Distinct network topology in Alzheimer\u2019s disease and behavioral variant frontotemporal dementia

Adeline Su Lyn Ng,Juan Helen Zhou,Joseph Kai Wei Lim,Nagaendran Kandiah,Shahul Hameed,Juan Wang,Xing Qian,Russell Jude Chander,Yi Jayne Tan,Simon Kang Seng Ting,Alisa Cui Wen Yong,Kwun Kei Ng,Joanna Su Xian Chong

doi:10.1186/s13195-020-00752-w

Abstract

BackgroundAlzheimer’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.MethodsIn 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.ResultsOur 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.ConclusionsOur findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.

Highlights

Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively
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
AD and behavioral variant frontotemporal dementia (bvFTD) were comparable in education, Clinical Dementia Rating (CDR), MMSE/ Montreal Cognitive Assessment (MoCA)

Summary

Introduction

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 altered and underpin cognitive and social–emotional functional deficits. Charting the convergence and divergence in the alterations of brain network-based metrics caused by these dementia subtypes could help improve imaging marker sensitivity for differential diagnosis and symptoms mapping [9, 66, 72, 118]

Methods

Results

Conclusion