title: Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD.
  
  
  OBJECTIVE
  To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD.
  
  
  METHODS
  68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI).
  
  
  RESULTS
  Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%).
  
  
  CONCLUSIONS
  In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.
authors: Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden.
authors: Antoine
authors: A
authors: Leuzy
authors: Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom.
authors: Stephen F
authors: SF
authors: Carter
authors: Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden.
authors: Konstantinos
authors: K
authors: Chiotis
authors: Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Department of Psychology, Stockholm University, Stockholm, Sweden.
authors: Ove
authors: O
authors: Almkvist
authors: Section of Nuclear Medicine and PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors: Anders
authors: A
authors: Wall
authors: Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: Agneta
authors: A
authors: Nordberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000145:classification / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000145:classification / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; [${11}^C$]PIB; amyloid; cerebrospinal fluid; mild cognitive impairment; positron emission tomography; tau