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Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study
Martino-Adami PV, Chatterjee M, Kleineidam L, Weyerer S, Bickel H, Wiese B, Riedel-Heller SG, Scherer M et al.. The Lancet regional health. Europe, 2024-08-16
Topic: Amyloid, tau and blood-test diagnosis
Background Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care. Methods We measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79-94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later). Findings Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17-1.51]), NfL (HR = 1.19 [95% CI: 1.03-1.36]), and GFAP (HR = 1.36 [95% CI: 1.22-1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68-0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = -0.49 [95% CI: -0.71 to 0.26]), NfL (β = -0.29 [95% CI: -0.52 to 0.06]), and GFAP (β = -0.60 [95% CI: -0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14-0.25]), NfL (β = 2.88 [95% CI: 2.18-3.59]), and GFAP (β = 8.23 [95% CI: 6.71-9.75]). NfL (β = 2.47 [95% CI: 1.04-3.89]) and GFAP (β = 4.45 [95% CI: 1.38-7.51]) exhibited a faster increase in individuals progressing to DAT. Interpretation Evaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care. Funding Alzheimer Forschung Initiative, Bundesministerium für Bildung und Forschung.
Key findings
- Background Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers.
- Findings Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17-1.51]), NfL (HR = 1.19 [95% CI: 1.03-1.36]), and GFAP (HR = 1.36 [95% CI: 1.22-1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68-0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT.
Why it matters
In 1,007 people aged 79-94 without dementia from primary care, higher P-tau181, NfL, and GFAP and a lower Aβ42/Aβ40 ratio were linked to greater risk of later Alzheimer's dementia and faster cognitive decline. Combining a brief cognitive test with these blood markers improved identification of who would develop dementia.
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Study details
- Study designlongitudinal study
- Participants1,007
- Effect sizeHR = 1.32; HR = 1.19; HR = 1.36
- Evidence strengthModerate
How this study scored 64/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Lancet regional health. Europe) |
| Journal's citation record | 1 / 4 | The Lancet Regional Health - Europe: journal h-index 88 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,007 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 4.1× 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 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alfredo Ramı́rez: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 24 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39253733) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1016/j.lanepe.2024.101030
- PubMed: 39253733
- Original source →
- Free full text: The Lancet Regional Health - Europe →
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
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APA 7th
Martino-Adami, P. V., Chatterjee, M., Kleineidam, L., Weyerer, S., Bickel, H., Wiese, B., et al. (2024). Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study. The Lancet regional health. Europe. https://doi.org/10.1016/j.lanepe.2024.101030
Vancouver
Martino-Adami PV, Chatterjee M, Kleineidam L, Weyerer S, Bickel H, Wiese B, et al. Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study. The Lancet regional health. Europe. 2024. doi:10.1016/j.lanepe.2024.101030. PMID: 39253733.
BibTeX
@article{martinoadami2024-39253733,
author = {Martino-Adami, P. V. and Chatterjee, M. and Kleineidam, L. and Weyerer, S. and Bickel, H. and Wiese, B. and Riedel-Heller, S. G. and Scherer, M. and others},
title = {{Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study}},
journal = {The Lancet regional health. Europe},
year = {2024},
doi = {10.1016/j.lanepe.2024.101030},
pmid = {39253733},
url = {https://doi.org/10.1016/j.lanepe.2024.101030}
}
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