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CSF biomarkers in relationship to cognitive profiles in Alzheimer disease.
Neurology. 2009 Mar 24; 72(12):1056-61.Neur

Abstract

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.

Authors+Show Affiliations

Department of Neurology and Alzheimer Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. ae.vdvlies@vumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19307538

Citation

van der Vlies, A E., et al. "CSF Biomarkers in Relationship to Cognitive Profiles in Alzheimer Disease." Neurology, vol. 72, no. 12, 2009, pp. 1056-61.
van der Vlies AE, Verwey NA, Bouwman FH, et al. CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. Neurology. 2009;72(12):1056-61.
van der Vlies, A. E., Verwey, N. A., Bouwman, F. H., Blankenstein, M. A., Klein, M., Scheltens, P., & van der Flier, W. M. (2009). CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. Neurology, 72(12), 1056-61. https://doi.org/10.1212/01.wnl.0000345014.48839.71
van der Vlies AE, et al. CSF Biomarkers in Relationship to Cognitive Profiles in Alzheimer Disease. Neurology. 2009 Mar 24;72(12):1056-61. PubMed PMID: 19307538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. AU - van der Vlies,A E, AU - Verwey,N A, AU - Bouwman,F H, AU - Blankenstein,M A, AU - Klein,M, AU - Scheltens,P, AU - van der Flier,W M, PY - 2009/3/25/entrez PY - 2009/3/25/pubmed PY - 2009/9/10/medline SP - 1056 EP - 61 JF - Neurology JO - Neurology VL - 72 IS - 12 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19307538/CSF_biomarkers_in_relationship_to_cognitive_profiles_in_Alzheimer_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=19307538 DB - PRIME DP - Unbound Medicine ER -