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© 2009 American Academy of Neurology CSF biomarkers in relationship to cognitive profiles in Alzheimer diseaseFrom the Departments of Neurology and Alzheimer Center (A.E.v.d.V., N.A.V., F.H.B., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., M.A.B.), and Medical Psychology (M.K.), VU University Medical Center, Amsterdam, the Netherlands. Address correspondence and reprint requests to Dr van der Vlies, Department of Neurology and Alzheimer Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands, ae.vdvlies{at}vumc.nl 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 (Aβ1-42), 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 Aβ1-42 and low levels of tau and p-tau. Cluster 2 contained 72 patients (41%) with relatively low levels of Aβ1-42 and high levels of tau and p-tau. Cluster 3 was made up of 17 patients (10%) with low levels of Aβ1-42 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.
Abbreviations: Aβ1-42 = amyloid-beta 1-42; AD = Alzheimer disease; CDR = Clinical Dementia Rating; CJD = Creutzfeldt-Jacob disease; DS = Digit Span; FTD = frontotemporal dementia; LP = lumbar puncture; MANOVA = multivariate analysis of variance; MMSE = Mini-Mental State Examination; p-tau = tau phosphorylated at threonine 181; TMT = Trail Making Test; VAT = Visual Association Test.
The Alzheimer Centre VUMC is supported by Alzheimer Nederland and Stichting VUMC fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Disclosure: The authors report no disclosures. Received September 9, 2008. Accepted in final form December 5, 2008. This article has been cited by other articles:
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