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Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity
Sanz-Arigita EJ, Schoonheim MM, Damoiseaux JS, Rombouts SA, Maris E, Barkhof F, Scheltens P, Stam CJ.. PloS one, 2010-11-01
Topic: Amyloid, tau and blood-test diagnosis
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.
Key findings
- 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.
- 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.
Why it matters
In 18 mild Alzheimer patients compared with 21 healthy controls, the characteristic path length of functional brain networks was closer to random networks, while no significant differences were found in cluster coefficient. This suggests a loss of global information integration in the disease.
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Study details
- Study designpost-hoc analysis
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “post-hoc analysis”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 612 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 34.0 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 19.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 70 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Cornelis J. Stam: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21072180) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Sanz-Arigita, E. J., Schoonheim, M. M., Damoiseaux, J. S., Rombouts, S. A., Maris, E., Barkhof, F., et al. (2010). Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity. PloS one. https://doi.org/10.1371/journal.pone.0013788
Vancouver
Sanz-Arigita EJ, Schoonheim MM, Damoiseaux JS, Rombouts SA, Maris E, Barkhof F, et al. Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity. PloS one. 2010. doi:10.1371/journal.pone.0013788. PMID: 21072180.
BibTeX
@article{sanzarigita2010-21072180,
author = {Sanz-Arigita, E. J. and Schoonheim, M. M. and Damoiseaux, J. S. and Rombouts, S. A. and Maris, E. and Barkhof, F. and Scheltens, P. and Stam, C. J.},
title = {{Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity}},
journal = {PloS one},
year = {2010},
doi = {10.1371/journal.pone.0013788},
pmid = {21072180},
url = {https://doi.org/10.1371/journal.pone.0013788}
}
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