title: Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease.
abstract: We assessed the diagnostic utility of 3 CSF biomarkers-14-3-3 protein, total tau (T-tau), and neuron-specific enolase (NSE)-from the same lumbar puncture to distinguish between participants with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease (sCJD, n = 57) and controls with nonprion rapidly progressive dementia (npRPD, n = 41). Measures of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, as well as logistic regression and area under the receiver operator curve (AUC), were used to assess the ability of these CSF biomarkers, alone or concomitantly, to predict diagnosis. In a subcohort with available MRI (sCJD n = 57, npRPD = 32), we compared visual assessment of diffusion-weighted imaging MRI sequences to these CSF biomarkers. MRI was the best predictor, with an AUC of 0.97 (confidence interval [CI] 0.92-1.00) and a diagnostic accuracy of 97% (CI 90%-100%). Of the CSF biomarkers, T-tau had a higher diagnostic accuracy (79.6%) than 14-3-3 (70.4%, CI for difference 8.7%, 9.7%;p= 0.048) or NSE (71.4%, CI for difference 7.6%, 8.7%;p= 0.03).
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Sven A
authors.initials: SA
authors.lastname: Forner
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Leonel T
authors.initials: LT
authors.lastname: Takada
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Brianne M
authors.initials: BM
authors.lastname: Bettcher
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Tartaglia
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Charles
authors.initials: C
authors.lastname: Torres-Chae
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Aissatou
authors.initials: A
authors.lastname: Haman
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Julie
authors.initials: J
authors.lastname: Thai
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitali
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Alan
authors.initials: A
authors.lastname: Bostrom
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: Memory and Aging Center (SAF, BMB, IVL, CT-C, AH, JN, AB, BLM, HLR, MDG), Department of Neurology, University of California San Francisco; Department of Neurology (LTT), Hospital das Clinicas, University of Sao Paulo Medical School, Brazil; Tanz Centre for Research in Neurodegenerative Disease (MCT), University of Toronto, Canada; Division of Geriatrics (JT), San Francisco Veterans Affairs Medical Center and University of California at San Francisco; and the Brain MRI 3T Mondino Research Center (PV), C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind