Abnormal Functional Brain Networks in Mild Cognitive Impairment and Alzheimer’s Disease: A Minimum Spanning Tree Analysis

Wang, Bin; Miao, Liwen; Niu, Yan; Cao, Rui; Li, Dandan; Yan, Pengfei; Guo, Hao; Yan, Tianyi; Wu, Jinglong; Xiang, Jie; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.3233/jad-180603

Cited by 18 publications

(12 citation statements)

References 56 publications

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“…had lower values, indicating that these subjects have weaker local information processing capacity. The above results show attenuated long-distance functional connections and decreased local functional connections in the brain network of subjects with the PDE4D variants, and these network properties were very similar to those found in previous studies examining brain networks in subjects showing cognitive impairment (Bassett and Sporns, 2017;Murphy and Fox, 2017;Rathore et al, 2017;Wang et al, 2018;Yan et al, 2018). This supports our hypothesis that PDE4D variants can be neurotoxic and even lead to cognitive impairment.…”

Section: Abnormal Network Topologies Associated With Pde4d Variantssupporting

confidence: 90%

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2020

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is affected by several genetic variants. It has been demonstrated that genetic variants affect brain organization and function. In this study, using whole genome-wide association studies (GWAS), we analyzed the functional magnetic resonance imaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative dataset (ADNI) dataset and identified genetic variants associated with the topology of the functional brain network http://www. adni-info.org. We found three novel loci (rs2409627, rs9647533, and rs11955845) in an intron of the phosphodiesterase 4D (PDE4D) gene that contribute to abnormalities in the topological organization of the functional network. In particular, compared to the wildtype genotype, the subjects carrying the PDE4D variants had altered network properties, including a significantly reduced clustering coefficient, small-worldness, global and local efficiency, a significantly enhanced path length and a normalized path length. In addition, we found that all global brain network attributes were affected by PDE4D variants to different extents as the disease progressed. Additionally, brain regions with alterations in nodal efficiency due to the variations in PDE4D were predominant in the limbic lobe, temporal lobe and frontal lobes. PDE4D has a great effect on memory consolidation and cognition through long-term potentiation (LTP) effects and/or the promotion of inflammatory effects. PDE4D variants might be a main reasons underlyling for the abnormal topological properties and cognitive impairment. Furthermore, we speculated that PDE4D is a risk factor for neural degenerative diseases and provided important clues for the earlier detection and therapeutic intervention for AD.

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Section: Abnormal Network Topologies Associated With Pde4d Variantssupporting

confidence: 90%

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2020

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“…Generally, the brain connectome has been directly probed by structural connectivity (SC) derived from diffusion-tensor imaging (DTI), which represents anatomical wiring diagrams, and functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (fMRI), which reflects the synchronization of neuronal activities in different brain regions (5,6). Recently, researchers have argued that the functional network connections of the human brain are limited by the potential anatomical white matter pathway (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The association between SC and FC, called structuralfunctional (SC-FC) coupling, and the joint study of SC and FC can describe the functional dynamics of the brain from a structural topological perspective and may detect subtle brain changes more sensitively than any single imaging modality (7,18,19).…”

Section: Introductionmentioning

confidence: 99%

Abnormal Anatomical Rich-Club Organization and Structural–Functional Coupling in Mild Cognitive Impairment and Alzheimer's Disease

et al. 2020

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Emerging research indicates interruptions in the wiring organization of the brain network in Mild cognitive impairment (MCI) and Alzheimer's disease (AD). Due to the important role of rich-club organization in distinguishing abnormalities of AD patients and the close relationship between structural connectivity (SC) and functional connectivity (FC), our study examined whether changes in SC-FC coupling and the relationship with abnormal rich-club organizations during the development of diseases may contribute to the pathophysiology of AD. Structural diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) were performed in 38 normal controls (NCs), 40 MCI patients and 19 AD patients. Measures of the rich-club structure and its role in global structural-functional coupling were administered. Our study found decreased levels of feeder and local connectivity in MCI and AD patients, which were the main contributing factors to the lower efficiency of the brain structural network. Another important finding was that we have more accurately characterized the changing pattern of functional brain dynamics. The enhanced coupling between SC and FC in MCI and AD patients might be due to disruptions in optimal structural organization. More interestingly, we also found increases in the SC-FC coupling for feeder and local connections in MCI and AD patients. SC-FC coupling also showed significant differences between MCI and AD patients, mainly between the abnormal feeder connections. The connection density and coupling strength were significantly correlated with clinical metrics in patients. The present findings enhanced our understanding of the neurophysiologic mechanisms associated with MCI and AD.

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“…Resting-state functional magnetic resonance imaging (rfMRI) has been increasingly used as a reliable method (Zuo and Xing, 2014) to detect brain network abnormalities in aMCI (Agosta et al, 2012; Bharath et al, 2017; Wang et al, 2018b) or AD (Binnewijzend et al, 2014; Wang et al, 2018b). The rfMRI findings in AD and MCI are rather consistent across different studies in different networks, such as default mode network (Agosta et al, 2012), somatomotor network (Albers et al, 2015), dorsal attention network (Qian et al, 2015), limbic network (Nestor et al, 2003), and frontoparietal control network (Agosta et al, 2012; Brier et al, 2012; Munro et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Functional Connectivity Changes Across the Spectrum of Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

Wang

Qiao

Chen

et al. 2019

Front. Neuroinform.

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The abnormality occurs at molecular, cellular as well as network levels in patients with Alzheimer’s disease (AD) prior to diagnosis. Most previous connectivity studies were conducted at 1 out of 3 (local, meso and global) scales in subjects covering only part of the entire AD spectrum (subjective cognitive decline, SCD; amnestic mild cognitive impairment, aMCI; and then fully manifest AD). Data interpretation within the framework of disease progression is therefore difficult. The current study included 3 age- and sex-matched cohorts: SCD ( n = 32), aMCI ( n = 37) and fully-established AD ( n = 30). A group of healthy elderly subjects ( n = 40) were included as a normal control (NC). Network connectivity was examined at the local (degree centrality), meso [subgraph centrality (SC)], and global (eigenvector and page-rank centralities) levels. As compared to NC, SCD subjects had isolated decrease of SC in primary (somatomotor and visual) networks. aMCI subjects had decreased centralities at all three scales in associative (frontoparietal control, dorsal attention, limbic and default) networks. AD subjects had increased centrality at the global scale in all seven networks. There was a positive association between Montreal Cognitive Assessment (MoCA) scores and DC in the frontoparietal control network in SCD, a negative relationship between Mini-Mental State Examination (MMSE) scores and EC in the somatomotor network in AD. These findings suggest that the primary network is impaired as early as in SCD. Impairment in the associative network also starts at the local level at this stage and may contribute to the cognitive decline. As associative network impairment extends from local to meso and global scales in aMCI, compensatory mechanisms in the primary network are activated.

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Abnormal Functional Brain Networks in Mild Cognitive Impairment and Alzheimer’s Disease: A Minimum Spanning Tree Analysis

Cited by 18 publications

References 56 publications

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer’s Disease

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer’s Disease

Abnormal Anatomical Rich-Club Organization and Structural–Functional Coupling in Mild Cognitive Impairment and Alzheimer's Disease

Functional Connectivity Changes Across the Spectrum of Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

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