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Longitudinal Blood-Based Biomarkers and Clinical Progression in Subjective Cognitive Decline
Trieu C, van Harten AC, van Leeuwenstijn MSSA, Schlüter LM, Boonkamp L, Aladdin A, Sikkes SAM, van de Giessen E et al.. JAMA network open, 2025-12-01
Topic: Risk, prevention and care in population studies
Importance Blood-based biomarkers identify Alzheimer disease and hold promise for monitoring disease progression, even in the preclinical disease stages. Objective To investigate longitudinal trajectories of blood-based biomarkers and association with cognitive decline and risk of progression in individuals with subjective cognitive decline (SCD). Design, setting, and participants This prospective cohort study (Subjective Cognitive Impairment Cohort) of individuals with SCD evaluated at a memory clinic underwent biennial biomarker collection and annual cognitive assessment and diagnostic evaluation from January 1, 2005, to December 31, 2023, with follow-up through 2023. Exposure Amyloid status was determined using positron emission tomography or cerebrospinal fluid. Plasma Aβ42/40, phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were measured biennially. Main outcomes and measures Cognitive trajectories in memory, attention, language, executive function, and global cognition and clinical progression to mild cognitive impairment or dementia. Results A total of 298 individuals (mean [SD] age, 61.55 [8.08] years; 174 [58.4%] male) with SCD were included, of whom 80 were amyloid-positive (A+) and 218 were amyloid-negative (A-). Mean (SD) follow-up was 4.8 (2.6) years. Individuals with SCD A+ were older (mean [SD] age, 65.25 [7.14] years; 42 [52.5%] male) than those with SCD A- (mean [SD] age, 60.19 [8.00] years; 132 [60.6%] male). For pTau217, GFAP, and NfL, baseline levels were higher in the A+ group compared with A- group (estimates [SE] amyloid β, 1.11 [0.11], 0.69 [0.13], and 0.36 [0.10], respectively; P Conclusions and relevance This cohort study of individuals with SCD suggests that longitudinal plasma pTau217 and GFAP are suitable biomarkers for monitoring AD pathology. Their changes were associated with cognitive decline and clinical progression, supporting their potential utility for early intervention and disease monitoring.
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APA 7th
Trieu, C., van Harten, A. C., van Leeuwenstijn, M. S. S. A., Schlüter, L. M., Boonkamp, L., Aladdin, A., et al. (2025). Longitudinal Blood-Based Biomarkers and Clinical Progression in Subjective Cognitive Decline. JAMA network open. https://doi.org/10.1001/jamanetworkopen.2025.45862
Vancouver
Trieu C, van Harten AC, van Leeuwenstijn MSSA, Schlüter LM, Boonkamp L, Aladdin A, et al. Longitudinal Blood-Based Biomarkers and Clinical Progression in Subjective Cognitive Decline. JAMA network open. 2025. doi:10.1001/jamanetworkopen.2025.45862. PMID: 41335440.
BibTeX
@article{trieu2025-41335440,
author = {Trieu, C. and van Harten, A. C. and van Leeuwenstijn, M. S. S. A. and Schlüter, L. M. and Boonkamp, L. and Aladdin, A. and Sikkes, S. A. M. and van de Giessen, E. and others},
title = {{Longitudinal Blood-Based Biomarkers and Clinical Progression in Subjective Cognitive Decline}},
journal = {JAMA network open},
year = {2025},
doi = {10.1001/jamanetworkopen.2025.45862},
pmid = {41335440},
url = {https://doi.org/10.1001/jamanetworkopen.2025.45862}
}
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Key findings
- Results A total of 298 individuals (mean [SD] age, 61.55 [8.08] years; 174 [58.4%] male) with SCD were included, of whom 80 were amyloid-positive (A+) and 218 were amyloid-negative (A-).
- For pTau217, GFAP, and NfL, baseline levels were higher in the A+ group compared with A- group (estimates [SE] amyloid β, 1.11 [0.11], 0.69 [0.13], and 0.36 [0.10], respectively; P < .001 for all).
- Their changes were associated with cognitive decline and clinical progression, supporting their potential utility for early intervention and disease monitoring.
Why it matters
In 298 people with subjective cognitive decline, blood levels of pTau217 and GFAP were higher in those who were amyloid-positive, and the study suggests these markers track with progression. This is an observational cohort study, so it does not show that measuring these blood markers prevents or treats Alzheimer's disease.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcohort study
- Participants298
- Effect size58.4%; 52.5%; 60.6%
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA network open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 298 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Wiesje M. van der Flier: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Vrije Universiteit Amsterdam: institution h-index 1,014 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41335440) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2025.45862
- PubMed: 41335440
- Original source →
- Free full text: JAMA Network Open →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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