title: Generalizability of the disease state index prediction model for identifying patients progressing from mild cognitive impairment to Alzheimer's disease.
abstract: BACKGROUND
  The Disease State Index (DSI) prediction model measures the similarity of patient data to diagnosed stable and progressive mild cognitive impairment (MCI) cases to identify patients who are progressing to Alzheimer's disease.
  
  
  OBJECTIVE
  We evaluated how well the DSI generalizes across four different cohorts: DESCRIPA, ADNI, AddNeuroMed, and the Kuopio MCI study.
  
  
  METHODS
  The accuracy of the DSI in predicting progression was examined for each cohort separately using 10 × 10-fold cross-validation and for inter-cohort validation using each cohort as a test set for the model built from the other independent cohorts using bootstrapping with 10 repetitions. Altogether 875 subjects were included in the analysis. The analyzed data included a comprehensive set of age and gender corrected magnetic resonance imaging (MRI) features from hippocampal volumetry, multi-template tensor-based morphometry, and voxel-based morphometry as well as Mini-Mental State Examination (MMSE), APOE genotype, and additional cohort specific data from neuropsychological tests and cerebrospinal fluid measurements (CSF).
  
  
  RESULTS
  The DSI model was used to classify the patients into stable and progressive MCI cases. AddNeuroMed had the highest classification results of the cohorts, while ADNI and Kuopio MCI exhibited the lowest values. The MRI features alone achieved a good classification performance for all cohorts. For ADNI and DESCRIPA, adding MMSE, APOE genotype, CSF, and neuropsychological data improved the results.
  
  
  CONCLUSIONS
  The results reveal that the prediction performance of the combined cohort is close to the average of the individual cohorts. It is feasible to use different cohorts as training sets for the DSI, if they are sufficiently similar.
authors.affiliation: Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anette
authors.initials: A
authors.lastname: Hall
authors.affiliation: Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz-Ruiz
authors.affiliation: VTT Technical Research Centre of Finland, Tampere, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Mattila
authors.affiliation: VTT Technical Research Centre of Finland, Tampere, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Koikkalainen
authors.affiliation: Aristotle University of Thessaloniki, Memory and Dementia Centre, "G Papanicolaou" General Hospital, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.affiliation: UMR INSERM, University of Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: National Institute for Health Research (NIHR), London, UK King's College London, Institute of Psychiatry, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands Maastricht University, Maastricht, The Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: VTT Technical Research Centre of Finland, Tampere, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Lötjonen
authors.affiliation: Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics; D019540:Area Under Curve; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000235:genetics / Q000503:physiopathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests
chemical_list: D001057:Apolipoproteins E
keywords: Alzheimer's disease; computer-assisted diagnosis; dementia; magnetic resonance imaging (MRI); mild cognitive impairment