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

Alzheimers Dement. 2021 Nov;17(11):1855-1867. doi: 10.1002/alz.12491. Epub 2021 Nov 10.

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.

Keywords: Alzheimer's disease; amyloid; biomarker profile; machine learning; mild cognitive impairment; neurodegeneration; predictive analytics; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / classification*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers* / cerebrospinal fluid
  • Cognitive Dysfunction / pathology
  • Data Collection
  • Disease Progression*
  • Female
  • Humans
  • Machine Learning / classification*
  • Male
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins

Grants and funding