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Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression
Diniz BS, Sibille E, Ding Y, Tseng G, Aizenstein HJ, Lotrich F, Becker JT, Lopez OL et al.. Molecular psychiatry, 2014-08-05
Topic: Brain proteins, microglia and lab models
Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment. The biological mechanisms underlying cognitive impairment in LLD are complex and likely involve abnormalities in multiple pathways, or 'cascades,' reflected in specific biomarkers. Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD. To this end, we used a data-driven comprehensive proteomic analysis (multiplex immunoassay including 242 proteins), along with measures of structural brain abnormalities (gray matter atrophy and white matter hyperintensity volume via magnetic resonance imaging), and brain amyloid-β (Aβ) deposition (PiB-positron emission tomography). We analyzed data from 80 older adults with remitted major depression (36 with mild cognitive impairment (LLD+MCI) and 44 with normal cognitive (LLD+NC)) function. LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis. Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015). We observed no differences in gray matter volume or brain Aβ deposition between groups. Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias). Cognitive impairment in LLD seems to be related to greater cerebrovascular disease along with abnormalities in immune-inflammatory control, cell survival, intracellular signaling, protein and lipid homeostasis, and clotting processes. These results suggest that individuals with LLD and cognitive impairment may be more vulnerable to accelerated brain aging and shed light on possible mediators of their elevated risk for progression to dementia.
Key findings
- Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD.
- LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis.
- Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015).
- We observed no differences in gray matter volume or brain Aβ deposition between groups.
- Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias).
Why it matters
In 80 older adults with remitted depression, those with mild cognitive impairment had different levels of 24 blood proteins and more white matter hyperintensities, but no difference in brain amyloid. It is about biological markers in late-life depression and does not test any treatment, cure or prevention.
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Study details
- Effect size81.3%; 86.4%; 76.3%
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (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 | 2015 — 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 5 / 7 | Cited 115 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.8 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 8.3× 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 | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Meryl A. Butters: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25092249) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 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'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
Diniz, B. S., Sibille, E., Ding, Y., Tseng, G., Aizenstein, H. J., Lotrich, F., et al. (2015). Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression. Molecular psychiatry. https://doi.org/10.1038/mp.2014.76
Vancouver
Diniz BS, Sibille E, Ding Y, Tseng G, Aizenstein HJ, Lotrich F, et al. Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression. Molecular psychiatry. 2015. doi:10.1038/mp.2014.76. PMID: 25092249.
BibTeX
@article{diniz2015-25092249,
author = {Diniz, B. S. and Sibille, E. and Ding, Y. and Tseng, G. and Aizenstein, H. J. and Lotrich, F. and Becker, J. T. and Lopez, O. L. and others},
title = {{Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression}},
journal = {Molecular psychiatry},
year = {2015},
doi = {10.1038/mp.2014.76},
pmid = {25092249},
url = {https://doi.org/10.1038/mp.2014.76}
}
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