Adeline Su Lyn Ng1,2, Juan Wang3, Kwun Kei Ng3, Joanna Su Xian Chong3, Xing Qian3, Joseph Kai Wei Lim3, Yi Jayne Tan1,2, Alisa Cui Wen Yong1, Russell Jude Chander1, Shahul Hameed2,4, Simon Kang Seng Ting2,4, Nagaendran Kandiah1,2, Juan Helen Zhou5,6,7. 1. Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore. 2. Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore, Singapore. 3. Centre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 4. Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore. 5. Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore, Singapore. helen.zhou@nus.edu.sg. 6. Centre for Sleep and Cognition, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. helen.zhou@nus.edu.sg. 7. Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. helen.zhou@nus.edu.sg.
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.
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.
Authors: Joanna Su Xian Chong; Hyemin Jang; Hee Jin Kim; Kwun Kei Ng; Duk L Na; Jae Hong Lee; Sang Won Seo; Juan Zhou Journal: Neurology Date: 2019-09-11 Impact factor: 9.910
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