CSF biomarkers in relationship to cognitive profiles in Alzheimer disease
van der Vlies AE, Verwey NA, Bouwman FH, Blankenstein MA, Klein M, Scheltens P, van der Flier WM.. Neurology, 2009-03-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To investigate the relationship between CSF biomarkers and cognitive profiles in Alzheimer disease (AD). Methods We included 177 patients with AD. Digit Span, Visual Association Test (VAT), VAT object naming, Trail Making Test (TMT), and category fluency were used to assess cognitive functions. Disease severity was assessed using Mini-Mental State Examination; functional impairment was rated by Clinical Dementia Rating. In CSF, levels of amyloid-beta 1-42 (Abeta(1-42)), tau, and tau phosphorylated at threonine 181 (p-tau) were measured. K-means cluster analysis was performed with the three biomarkers to obtain three clusters. Multivariate analysis of variance for repeated measures was performed with CSF cluster as between-subjects factor, neuropsychological z scores as within-subjects variable, and age, sex, and education as covariates. Results Cluster 1 consisted of 88 patients (49%) with relatively high levels of Abeta(1-42) and low levels of tau and p-tau. Cluster 2 contained 72 patients (41%) with relatively low levels of Abeta(1-42) and high levels of tau and p-tau. Cluster 3 was made up of 17 patients (10%) with low levels of Abeta(1-42) and very high levels of tau and p-tau. No differences between clusters on age, sex, education, APOE genotype, disease duration, functional impairment, or disease severity were found. Patients in cluster 3 performed worse on VAT, TMT-A and -B, and fluency. Conclusions Clusters of CSF biomarker levels are related to cognitive profiles in Alzheimer disease. A subgroup of patients with extremely high CSF levels of tau and tau phosphorylated at threonine 181 shows a distinct cognitive profile with more severe impairment of memory, mental speed, and executive functions, which cannot be explained by disease severity.
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APA 7th
van der Vlies, A. E., Verwey, N. A., Bouwman, F. H., Blankenstein, M. A., Klein, M., Scheltens, P., et al. (2009). CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. Neurology. https://doi.org/10.1212/01.wnl.0000345014.48839.71
Vancouver
van der Vlies AE, Verwey NA, Bouwman FH, Blankenstein MA, Klein M, Scheltens P, et al. CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. Neurology. 2009. doi:10.1212/01.wnl.0000345014.48839.71. PMID: 19307538.
BibTeX
@article{vandervlies2009-19307538,
author = {van der Vlies, A. E. and Verwey, N. A. and Bouwman, F. H. and Blankenstein, M. A. and Klein, M. and Scheltens, P. and van der Flier, W. M.},
title = {{CSF biomarkers in relationship to cognitive profiles in Alzheimer disease}},
journal = {Neurology},
year = {2009},
doi = {10.1212/01.wnl.0000345014.48839.71},
pmid = {19307538},
url = {https://doi.org/10.1212/01.wnl.0000345014.48839.71}
}
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Key findings
- Results Cluster 1 consisted of 88 patients (49%) with relatively high levels of Abeta(1-42) and low levels of tau and p-tau.
Why it matters
In 177 people who already had Alzheimer's, a spinal-fluid test split them into three groups. The smallest group, 17 people (10%), had very high tau and p-tau, and it did worse on tests of memory, mental speed and executive function. That group did not differ from the others in age, education, APOE genotype, disease duration or overall severity, which suggests that Alzheimer's can look different in different people. This is a one-time snapshot, not a treatment study, and it does not show that tau causes the difference.
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Study details
- Participants177
- Evidence strengthLow
How this study scored 51/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 1 / 5 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 177 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 106 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.6 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 6.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 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 | Amsterdam UMC Location Vrije Universiteit Amsterdam: institution h-index 938 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19307538) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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