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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 ageand 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 5 0.008; MCI versus AD: P 5 0.001), mini-mental state exam (MMSE) scores, and global and sum-ofboxes clinical dementia rating scores (CDR; all P < 0.0001, corrected). Right but not left hippocampal atrophy was associated with geriatric depression scores (P 5 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 J_ID: HBM Wiley Ed. Ref. No.: 08-0177.R1 Customer A_ID: HBM20708 Date: 1-DECEMBER-08 Stage: I Page: 1 ID: vasanss Date: 1/12/08 Time: 19:21 Path: J:/Production/HBM#/Vol00000/080197/3B2/C2HBM#080197 Contract grant sponsor: NIH; Contract grant number: U01 AG024904; Contract grant sponsor: The National Center for Research Resources; Contract grant numbers: AG016570, EB01651, LM05639, RR019771; Contract grant sponsors: The National Institute of Aging, The National Institute of Biomedical Imaging and Bioengineering (NIBIB), The Foundation for the National Institutes of Health, Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, the Alzheimer’s Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, The Institute for the Study of Aging (ISOA), The U.S. Food and Drug Administration, The Northern California Institute for Research and Education, The NIA, NIBIB, The National Library of Medicine AQ11 . *Correspondence to: Paul Thompson, Professor of Neurology, Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Neuroscience Research Building 225E, 635 Charles Young Drive, Los Angeles, CA 90095-1769, USA. E-mail: [email protected] Received for publication 15 May 2008; Revised 3 September 2008; Accepted 2 November 2008 DOI: 10.1002/hbm.20708 Published online in Wiley InterScience (www.interscience.wiley.