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Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease
Liu Y, Yu C, Zhang X, Liu J, Duan Y, Alexander-Bloch AF, Liu B, Jiang T et al.. Cerebral cortex (New York, N.Y. : 1991), 2013-01-11
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting-state fMRI measures as biomarkers or predictors of disease progression in AD.
Key findings
- We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex.
- In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology.
- This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18).
- These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency.
Why it matters
In patients with severe Alzheimer's disease, functional connectivity was reduced, particularly between regions separated by greater physical distance, and loss of long-distance connectivity was associated with less efficient network topology. Similar findings were seen in mild Alzheimer's disease and amnestic mild cognitive impairment, but this describes brain changes rather than a treatment.
Study details
- Participants18
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cerebral cortex (New York, N.Y. : 1991)) |
| Journal's citation record | 3 / 4 | Cerebral Cortex: journal h-index 345 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (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 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 18 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 256 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.3 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 11.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 40 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Edward Thomas Bullmore: h-index 183 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23314940) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Liu, Y., Yu, C., Zhang, X., Liu, J., Duan, Y., Alexander-Bloch, A. F., et al. (2014). Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease. Cerebral cortex (New York, N.Y. : 1991). https://doi.org/10.1093/cercor/bhs410
Vancouver
Liu Y, Yu C, Zhang X, Liu J, Duan Y, Alexander-Bloch AF, et al. Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease. Cerebral cortex (New York, N.Y. : 1991). 2014. doi:10.1093/cercor/bhs410. PMID: 23314940.
BibTeX
@article{liu2014-23314940,
author = {Liu, Y. and Yu, C. and Zhang, X. and Liu, J. and Duan, Y. and Alexander-Bloch, A. F. and Liu, B. and Jiang, T. and others},
title = {{Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease}},
journal = {Cerebral cortex (New York, N.Y. : 1991)},
year = {2014},
doi = {10.1093/cercor/bhs410},
pmid = {23314940},
url = {https://doi.org/10.1093/cercor/bhs410}
}
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