title: Predicting progression of Alzheimer's disease using ordinal regression.
abstract: We propose a novel approach to predicting disease progression in Alzheimer's disease (AD)--multivariate ordinal regression--which inherently models the ordered nature of brain atrophy spanning normal aging (CTL) to mild cognitive impairment (MCI) to AD. Ordinal regression provides probabilistic class predictions as well as a continuous index of disease progression--the ORCHID (Ordinal Regression Characteristic Index of Dementia) score. We applied ordinal regression to 1023 baseline structural MRI scans from two studies: the US-based Alzheimer's Disease Neuroimaging Initiative (ADNI) and the European based AddNeuroMed program. Here, the acquired AddNeuroMed dataset was used as a completely independent test set for the ordinal regression model trained on the ADNI cohort providing an optimal assessment of model generalizability. Distinguishing CTL-like (CTL and stable MCI) from AD-like (MCI converters and AD) resulted in balanced accuracies of 82% (cross-validation) for ADNI and 79% (independent test set) for AddNeuroMed. For prediction of conversion from MCI to AD, balanced accuracies of 70% (AUC of 0.75) and 75% (AUC of 0.81) were achieved. The ORCHID score was computed for all subjects. We showed that this measure significantly correlated with MMSE at 12 months (ρ =  -0.64, ADNI and ρ =  -0.59, AddNeuroMed). Additionally, the ORCHID score can help fractionate subjects with unstable diagnoses (e.g. reverters and healthy controls who later progressed to MCI), moderately late converters (12-24 months) and late converters (24-36 months). A comparison with results in the literature and direct comparison with a binary classifier suggests that the performance of this framework is highly competitive.
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Orla M
authors.initials: OM
authors.lastname: Doyle
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom; 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, London, United Kingdom.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Marquand
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: University of Eastern Finland and University Hospital of Kuopio, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: NIHR Biomedical Research Centre for Mental Health at South London, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom; NIHR Biomedical Research Centre for Mental Health at South London, London, United Kingdom; Maudsley NHS Foundation Trust, London, United Kingdom; Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Steve C R
authors.initials: SC
authors.lastname: Williams
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom; NIHR Biomedical Research Centre for Mental Health at South London, London, United Kingdom; NIHR Biomedical Research Unit for Dementia at South London, London, United Kingdom; Maudsley NHS Foundation Trust, London, United Kingdom; Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D012044:Regression Analysis; D012720:Severity of Illness Index