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Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study
Cronjé HT, Liu X, Odden MC, Moseholm KF, Seshadri S, Satizabal CL, Lopez OL, Bis JC, Djoussé L, Fohner AE, Psaty BM, Tracy RP, et al.. Alzheimer's & Dementia, 2023-07-01
Topic: Brain proteins, microglia and lab models
Introduction Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. Methods We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. Results In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline. Discussion Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.
Key findings
- Introduction Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk.
- Results In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality.
- Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9).
- NfL was independently associated with accelerated cognitive decline.
Why it matters
In 1712 dementia-free older adults followed for 19 years, being in the highest versus lowest tertile of serum NfL or GFAP was associated with higher risk of incident dementia and dementia-specific mortality, and the joint highest tertile was associated with even higher risk. This suggests these blood markers may provide clinical insight into dementia risk and prognosis, but it does not show that lowering them prevents or treats dementia.
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Study details
- Study designcohort
- Participants1,712
- Effect sizeHR 2.06 for incident dementia and 9.22 for dementia mortality with both NfL and GFAP in the top tertile
- Evidence strengthModerate
Limitations
Biomarker trajectories over time could not be assessed; few dementia-specific deaths produced wide confidence intervals in stratified analyses; observational design with possible measurement error and residual confounding; dementia outcomes were indirectly determined for many participants; serum rather than plasma may have reduced sensitivity, particularly for total tau.
How this study scored 72/100
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. We have no data on free to read, so that was left out: it earned 71 of the 98 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,712 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 | 4 / 7 | Cited 53 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.6 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 9.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kenneth Jay Mukamal: h-index 97 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37392405) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 71 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 71 of the 98 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Cronjé, H. T., Liu, X., Odden, M. C., Moseholm, K. F., Seshadri, S., Satizabal, C. L., et al. (2023). Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimer's & Dementia. https://doi.org/10.1002/alz.13367
Vancouver
Cronjé HT, Liu X, Odden MC, Moseholm KF, Seshadri S, Satizabal CL, et al. Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimer's & Dementia. 2023. doi:10.1002/alz.13367. PMID: 37392405.
BibTeX
@article{cronje2023-37392405,
author = {Cronjé, H. T. and Liu, X. and Odden, M. C. and Moseholm, K. F. and Seshadri, S. and Satizabal, C. L. and Lopez, O. L. and Bis, J. C. and Djoussé, L. and Fohner, A. E. and Psaty, B. M. and Tracy, R. P. and others},
title = {{Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study}},
journal = {Alzheimer's \& Dementia},
year = {2023},
doi = {10.1002/alz.13367},
pmid = {37392405},
url = {https://doi.org/10.1002/alz.13367}
}
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