Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials.

Autor:	Rosenberg GA; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico, USA Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA., Prestopnik J; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA., Adair JC; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA., Huisa BN; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA., Knoefel J; Department of Geriatrics, University of New Mexico, Albuquerque, New Mexico, USA., Caprihan A; The MIND Research Network, Albuquerque, New Mexico, USA., Gasparovic C; The MIND Research Network, Albuquerque, New Mexico, USA., Thompson J; Department of Neurology, University of New Mexico, Albuquerque, New Mexico, USA., Erhardt EB; Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico, USA., Schrader R; Clinical and Translational Science Center, Albuquerque, New Mexico, USA.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2015 Dec; Vol. 86 (12), pp. 1324-30. Date of Electronic Publication: 2015 Jan 24.
DOI:	10.1136/jnnp-2014-309421
Abstrakt:	Objectives: Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. Methods: We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-β1-42 and phosphorylated-τ181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses. Results: An initial BDS of 6 or greater was significantly correlated with a final diagnosis of BD (p<0.05; area under the curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The most predictive of BD was the factor containing the inflammatory biomarkers of increased BBB permeability, elevated albumin index and reduced MMP-2 index (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD, and combining them improved the diagnostic accuracy. Conclusions: Biomarkers predicted the diagnosis of the BD type of subcortical ischaemic vascular disease. Using pathophysiological biomarkers to select homogeneous groups of patients needs to be tested in targeted treatment trials. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
Databáze:	MEDLINE
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