Predicting Progression to Clinical Alzheimer's Disease Dementia Using the Random Survival Forest

J Alzheimers Dis. 2023;95(2):535-548. doi: 10.3233/JAD-230208.

Abstract

Background: Assessing the risk of developing clinical Alzheimer's disease (AD) dementia, by machine learning survival analysis approaches, among participants registered in Alzheimer's Disease Centers is important for AD dementia management.

Objective: To construct a prediction model for the onset time of clinical AD dementia using the National Alzheimer Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) registered cohorts.

Methods: A model was constructed using the Random Survival Forest (RSF) approach and internally and externally validated on the NACC cohort and the ADNI cohort. An R package and a Shiny app were provided for accessing the model.

Results: We built a predictive model having the six predictors: delayed logical memory score (story recall), CDR® Dementia Staging Instrument - Sum of Boxes, general orientation in CDR®, ability to remember dates and ability to pay bills in the Functional Activities Questionnaire, and patient age. The C indices of the model were 90.82% (SE = 0.71%) and 86.51% (SE = 0.75%) in NACC and ADNI respectively. The time-dependent AUC and accuracy at 48 months were 92.48% (SE = 1.12%) and 88.66% (SE = 1.00%) respectively in NACC, and 90.16% (SE = 1.12%) and 85.00% (SE = 1.14%) respectively in ADNI.

Conclusion: The model showed good prediction performance and the six predictors were easy to obtain, cost-effective, and non-invasive. The model could be used to inform clinicians and patients on the probability of developing clinical AD dementia in 4 years with high accuracy.

Keywords: Alzheimer’s disease; dementia; machine learning; survival analysis.

Publication types

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

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Cognitive Dysfunction*
  • Disease Progression
  • Humans
  • Neuroimaging

Grants and funding