title: A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity.
abstract: Alzheimer's disease (AD) researchers commonly use MRI as a quantitative measure of disease severity. Historically, hippocampal volume has been favored. Recently, "AD signature" measurements of gray matter (GM) volumes or cortical thicknesses have gained attention. Here, we systematically evaluate multiple thickness- and volume-based candidate-methods side-by-side, built using the popular FreeSurfer, SPM, and ANTs packages, according to the following criteria: (a) ability to separate clinically normal individuals from those with AD; (b) (extent of) correlation with head size, a nuisance covariatel (c) reliability on repeated scans; and (d) correlation with Braak neurofibrillary tangle stage in a group with autopsy. We show that volume- and thickness-based measures generally perform similarly for separating clinically normal from AD populations, and in correlation with Braak neurofibrillary tangle stage at autopsy. Volume-based measures are generally more reliable than thickness measures. As expected, volume measures are highly correlated with head size, while thickness measures are generally not. Because approaches to statistically correcting volumes for head size vary and may be inadequate to deal with this underlying confound, and because our goal is to determine a measure which can be used to examine age and sex effects in a cohort across a large age range, we thus recommend thickness-based measures. Ultimately, based on these criteria and additional practical considerations of run-time and failure rates, we recommend an AD signature measure formed from a composite of thickness measurements in the entorhinal, fusiform, parahippocampal, mid-temporal, inferior-temporal, and angular gyrus ROIs using ANTs with input segmentations from SPM12.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA. Electronic address: schwarz.christopher@mayo.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Schwarz
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.affiliation: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.affiliation: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Chadwick P
authors.initials: CP
authors.lastname: Ward
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: Department of Neuroscience (Neuropathology), Mayo Clinic and Foundation, Jacksonville, FL, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.affiliation: Department of Neuroscience (Neuropathology), Mayo Clinic and Foundation, Jacksonville, FL, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Veterans Affairs, University of California, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology; D015331:Cohort Studies; D066264:Datasets as Topic; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales