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Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia
Álvarez I, Diez-Fairen M, Aguilar M, González JM, Ysamat M, Tartari JP, Carcel M, Alonso A et al.. European journal of neurology, 2020-12-14
Topic: Risk, prevention and care in population studies
Background and purpose Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia. Methods Amyloid-β (Aβ) 1-42, total tau (t-tau), phosphorylated tau, Aβ 40 , Aβ 38 , beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), neurogranin (ng), phosphorylated neurofilament heavy-chain, and α-synuclein (α-syn) CSF levels were analyzed in 319 subjects, among whom 57 also underwent an amyloid PET scan. We also analyzed longitudinal clinical data from 239 subjects. Results Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels. Conclusions These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.
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APA 7th
Álvarez, I., Diez-Fairen, M., Aguilar, M., González, J. M., Ysamat, M., Tartari, J. P., et al. (2021). Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia. European journal of neurology. https://doi.org/10.1111/ene.14658
Vancouver
Álvarez I, Diez-Fairen M, Aguilar M, González JM, Ysamat M, Tartari JP, et al. Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia. European journal of neurology. 2021. doi:10.1111/ene.14658. PMID: 33236496.
BibTeX
@article{alvarez2021-33236496,
author = {Álvarez, I. and Diez-Fairen, M. and Aguilar, M. and González, J. M. and Ysamat, M. and Tartari, J. P. and Carcel, M. and Alonso, A. and others},
title = {{Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia}},
journal = {European journal of neurology},
year = {2021},
doi = {10.1111/ene.14658},
pmid = {33236496},
url = {https://doi.org/10.1111/ene.14658}
}
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Key findings
- Results Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity.
- In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels.
- Conclusions These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.
Why it matters
Combining newer CSF markers with core Alzheimer's markers improved accuracy in identifying amyloid PET positivity and some ratios predicted faster conversion from mild cognitive impairment to Alzheimer's. These findings are about improving diagnosis and tracking progression, not about treating, curing, or preventing the disease.
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Study details
- Study designlongitudinal study
- Participants319
- Evidence strengthModerate
How this study scored 54/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (European journal of neurology) |
| Journal's citation record | 2 / 4 | European Journal of Neurology: journal h-index 181 (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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 319 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 1.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pau Pástor: h-index 69 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Emory University: institution h-index 1,360 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33236496) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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