Functional segregation loss over time is moderated by <i>APOE</i> genotype in healthy elderly

Ng, Kwun Kei; Qiu, Yingwei; Lo, June C.; Koay, Evelyn Siew-Chuan; Koh, Woon‐Puay; Chee, Michael W.L.; Zhou, Juan

doi:10.1002/hbm.24036

Cited by 18 publications

(14 citation statements)

References 80 publications

(113 reference statements)

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“…In addition, compared to bvFTD, AD patients showed higher participation coefficient, a measure of inter-network connectedness, in many referent CN regions, suggestive of a loss of segregation between the DN and CN in AD. Loss of DN and CN distinctiveness may reflect declining network functional specialization or processing efficiency commonly observed in normal aging [ 24 , 26 ], which might be accelerated by AD risk factors such as the possession of APOE e4 gene [ 80 ]. Together, these module-based findings complement our nodal FC results to highlight the putative reciprocal relationship between the DN and SVAN when these networks are compromised by dementia pathologies.…”

Section: Discussionmentioning

confidence: 99%

“…Both functional and structural images were preprocessed using a standard pipeline based on FMRIB Software Library (FSL) [ 60 ] and Analysis of Functional NeuroImages software (AFNI) [ 30 ] following our previous approach [ 25 , 27 , 79 , 80 ]. Preprocessing for the structural images included (1) image noise reduction, (2) skull stripping using the Brain Extraction Tool (BET), (3) linear and nonlinear registration to the Montreal Neurological Institute (MNI) 152 standard space, and (4) segmentation of the brain into gray matter, white matter, and cerebrospinal fluid (CSF) compartments.…”

Section: Methodsmentioning

confidence: 99%

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

Wang

et al. 2021

Alz Res Therapy

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Wang

et al. 2021

Alz Res Therapy

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“…To investigate the "change-change" brain-cognition association, we The individual rate of change in cognitive performance, defined as the subject-specific slope of the regression line between time and the cognitive scores, was derived from the LME models described in the previous section (Ng et al, 2016(Ng et al, , 2018. The results were visualized using the ggplot (v. 2-3.0.0) package in R.…”

Section: Brain-cognition Associationmentioning

confidence: 99%

Longitudinal functional brain network reconfiguration in healthy aging

Malagurski

Liem

Oschwald

et al. 2020

Human Brain Mapping

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Healthy aging is associated with changes in cognitive performance and functional brain organization. In fact, cross‐sectional studies imply lower modularity and significant heterogeneity in modular architecture across older subjects. Here, we used a longitudinal dataset consisting of four occasions of resting‐state‐fMRI and cognitive testing (spanning 4 years) in 150 healthy older adults. We applied a graph‐theoretic analysis to investigate the time‐evolving modular structure of the whole‐brain network, by maximizing the multilayer modularity across four time points. Global flexibility, which reflects the tendency of brain nodes to switch between modules across time, was significantly higher in healthy elderly than in a temporal null model. Further, global flexibility, as well as network‐specific flexibility of the default mode, frontoparietal control, and somatomotor networks, were significantly associated with age at baseline. These results indicate that older age is related to higher variability in modular organization. The temporal metrics were not associated with simultaneous changes in processing speed or learning performance in the context of memory encoding. Finally, this approach provides global indices for longitudinal change across a given time span and it may contribute to uncovering patterns of modular variability in healthy and clinical aging populations.

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“…The volume change was modeled linearly, as morphological trajectories in studies of gray matter in NPC patients post-RT are linear (11). As described previously (11,31), random intercepts, as well as random slopes for the effect of time (months since RT or baseline), were modeled for each subject to account for inter-individual variability at baseline and differences in the rate of change following RT (32)(33)(34). We constructed two models to elucidate the RT-related brain morphometric changes longitudinally.…”

Section: Longitudinal Brain Morphometric Trajectory In Npc Patients Post-rtmentioning

confidence: 99%

Divergent effects of irradiation on brain cortical morphology in patients with nasopharyngeal carcinoma: one-year follow-up study using structural magnetic resonance imaging

Lv¹,

Guo

Tang³

et al. 2021

Quant Imaging Med Surg

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Background: Increasing evidence indicates that radiotherapy (RT)-induced brain cortical deficits may play a critical role in developing radiation encephalopathy in patients with nasopharyngeal carcinoma (NPC).However, the evolutional processes of RT-induced cortical injury have not been sufficiently investigated.This study investigates RT-induced effects on cortical morphology using longitudinal structural magnetic resonance imaging (MRI) in NPC patients.Methods: Using MRI-based morphometry with surface-based measures, we evaluated the longitudinal alterations of cortical volume (CV), cortical thickness (CT), and cortical surface area (CSA) in 104 NPC patients at pre-RT (n=104), within 3 months post-RT (n=92), 6 months post-RT (n=71), and 9-12 months post-RT (n=52). Twenty healthy controls were also evaluated in parallel. Linear mixed models were used to investigate the trajectories of RT-related changes in cortical brain morphology and its association with irradiation dose, with healthy controls data being used to construct a normal age-related benchmark. The level of statistical significance was set at P<0.05, corrected for multiple comparisons. Results:The results showed that RT-related longitudinal alterations in cortical morphology underwent two diverse patterns during the first year of follow up in NPC patients. The temporal cortices (including the bilateral superior temporal gyrus, middle temporal gyrus, temporal pole, parahippocampal and fusiform gyrus, and the right inferior temporal and right transverse temporal gyrus), the basal occipital cortices (the right lingual gyrus and lateral occipital gyrus), and the basal frontal cortices (the right lateral orbitofrontal gyrus) showed time-dependent attenuation in cortical morphology indices. Furthermore, these effects on multiple cortices were dose-dependent, suggesting they were RT-associated. In contrast, in the left rostral middle frontal gyrus, there was a time-dependent increase in CT.Conclusions: Our preliminary findings revealed divergent effects of irradiation on cortical brain morphology. These results contribute to a more comprehensive understanding of the underlying neural mechanisms of irradiation-related neurotoxic effects on cortical brain morphology and will help guide the investigation of critically neuroprotective strategies. 2308 Lv et al. Divergent effects of irradiation on brain cortical morphology

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Functional segregation loss over time is moderated by APOE genotype in healthy elderly

Cited by 18 publications

References 80 publications

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

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

Longitudinal functional brain network reconfiguration in healthy aging

Divergent effects of irradiation on brain cortical morphology in patients with nasopharyngeal carcinoma: one-year follow-up study using structural magnetic resonance imaging

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