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Comparative Prognostic Performance of Hippocampal Volume and Plasma Biomarkers in Amyloid-Negative Subjective Cognitive Decline: A Four-Year Follow-up
Bora Yoon, Hyuk-je Lee, Yun Jeong Hong, Kee Hyung Park, SangYun Kim, Min Jeong Wang, Seong Hye Choi, Sungmin Kang et al.. Journal of Clinical Neurology, 2026-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background and Purpose Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia.However, the prognosis of patients with amyloid-negative (A-) SCD remains unclear.We investigated whether baseline plasma and imaging biomarkers predict four-year clinical progression in A-SCD.Methods Sixty-five individuals with A-SCD were followed for four years.Baseline plasma biomarkers-phosphorylated tau 181 (pTau181), glial fibrillary acidic protein, neurofilament light chain (NfL), and pTau181/Aβ42 ratio-and MRI markers (hippocampal volume and white matter hyperintensity [WMH] grade) were assessed.Outcomes included MCI conversion and cognitive progression defined as ≥1-point (Prog-1) or ≥2-point (Prog-2) decline in Korean Mini-Mental State Examination.Predictive performance was evaluated using multivariable logistic regression and bootstrap-validated receiver operating characteristic analyses.Results Fourteen participants (21.5%) converted to MCI, and 24 (36.9%) were classified as Prog-1.Plasma biomarkers did not show consistent predictive performance across predefined endpoints (all p>0.05), although NfL demonstrated modest discrimination for MCI conversion (area under the curve [AUC] 0.686, p=0.008).Hippocampal volume demonstrated significant discriminative performance for MCI conversion (AUC 0.765, p=0.016) and Prog-1 (AUC 0.933, p<0.001).For Prog-2, hippocampal volume showed high discrimination (AUC 0.952, p<0.001).WMH grade also demonstrated significant discrimination for MCI conversion (AUC 0.835, p<0.001) and Prog-1 (AUC 0.857, p<0.001).Bootstrap analyses (1,000 iterations) tended to show higher AUC estimates for imaging markers compared with plasma biomarkers. ConclusionsIn this A-SCD cohort, hippocampal atrophy demonstrated more consistent prognostic performance than Alzheimer' s dis ease-focused plasma biomarkers for predicting four-year conversion to MCI and cognitive decline, suggesting a potential role for MRI-based neurodegeneration markers in clinical risk stratification.
Key findings
- Background and Purpose Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia.However, the prognosis of patients with amyloid-negative (A-) SCD remains unclear.We investigated whether baseline plasma and imaging biomarkers predict four-year clinical progression i
- ConclusionsIn this A-SCD cohort, hippocampal atrophy demonstrated more consistent prognostic performance than Alzheimer' s dis ease-focused plasma biomarkers for predicting four-year conversion to MCI and cognitive decline, suggesting a potential role for MRI-based neurodegeneration markers in clinical risk stratification.
Why it matters
In 65 people with amyloid-negative subjective cognitive decline followed for four years, plasma biomarkers did not show consistent predictive performance, while hippocampal volume predicted conversion to mild cognitive impairment and cognitive progression. This indicates that imaging may outperform Alzheimer's-focused plasma markers in this group, but it is a small cohort and offers no treatment or cure.
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Study details
- Effect size21.5%; 36.9%; AUC 0.765
- Evidence strengthModerate
How this study scored 43/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Clinical Neurology) |
| Journal's citation record | 1 / 4 | Journal of Clinical Neurology: journal h-index 75 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Dong Won Yang: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Seoul National University: institution h-index 1,053 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42683796) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
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Read the original
- DOI: 10.3988/jcn.2025.0659
- PubMed: 42683796
- Original source →
- Free full text: Journal of Clinical Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Yoon, B., Lee, H.-j., Hong, Y. J., Park, K. H., Kim, S., Wang, M. J., et al. (2026). Comparative Prognostic Performance of Hippocampal Volume and Plasma Biomarkers in Amyloid-Negative Subjective Cognitive Decline: A Four-Year Follow-up. Journal of Clinical Neurology. https://doi.org/10.3988/jcn.2025.0659
Vancouver
Yoon B, Lee H.-j, Hong YJ, Park KH, Kim S, Wang MJ, et al. Comparative Prognostic Performance of Hippocampal Volume and Plasma Biomarkers in Amyloid-Negative Subjective Cognitive Decline: A Four-Year Follow-up. Journal of Clinical Neurology. 2026. doi:10.3988/jcn.2025.0659. PMID: 42683796.
BibTeX
@article{yoon2026-42683796,
author = {Yoon, Bora and Lee, Hyuk-je and Hong, Yun Jeong and Park, Kee Hyung and Kim, SangYun and Wang, Min Jeong and Choi, Seong Hye and Kang, Sungmin and others},
title = {{Comparative Prognostic Performance of Hippocampal Volume and Plasma Biomarkers in Amyloid-Negative Subjective Cognitive Decline: A Four-Year Follow-up}},
journal = {Journal of Clinical Neurology},
year = {2026},
doi = {10.3988/jcn.2025.0659},
pmid = {42683796},
url = {https://doi.org/10.3988/jcn.2025.0659}
}
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