Defining multivariate normative rules for healthy aging using neuroimaging and machine learning: an application to Alzheimer's disease

J Alzheimers Dis. 2015;43(1):201-12. doi: 10.3233/JAD-140189.

Abstract

Background: Neuroimaging techniques combined with computational neuroanatomy have been playing a role in the investigation of healthy aging and Alzheimer's disease (AD). The definition of normative rules for brain features is a crucial step to establish typical and atypical aging trajectories.

Objective: To introduce an unsupervised pattern recognition method; to define multivariate normative rules of neuroanatomical measures; and to propose a brain abnormality index.

Methods: This study was based on a machine learning approach (one class classification or novelty detection) to neuroanatomical measures (brain regions, volume, and cortical thickness) extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s database. We applied a ν-One-Class Support Vector Machine (ν-OC-SVM) trained with data from healthy subjects to build an abnormality index, which was compared with subjects diagnosed with mild cognitive impairment and AD.

Results: The method was able to classify AD subjects as outliers with an accuracy of 84.3% at a false alarm rate of 32.5%. The proposed brain abnormality index was found to be significantly associated with group diagnosis, clinical data, biomarkers, and future conversion to AD.

Conclusion: These results suggest that one-class classification may be a promising approach to help in the detection of disease conditions. Our findings support a framework considering the continuum of brain abnormalities from healthy aging to AD, which is correlated with cognitive impairment and biomarkers measurements.

Keywords: Dementia; neurodegeneration; neuroimaging; normative; outliers; pattern recognition; support vector machines.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Alzheimer Disease / classification
  • Alzheimer Disease / pathology
  • Brain / pathology*
  • Cognitive Dysfunction / classification
  • Cognitive Dysfunction / pathology
  • Databases, Factual
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted / methods*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organ Size
  • Pattern Recognition, Automated / methods
  • Sensitivity and Specificity
  • Support Vector Machine*
  • Unsupervised Machine Learning