title: Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls.
abstract: We used a new method we developed for automated hippocampal segmentation, called the auto context model, to analyze brain MRI scans of 400 subjects from the Alzheimer's disease neuroimaging initiative. After training the classifier on 21 hand-labeled expert segmentations, we created binary maps of the hippocampus for three age- and sex-matched groups: 100 subjects with Alzheimer's disease (AD), 200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age: 75.84; SD: 6.64). Hippocampal traces were converted to parametric surface meshes and a radial atrophy mapping technique was used to compute average surface models and local statistics of atrophy. Surface-based statistical maps visualized links between regional atrophy and diagnosis (MCI versus controls: P = 0.008; MCI versus AD: P = 0.001), mini-mental state exam (MMSE) scores, and global and sum-of-boxes clinical dementia rating scores (CDR; all P < 0.0001, corrected). Right but not left hippocampal atrophy was associated with geriatric depression scores (P = 0.004, corrected); hippocampal atrophy was not associated with subsequent decline in MMSE and CDR scores, educational level, ApoE genotype, systolic or diastolic blood pressure measures, or homocysteine. We gradually reduced sample sizes and used false discovery rate curves to examine the method's power to detect associations with diagnosis and cognition in smaller samples. Forty subjects were sufficient to discriminate AD from normal and correlate atrophy with CDR scores; 104, 200, and 304 subjects, respectively, were required to correlate MMSE with atrophy, to distinguish MCI from normal, and MCI from AD.
authors.affiliation: Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Morra
authors.forename: Zhuowen
authors.initials: Z
authors.lastname: Tu
authors.forename: Liana G
authors.initials: LG
authors.lastname: Apostolova
authors.forename: Amity E
authors.initials: AE
authors.lastname: Green
authors.forename: Christina
authors.initials: C
authors.lastname: Avedissian
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Madsen
authors.forename: Neelroop
authors.initials: N
authors.lastname: Parikshak
authors.forename: Xue
authors.initials: X
authors.lastname: Hua
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuff
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods*; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D012016:Reference Values; D012680:Sensitivity and Specificity