title: Automated Hippocampal Subfield Measures as Predictors of Conversion from Mild Cognitive Impairment to Alzheimer's Disease in Two Independent Cohorts.
abstract: Previous studies have shown that hippocampal subfields may be differentially affected by Alzheimer's disease (AD). This study used an automated analysis technique and two large cohorts to (1) investigate patterns of subfield volume loss in mild cognitive impairment (MCI) and AD, (2) determine the pattern of subfield volume loss due to age, gender, education, APOE ε4 genotype, and neuropsychological test scores, (3) compare combined subfield volumes to hippocampal volume alone at discriminating between AD and healthy controls (HC), and predicting future MCI conversion to AD at 12 months. 1,069 subjects were selected from the AddNeuroMed and Alzheimer's disease neuroimaging initiative (ADNI) cohorts. Freesurfer was used for automated segmentation of the hippocampus and hippocampal subfields. Orthogonal partial least squares to latent structures (OPLS) was used to train models on AD and HC subjects using one cohort for training and the other for testing and the combined cohort was used to predict MCI conversion. MANCOVA and linear regression analyses showed multiple subfield volumes including Cornu Ammonis 1 (CA1), subiculum and presubiculum were atrophied in AD and MCI and were related to age, gender, education, APOE ε4 genotype, and neuropsychological test scores. For classifying AD from HC, combined subfield volumes achieved comparable classification accuracy (81.7%) to total hippocampal (80.7%), subiculum (81.2%) and presubiculum (80.6%) volume. For predicting MCI conversion to AD combined subfield volumes and presubiculum volume were more accurate (81.1%) than total hippocampal volume. (76.7%).
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.
authors.forename: Wasim
authors.initials: W
authors.lastname: Khan
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.|Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.|NIHR Biomedical Research Centre for Mental Health, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Jones
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: INSERM U 558, University of Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.affiliation: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK.|NIHR Biomedical Research Centre for Mental Health, London, UK.
authors.forename: J-Sebastian
authors.initials: JS
authors.lastname: Muehlboeck
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK. andy.simmons@kcl.ac.uk.|NIHR Biomedical Research Centre for Mental Health, London, UK. andy.simmons@kcl.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000473:pathology*; D005260:Female; D005544:Forecasting; D006624:Hippocampus / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests