title: Magnetic resonance imaging improves cerebrospinal fluid biomarkers in the early detection of Alzheimer's disease.
abstract: Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years. CSF measures included total and phosphorylated tau (T-tau, P-tau(231)), amyloid-beta (Abeta(42)/Abeta(40)) and isoprostane. Voxel-based morphometry identified gray matter concentration (GMC) differences best distinguishing study groups and individual GMC values were calculated. Rate of medial temporal lobe (MTL) atrophy was examined using regional boundary shift (rBS) method. At baseline, for MRI, MCI-AD showed reduced GMC-MTL, and for CSF higher CSF T-tau, P-tau(231), IP and lower Abeta(42)/Abeta(40) as compared with MCI-MCI or NL-NL. Longitudinally, rBS-MTL atrophy was higher in MCI-AD than in either MCI-MCI or NL-NL, particularly in the left hemisphere. CSF data showed longitudinally greater increases of isoprostane in MCI-AD as compared with NL-NL. Combining baseline CSF-P-tau(231) and GMC-MTL significantly increased overall prediction of AD from 74% to 84% (p(step)<0.05). These results provide support for including multiple modalities of biomarkers in the identification of memory clinic patients at increased risk for dementia.
authors.affiliation: New York University School of Medicine, Center for Brain Health, NY 10016, USA.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Brys
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Remigiusz
authors.initials: R
authors.lastname: Switalski
authors.forename: Susan
authors.initials: S
authors.lastname: De Santi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rich
authors.forename: Byeong C
authors.initials: BC
authors.lastname: Kim
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mehta
authors.forename: Ray
authors.initials: R
authors.lastname: Zinkowski
authors.forename: Domenico
authors.initials: D
authors.lastname: Pratico
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Wai H
authors.initials: WH
authors.lastname: Tsui
authors.forename: Henry
authors.initials: H
authors.lastname: Rusinek
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D019540:Area Under Curve; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D005260:Female; D007839:Functional Laterality; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D028421:Isoprostanes / Q000134:cerebrospinal fluid; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D028421:Isoprostanes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins