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Cited by 608Functional Brain Connectivity StudiesDementia and Cognitive Impairment ResearchComplex Network Analysis Techniques

Loss of ‘Small-World’ Networks in Alzheimer's Disease: Graph Analysis of fMRI Resting-State Functional Connectivity

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Sanz-Arigita, Ernesto J., Schoonheim, Menno M., Damoiseaux, Jessica S., Rombouts, Serge A. R. B., Maris, Erik, Barkhof, Frederik, Scheltens, Philip, Stam, Cornelis J.·2010·PLoS ONE
DOI 10.1371/journal.pone.0013788PMC PMC2967467
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Abstract

BACKGROUND: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data. METHODOLOGY/PRINCIPAL FINDINGS: 18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions. CONCLUSIONS/SIGNIFICANCE: We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease.

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  • Some studies have observed conflicting results, including lower characteristic path length in DTI, gray matter, fMRI, EEG, and MEG connectomes in patients with AD.

    “However, some studies have observed conflicting results, including lower characteristic path length in DTI (Daianu et al., 2013), gray matter (Tijms, Moller et al., 2013), fMRI (Sanz-Arigita et al., 2010), EEG (de Haan et al., 2009), and magneto-encephalogram (MEG; Stam et al., 2009) connectomes in patients with AD.”

    From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Sanz-Arigita et al., 2010

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Authors
Sanz-Arigita, E. J., Schoonheim, M. M., Damoiseaux, J. S., Rombouts, S. A. R. B., Maris, E., Barkhof, F., Scheltens, P., & Stam, C. J.
Affiliations
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Stanford University (US)
  • Leiden University (NL)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-11-01
Volume
5
Issue
11
Pages
e13788
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0013788
PMC
PMC2967467
OpenAlex
W2011541551
Cited by
608
References
11
Citations by year
2026: 20 · 2025: 26 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 34 · 2020: 34 · 2019: 50 · 2018: 67 · 2017: 39 · 2016: 47 · 2015: 47 · 2014: 50 · 2013: 62 · 2012: 33
FWCI
21.34
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (acceptedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
Keywords
Alzheimer's disease, resting-state functional connectivity, small-world networks, average path length, clustering coefficient, early Alzheimer's disease
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Neurological, Nerve Net, Rest, Young Adult

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