Disrupted Functional Brain Connectome in Individuals at Risk for Alzheimer's Disease
Abstract
Background Alzheimer's disease disrupts the topological architecture of whole-brain connectivity (i.e., the connectome); however, whether this disruption is present in amnestic mild cognitive impairment (aMCI), the prodromal stage of Alzheimer's disease, remains largely unknown. Methods We employed resting-state functional magnetic resonance imaging and graph theory approaches to systematically investigate the topological organization of the functional connectome of 37 patients with aMCI and 47 healthy control subjects. Frequency-dependent brain networks were derived from wavelet-based correlations of both high- and low-resolution parcellation units. Results In the frequency interval .031-.063 Hz, the aMCI patients showed an overall decreased functional connectivity of their brain connectome compared with control subjects. Further graph theory analyses of this frequency band revealed an increased path length of the connectome in the aMCI group. Moreover, the disease targeted several key nodes predominantly in the default-mode regions and key links primarily in the intramodule connections within the default-mode network and the intermodule connections among different functional systems. Intriguingly, the topological aberrations correlated with the patients' memory performance and differentiated individuals with aMCI from healthy elderly individuals with a sensitivity of 86.5% and a specificity of 85.1%. Finally, we demonstrated a high reproducibility of our findings across different large-scale parcellation schemes and validated the test-retest reliability of our network-based approaches. Conclusions This study demonstrates a disruption of whole-brain topological organization of the functional connectome in aMCI. Our finding provides novel insights into the pathophysiological mechanism of aMCI and highlights the potential for using connectome-based metrics as a disease biomarker.
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Clinical studies of patients with AD have demonstrated higher characteristic path lengths of DTI- or fMRI-based connectomes.
“Clinical studies of patients with AD have demonstrated higher characteristic path lengths of DTI- or fMRI-based connectomes (Lo et al., 2010; Wang et al., 2012; Zhao et al., 2012).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Wang et al., 2012
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- Authors
- Wang, J., Zuo, X., Dai, Z., Xia, M., Zhao, Z., Zhao, X., Jia, J., Han, Y., & He, Y.
- Affiliations
- Beijing Normal University (CN)
- Capital Medical University (CN)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 73
- Issue
- 5
- Pages
- 472-481
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2059143861
- Cited by
- 432
- References
- 11
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 18 · 2023: 27 · 2022: 32 · 2021: 31 · 2020: 40 · 2019: 32 · 2018: 33 · 2017: 42 · 2016: 31 · 2015: 39 · 2014: 37 · 2013: 36 · 2012: 1
- FWCI
- 18.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository of Institute of Psychology, Chinese Academy of Sciences (Institute of Psychology, Chinese Academy of Sciences) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- Alzheimer's disease, amnestic mild cognitive impairment, functional connectome, brain network topology, graph theory, resting-state functional connectivity, default mode network, path length, memory performance, disease biomarkers, test-retest reliability
- MeSH terms
- Adult, Aged, Alzheimer Disease, Amnesia, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Risk, Reproducibility of Results, Functional Neuroimaging, Cognitive Dysfunction, Connectome
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