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Plasma neurofilament light chain in relation to 10-year change in cognition and neuroimaging markers: a population-based study
van Arendonk J, Wolters FJ, Neitzel J, Vinke EJ, Vernooij MW, Ghanbari M, Ikram MA.. GeroScience, 2023-08-03
Topic: Brain proteins, microglia and lab models
Neurofilament light chain (NfL) is a promising biomarker for risk stratification and disease monitoring of dementia, but its utility in the preclinical disease stage remains uncertain. We determined the association of plasma NfL with (change in) neuroimaging markers and cognition in the population-based Rotterdam Study, using linear and logistic regression and mixed-effects models. Plasma NfL levels were measured using the Simoa NF-light™ assay in 4705 dementia-free participants (mean age 71.9 years, 57% women), who underwent cognitive assessment and brain MRI with repeated assessments over a 10-year follow-up period. Higher plasma NfL was associated with worse cognitive performance at baseline (g-factor: β = - 0.12 (- 0.15; - 0.09), p < 0.001), and accelerated cognitive decline during follow-up on the Stroop color naming task (β = 0.04 (0.02; 0.06), p < 0.001), with a smaller trend for decline in global cognition (g-factor β = - 0.02 (- 0.04; 0.00), p = 0.044). In the subset of 975 participants with brain MRI, higher NfL was associated with poorer baseline white matter integrity (e.g., global mean diffusivity: β = 0.12 (0.06; 0.19), p < 0.001), with similar trends for volume of white matter hyperintensities (β = 0.09 (0.02; 0.16), p = 0.011) and presence of lacunes (OR = 1.55 (1.13; 2.14), p = 0.007). Plasma NfL was not associated with volumes or thickness of the total gray matter, hippocampus, or Alzheimer signature regions. In conclusion, higher plasma NfL levels are associated with cognitive decline and larger burden of primarily white matter pathology in the general population.
Key findings
- Higher plasma NfL was associated with worse cognitive performance at baseline (g-factor: β = - 0.12 (- 0.15; - 0.09), p < 0.001), and accelerated cognitive decline during follow-up on the Stroop color naming task (β = 0.04 (0.02; 0.06), p < 0.001), with a smaller trend for decline in global cognition (g-factor β = - 0.02 (- 0.04; 0.00), p = 0.044).
- In the subset of 975 participants with brain MRI, higher NfL was associated with poorer baseline white matter integrity (e.g., global mean diffusivity: β = 0.12 (0.06; 0.19), p < 0.001), with similar trends for volume of white matter hyperintensities (β = 0.09 (0.02; 0.16), p = 0.011) and presence of lacunes (OR = 1.55 (1.13; 2.14), p = 0.007).
- Plasma NfL was not associated with volumes or thickness of the total gray matter, hippocampus, or Alzheimer signature regions.
- In conclusion, higher plasma NfL levels are associated with cognitive decline and larger burden of primarily white matter pathology in the general population.
Why it matters
In 4,705 dementia-free people, higher plasma neurofilament light was linked to worse baseline cognition, faster decline on one task, and poorer white matter integrity, but not to gray matter volumes or thickness. This concerns a marker of brain injury and risk, not a treatment, cure or prevention.
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Study details
- Participants975
- Effect sizeOR = 1.55
- Evidence strengthLow
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (GeroScience) |
| Journal's citation record | 1 / 4 | GeroScience: journal h-index 83 (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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 975 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 24 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 4.3× 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 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author M. Arfan Ikram: h-index 167 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37535203) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
van Arendonk, J., Wolters, F. J., Neitzel, J., Vinke, E. J., Vernooij, M. W., Ghanbari, M., et al. (2024). Plasma neurofilament light chain in relation to 10-year change in cognition and neuroimaging markers: a population-based study. GeroScience. https://doi.org/10.1007/s11357-023-00876-5
Vancouver
van Arendonk J, Wolters FJ, Neitzel J, Vinke EJ, Vernooij MW, Ghanbari M, et al. Plasma neurofilament light chain in relation to 10-year change in cognition and neuroimaging markers: a population-based study. GeroScience. 2024. doi:10.1007/s11357-023-00876-5. PMID: 37535203.
BibTeX
@article{vanarendonk2024-37535203,
author = {van Arendonk, J. and Wolters, F. J. and Neitzel, J. and Vinke, E. J. and Vernooij, M. W. and Ghanbari, M. and Ikram, M. A.},
title = {{Plasma neurofilament light chain in relation to 10-year change in cognition and neuroimaging markers: a population-based study}},
journal = {GeroScience},
year = {2024},
doi = {10.1007/s11357-023-00876-5},
pmid = {37535203},
url = {https://doi.org/10.1007/s11357-023-00876-5}
}
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