Predictive value of ATN biomarker profiles in estimating disease progression in Alzheimer's disease dementia.

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association
Published Date:

Abstract

We aimed to evaluate the value of ATN biomarker classification system (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) for predicting conversion from mild cognitive impairment (MCI) to dementia. In a sample of people with MCI (n = 415) we assessed predictive performance of ATN classification using empirical knowledge-based cut-offs for each component of ATN and compared it to two data-driven approaches, logistic regression and RUSBoost machine learning classifiers, which used continuous clinical or biomarker scores. In data-driven approaches, we identified ATN features that distinguish normals from individuals with dementia and used them to classify persons with MCI into dementia-like and normal groups. Both data-driven classification methods performed better than the empirical cut-offs for ATN biomarkers in predicting conversion to dementia. Classifiers that used clinical features performed as well as classifiers that used ATN biomarkers for prediction of progression to dementia. We discuss that data-driven modeling approaches can improve our ability to predict disease progression and might have implications in future clinical trials.

Authors

  • Ali Ezzati
    Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Ahmed Abdulkadir
    Laboratory for Research in Neuroimaging, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
  • Clifford R Jack
    Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
  • Paul M Thompson
    Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Danielle J Harvey
    Department of Public Health Sciences, University of California-Davis, Davis, CA, USA.
  • Monica Truelove-Hill
    Center for Biomedical Image Computing and Analytics, monica.hill@pennmedicine.upenn.edu christos.davatzikos@uphs.upenn.edu.
  • Lasya P Sreepada
    Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Christos Davatzikos
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Richard B Lipton
    Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.