
Lambon Ralph, Matthew A
Irish, Muireann
author_facet Ramanan, Siddharth
El-Omar, Hashim
Roquet, Daniel
Ahmed, Rebekah M
Hodges, John R
Piguet, Olivier
Lambon Ralph, Matthew A
Irish, Muireann
author_sort Ramanan, Siddharth
collection PubMed
description Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entities, mounting evidence indicates overlapping cognitive–behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive–behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive–behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked individual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive–behavioural overlap (i) occurs systematically in frontotemporal dementia; (ii) varies in a graded manner between individuals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive–behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes.
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spelling pubmed-98475652023-01-20 Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia Ramanan, Siddharth El-Omar, Hashim Roquet, Daniel Ahmed, Rebekah M Hodges, John R Piguet, Olivier Lambon Ralph, Matthew A Irish, Muireann Brain Commun Original Article Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entities, mounting evidence indicates overlapping cognitive–behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive–behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive–behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked individual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive–behavioural overlap (i) occurs systematically in frontotemporal dementia; (ii) varies in a graded manner between individuals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive–behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes. Oxford University Press 2023-01-05 /pmc/articles/PMC9847565/ /pubmed/36687395 http://dx.doi.org/10.1093/braincomms/fcac344 Text en © The Author(s) 2023. 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
Ramanan, Siddharth
El-Omar, Hashim
Roquet, Daniel
Ahmed, Rebekah M
Hodges, John R
Piguet, Olivier
Lambon Ralph, Matthew A
Irish, Muireann
Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title_full Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title_fullStr Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title_full_unstemmed Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title_short Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
title_sort mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847565/
https://www.ncbi.nlm.nih.gov/pubmed/36687395
http://dx.doi.org/10.1093/braincomms/fcac344
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