A machine learning approach to screen for preclinical Alzheimer's disease.

Journal: Neurobiology of aging
Published Date:

Abstract

Combining multimodal biomarkers could help in the early diagnosis of Alzheimer's disease (AD). We included 304 cognitively normal individuals from the INSIGHT-preAD cohort. Amyloid and neurodegeneration were assessed on F-florbetapir and F-fluorodeoxyglucose PET, respectively. We used a nested cross-validation approach with non-invasive features (electroencephalography [EEG], APOE4 genotype, demographic, neuropsychological and MRI data) to predict: 1/ amyloid status; 2/ neurodegeneration status; 3/ decline to prodromal AD at 5-year follow-up. Importantly, EEG was most strongly predictive of neurodegeneration, even when reducing the number of channels from 224 down to 4, as 4-channel EEG best predicted neurodegeneration (negative predictive value [NPV] = 82%, positive predictive value [PPV] = 38%, 77% specificity, 45% sensitivity). The combination of demographic, neuropsychological data, APOE4 and hippocampal volumetry most strongly predicted amyloid (80% NPV, 41% PPV, 70% specificity, 58% sensitivity) and most strongly predicted decline to prodromal AD at 5 years (97% NPV, 14% PPV, 83% specificity, 50% sensitivity). Thus, machine learning can help to screen patients at high risk of preclinical AD using non-invasive and affordable biomarkers.

Authors

  • Sinead Gaubert
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Institute of Memory and Alzheimer's Disease (IM2A), Centre of excellence of neurodegenerative disease (CoEN) and National Reference Centre for Rare or Early Dementias, Department of Neurology, F75013, Paris, France; Université de Paris, Lariboisière Fernand-Widal Hospital, Cognitive Neurology Center, Paris, France.
  • Marion Houot
    AP-HP, Hôpital Pitié-Salpêtrière, Institute of Memory and Alzheimer's Disease (IM2A), Centre of excellence of neurodegenerative disease (CoEN) and National Reference Centre for Rare or Early Dementias, Department of Neurology, F75013, Paris, France; Center for Clinical Investigation (CIC) Neurosciences, Institut du cerveau et de la Moelle épinière (ICM), F75013, Paris, France; Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Boulevard de l'Hôpital, F-75013, Paris, France.
  • Federico Raimondo
    Department of Computer Science, Faculty of Exact & Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
  • Manon Ansart
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; Inria, Aramis project-team, F-75013, Paris, France.
  • Marie-Constance Corsi
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; Inria, Aramis project-team, F-75013, Paris, France.
  • Lionel Naccache
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; AP-HP, Groupe hospitalier Pitié-Salpêtrière, Department of Neurophysiology, Paris, F-75013, France.
  • Jacobo Diego Sitt
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; Cognitive Neuroimaging Unit, Institut National de la Santé et de la Recherche Médicale, U992, F-91191 Gif/Yvette, France; NeuroSpin Centre, Institute of BioImaging Commissariat à l'Energie Atomique, F-91191 Gif/Yvette, France.
  • Marie-Odile Habert
    Laboratoire d'Imagerie Biomédicale, Inserm, U 1146, CNRS, UMR 7371, Sorbonne Université, F-75013, Paris, France; AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Paris, France.
  • Bruno Dubois
    Institut du Cerveau et de la Moelle épinière, ICM, Paris 75013, France.
  • Fabrizio De Vico Fallani
    Institut du Cerveau, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F75013, Paris, France; Inria, Aramis project-team, F-75013, Paris, France.
  • Stanley Durrleman
    Inria, ARAMIS Project-team, F-75013, Paris, France; Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France; Inserm, U1127, F-75013, Paris, France; CNRS, UMR 7225, F-75013, Paris, France; Sorbonne Université, F-75013, Paris, France.
  • Stéphane Epelbaum
    Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.