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Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease
Gao Y, Sengupta A, Li M, Zu Z, Rogers BP, Anderson AW, Ding Z, Gore JC et al.. PloS one, 2020-10-16
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Objective In vivo functional changes in white matter during the progression of Alzheimer's disease (AD) have not been previously reported. Our objectives are to measure changes in white matter functional connectivity (FC) in an elderly population undergoing cognitive decline as AD develops, to establish their relationship to neuropsychological scores of cognitive abilities, and to assess the performance in prediction of AD using white matter FC measures as features. Methods Analyses were conducted using resting state functional MRI and neuropsychological data from 383 ADNI participants, including 136 cognitive normal (CN) controls, 46 with significant memory concern, 83 with early mild cognitive impairment (MCI), 37 with MCI, 46 with late MCI, and 35 with AD dementia. FC metrics between segregated white matter tracts and discrete gray matter volumes or between white matter tracts were quantitatively analyzed and characterized, along with their relationships to 6 cognitive measures. Finally, supervised machine learning was implemented on white matter FCs to classify the participants and performance of the classification was evaluated. Results Significant decreases in FC measures were found in white matter with prominent, specific, regional deficits appearing in late MCI and AD dementia patients from CN. These changes significantly correlated with neuropsychological measurements of impairments in cognition and memory. The sensitivity and specificity of distinguishing AD dementia and CN using white matter FCs were 0.83 and 0.81 respectively. Conclusions and relevance The white matter FC decreased in late MCI and AD dementia patients compared to CN participants, and this decrease was correlated with cognitive measures. White matter FC is valuable in the prediction of AD. All these findings suggest that white matter FC may be a promising avenue for understanding functional impairments in white matter tracts during AD progression.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gao, Y., Sengupta, A., Li, M., Zu, Z., Rogers, B. P., Anderson, A. W., et al. (2020). Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease. PloS one. https://doi.org/10.1371/journal.pone.0240513
Vancouver
Gao Y, Sengupta A, Li M, Zu Z, Rogers BP, Anderson AW, et al. Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease. PloS one. 2020. doi:10.1371/journal.pone.0240513. PMID: 33064765.
BibTeX
@article{gao2020-33064765,
author = {Gao, Y. and Sengupta, A. and Li, M. and Zu, Z. and Rogers, B. P. and Anderson, A. W. and Ding, Z. and Gore, J. C. and others},
title = {{Functional connectivity of white matter as a biomarker of cognitive decline in Alzheimer's disease}},
journal = {PloS one},
year = {2020},
doi = {10.1371/journal.pone.0240513},
pmid = {33064765},
url = {https://doi.org/10.1371/journal.pone.0240513}
}
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Key findings
- Methods Analyses were conducted using resting state functional MRI and neuropsychological data from 383 ADNI participants, including 136 cognitive normal (CN) controls, 46 with significant memory concern, 83 with early mild cognitive impairment (MCI), 37 with MCI, 46 with late MCI, and 35 with AD dementia.
- Results Significant decreases in FC measures were found in white matter with prominent, specific, regional deficits appearing in late MCI and AD dementia patients from CN.
- These changes significantly correlated with neuropsychological measurements of impairments in cognition and memory.
- Conclusions and relevance The white matter FC decreased in late MCI and AD dementia patients compared to CN participants, and this decrease was correlated with cognitive measures.
- All these findings suggest that white matter FC may be a promising avenue for understanding functional impairments in white matter tracts during AD progression.
Why it matters
This study of 383 people found that functional connectivity in white matter decreased with cognitive decline in Alzheimer's disease, with specific regional deficits appearing in late mild cognitive impairment and Alzheimer's dementia, and these changes correlated with thinking test scores. It is about using brain imaging as a marker of decline, not about treating, curing or preventing the disease.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 41 of the 96 points we could judge it on, which is 43 out of 100.
| 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 | 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 | 2 / 5 | 2020 — within 10 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 59 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Vanderbilt University: institution h-index 1,199 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33064765) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 41 of the 96 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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