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 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.

Cognitive Improvement Via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Alzheimer’s Disease Spectrum Patients

“…It's worth noting that the potential effect of rTMS spread from directly targeted areas to anatomically areas, which provides an opportunity to apply rTMS at one point of neural circuit [54]. And, previous graph theoretical analysis in functional network showed that AD patients had higher degree centrality and nodal e ciency in thalamus [34]. These ndings were consistent to our results.…”

“…(i) Post-wise differences correlation: It should be noted that the improved white matter integrity of right Thalamic Radiation were observed after four-week neuro-navigated rTMS treatment. Among MCI group, the increased white matter integrity of posterior portion of the right Thalamic Radiation's (nodes 88-94) correlated positively with the improved episodic memory (r = 0.585, p = 0.028) and improved language function (r = 0.663, p = 0.007) (ii) Theoretical parameter correlation: previous studies demonstrated that compared to healthy control, AD patients showed higher degree centrality and nodal e ciency in thalamus [34]. We thought that network attributes of the thalamus were improved after the intervention.…”

Disrupted coupling between salience network segregation and glucose metabolism is associated with cognitive decline in Alzheimer's disease – A simultaneous resting-state FDG-PET/fMRI study

“…Following the similar approach of segregation calculation as in our work, recent studies showed significant reduced segregations in the global system and the episodic memory networks in patients with AD ( Cassady et al, 2021 , Ewers et al, 2021 ). Using various other measures of segregation such as clustering coefficient or within-module degree, decreased segregation has been reported in the whole brain and multiple networks in patients with MCI and AD ( Brier et al, 2014 , Contreras et al, 2019 , Costumero et al, 2020 , Dai et al, 2019 , Ng et al, 2021 , Tumati et al, 2020 ). Together, these results indicate that the distinct and functionally specialized role of individual network seemed to be blurred in the brain functional organization of MCI and AD.…”

The Role of Graph Theory in Evaluating Brain Network Alterations in Frontotemporal Dementia

“…More recently, several studies have applied advanced MRI acquisitions and analyses to obtain an in-depth characterization of brain alterations with respect to the simple gray matter atrophy. Particularly, an increasing number of studies have assessed brain connectivity through graph-theoretical methods, highlighting that this approach shows unique potentialities in FTD (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”