Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia

Abstract Background Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network rela...

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Main Authors: Adeline Su Lyn Ng, Juan Wang, Kwun Kei Ng, Joanna Su Xian Chong, Xing Qian, Joseph Kai Wei Lim, Yi Jayne Tan, Alisa Cui Wen Yong, Russell Jude Chander, Shahul Hameed, Simon Kang Seng Ting, Nagaendran Kandiah, Juan Helen Zhou
Format: Article
Language:English
Published: BMC 2021-01-01
Series:Alzheimer’s Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13195-020-00752-w
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spelling doaj-4d4cc932afde4537a28a9a7f12d1ea6d2021-01-10T12:54:56ZengBMCAlzheimer’s Research & Therapy1758-91932021-01-0113111610.1186/s13195-020-00752-wDistinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementiaAdeline Su Lyn Ng0Juan Wang1Kwun Kei Ng2Joanna Su Xian Chong3Xing Qian4Joseph Kai Wei Lim5Yi Jayne Tan6Alisa Cui Wen Yong7Russell Jude Chander8Shahul Hameed9Simon Kang Seng Ting10Nagaendran Kandiah11Juan Helen Zhou12Department of Neurology, National Neuroscience Institute, Tan Tock Seng HospitalCentre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Neurology, National Neuroscience Institute, Tan Tock Seng HospitalDepartment of Neurology, National Neuroscience Institute, Tan Tock Seng HospitalDepartment of Neurology, National Neuroscience Institute, Tan Tock Seng HospitalNeuroscience and Behavioral Disorders Program, Duke-NUS Medical SchoolNeuroscience and Behavioral Disorders Program, Duke-NUS Medical SchoolDepartment of Neurology, National Neuroscience Institute, Tan Tock Seng HospitalNeuroscience and Behavioral Disorders Program, Duke-NUS Medical SchoolAbstract Background Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits. Methods In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. Results Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. Conclusions Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.https://doi.org/10.1186/s13195-020-00752-wAlzheimer’s disease (AD)Behavioral variant frontotemporal dementia (bvFTD)Higher-order cognitive networksNetwork distinctivenessNetwork segregation and integration
collection DOAJ
language English
format Article
sources DOAJ
author Adeline Su Lyn Ng
Juan Wang
Kwun Kei Ng
Joanna Su Xian Chong
Xing Qian
Joseph Kai Wei Lim
Yi Jayne Tan
Alisa Cui Wen Yong
Russell Jude Chander
Shahul Hameed
Simon Kang Seng Ting
Nagaendran Kandiah
Juan Helen Zhou
spellingShingle Adeline Su Lyn Ng
Juan Wang
Kwun Kei Ng
Joanna Su Xian Chong
Xing Qian
Joseph Kai Wei Lim
Yi Jayne Tan
Alisa Cui Wen Yong
Russell Jude Chander
Shahul Hameed
Simon Kang Seng Ting
Nagaendran Kandiah
Juan Helen Zhou
Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
Alzheimer’s Research & Therapy
Alzheimer’s disease (AD)
Behavioral variant frontotemporal dementia (bvFTD)
Higher-order cognitive networks
Network distinctiveness
Network segregation and integration
author_facet Adeline Su Lyn Ng
Juan Wang
Kwun Kei Ng
Joanna Su Xian Chong
Xing Qian
Joseph Kai Wei Lim
Yi Jayne Tan
Alisa Cui Wen Yong
Russell Jude Chander
Shahul Hameed
Simon Kang Seng Ting
Nagaendran Kandiah
Juan Helen Zhou
author_sort Adeline Su Lyn Ng
title Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
title_short Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
title_full Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
title_fullStr Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
title_full_unstemmed Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
title_sort distinct network topology in alzheimer’s disease and behavioral variant frontotemporal dementia
publisher BMC
series Alzheimer’s Research & Therapy
issn 1758-9193
publishDate 2021-01-01
description Abstract Background Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits. Methods In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. Results Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. Conclusions Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.
topic Alzheimer’s disease (AD)
Behavioral variant frontotemporal dementia (bvFTD)
Higher-order cognitive networks
Network distinctiveness
Network segregation and integration
url https://doi.org/10.1186/s13195-020-00752-w
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