title: Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis.
abstract: Purpose To investigate the diagnostic accuracy of an image-based classifier to distinguish between Alzheimer disease (AD) and behavioral variant frontotemporal dementia (bvFTD) in individual patients by using gray matter (GM) density maps computed from standard T1-weighted structural images obtained with multiple imagers and with independent training and prediction data. Materials and Methods The local institutional review board approved the study. Eighty-four patients with AD, 51 patients with bvFTD, and 94 control subjects were divided into independent training (n = 115) and prediction (n = 114) sets with identical diagnosis and imager type distributions. Training of a support vector machine (SVM) classifier used diagnostic status and GM density maps and produced voxelwise discrimination maps. Discriminant function analysis was used to estimate suitability of the extracted weights for single-subject classification in the prediction set. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for image-based classifiers and neuropsychological z scores. Results Training accuracy of the SVM was 85% for patients with AD versus control subjects, 72% for patients with bvFTD versus control subjects, and 79% for patients with AD versus patients with bvFTD (P ≤ .029). Single-subject diagnosis in the prediction set when using the discrimination maps yielded accuracies of 88% for patients with AD versus control subjects, 85% for patients with bvFTD versus control subjects, and 82% for patients with AD versus patients with bvFTD, with a good to excellent AUC (range, 0.81-0.95; P ≤ .001). Machine learning-based categorization of AD versus bvFTD based on GM density maps outperforms classification based on neuropsychological test results. Conclusion The SVM can be used in single-subject discrimination and can help the clinician arrive at a diagnosis. The SVM can be used to distinguish disease-specific GM patterns in patients with AD and those with bvFTD as compared with normal aging by using common T1-weighted structural MR imaging. (©) RSNA, 2015.
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Christiane
authors.initials: C
authors.lastname: Möller
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Adriaan
authors.initials: A
authors.lastname: Versteeg
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Betty
authors.initials: B
authors.lastname: Tijms
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Jan C
authors.initials: JC
authors.lastname: de Munck
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Anne
authors.initials: A
authors.lastname: Hafkemeijer
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: John
authors.initials: J
authors.lastname: van Swieten
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Elise
authors.initials: E
authors.lastname: Dopper
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: From the Alzheimer Center and Department of Neurology (C.M., Y.A.L.P., W.M.v.d.F., B.T., E.D., P.S.), Department of Epidemiology and Biostatistics (W.M.v.d.F.), Department of Radiology and Nuclear Medicine (A.V., F.B., H.V., A.M.W.), Department of Physics and Medical Technology (J.C.d.M., H.V.), and Department of Clinical Genetics (J.v.S.), Neuroscience Campus Amsterdam, VU University Medical Center, APO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Psychology (A.H., S.A.R.B.R., E.D.) and Leiden Institute for Brain and Cognition (A.H., S.A.R.B.R.), Leiden University, Leiden, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (A.H., S.A.R.B.R., J.v.d.G.); and Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands (J.v.S., E.D.).
authors.forename: Alle Meije
authors.initials: AM
authors.lastname: Wink
mesh_terms: D000544:Alzheimer Disease / Q000145:classification* / Q000473:pathology*; D001284:Atrophy; D003937:Diagnosis, Differential; D005260:Female; D057180:Frontotemporal Dementia / Q000145:classification* / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012372:ROC Curve; D060388:Support Vector Machine