title: Detection of Alzheimer's disease signature in MR images seven years before conversion to dementia: Toward an early individual prognosis.
abstract: Finding very early biomarkers of Alzheimer's Disease (AD) to aid in individual prognosis is of major interest to accelerate the development of new therapies. Among the potential biomarkers, neurodegeneration measurements from MRI are considered as good candidates but have so far not been effective at the early stages of the pathology. Our objective is to investigate the efficiency of a new MR-based hippocampal grading score to detect incident dementia in cognitively intact patients. This new score is based on a pattern recognition strategy, providing a grading measure that reflects the similarity of the anatomical patterns of the subject under study with dataset composed of healthy subjects and patients with AD. Hippocampal grading was evaluated on subjects from the Three-City cohort, with a followup period of 12 years. Experiments demonstrate that hippocampal grading yields prediction accuracy up to 72.5% (P < 0.0001) 7 years before conversion to AD, better than both hippocampal volume (58.1%, P = 0.04) and MMSE score (56.9%, P = 0.08). The area under the ROC curve (AUC) supports the efficiency of imaging biomarkers with a gain of 8.4 percentage points for hippocampal grade (73.0%) over hippocampal volume (64.6%). Adaptation of the proposed framework to clinical score estimation is also presented. Compared with previous studies investigating new biomarkers for AD prediction over much shorter periods, the very long followup of the Three-City cohort demonstrates the important clinical potential of the proposed imaging biomarker. The high accuracy obtained with this new imaging biomarker paves the way for computer-based prognostic aides to help the clinician identify cognitively intact subjects that are at high risk to develop AD.
authors.affiliation: Laboratoire Bordelais De Recherche En Informatique, Unité Mixte De Recherche CNRS (UMR 5800), PICTURA Research Group, Bordeaux, France.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Coupé
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Fonov
authors.affiliation: University of Bordeaux, INCIA, UMR 5287, Talence, France.|CNRS, INCIA, UMR 5287, Talence, France.|École Pratique des Hautes Études, Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bernard
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Azar
authors.initials: A
authors.lastname: Zandifar
authors.affiliation: Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Eskildsen
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Département de Pharmacologie CHU de Bordeaux, University of Bordeaux, Bordeaux, France.|INSERM, CIC 14.01, Module EC, Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Helmer
authors.affiliation: Instituto De Aplicaciones De Las Tecnologías De La Información Y De Las Comunicaciones Avanzadas (ITACA), Universitat Politècnica De València, Camino De Vera S/N, Valencia, 46022, Spain.
authors.forename: José V
authors.initials: JV
authors.lastname: Manjón
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Département de Pharmacologie CHU de Bordeaux, University of Bordeaux, Bordeaux, France.|INSERM, CIC 14.01, Module EC, Bordeaux, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Amieva
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Département de Pharmacologie CHU de Bordeaux, University of Bordeaux, Bordeaux, France.|University Hospital, Memory Consultation, CMRR, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.affiliation: University of Bordeaux, INCIA, UMR 5287, Talence, France.|CNRS, INCIA, UMR 5287, Talence, France.|École Pratique des Hautes Études, Bordeaux, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Allard
authors.affiliation: University of Bordeaux, INCIA, UMR 5287, Talence, France.|CNRS, INCIA, UMR 5287, Talence, France.|École Pratique des Hautes Études, Bordeaux, France.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Catheline
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: D Louis
authors.initials: DL
authors.lastname: Collins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D019540:Area Under Curve; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D003704:Dementia / Q000473:pathology*; D018450:Disease Progression; D001330:Electronic Data Processing; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D015203:Reproducibility of Results
keywords: Alzheimer; MRI biomarker; hippocampus