Examining heterogeneity in dementia using data-driven unsupervised clustering of cognitive profiles

PLoS One. 2024 Nov 14;19(11):e0313425. doi: 10.1371/journal.pone.0313425. eCollection 2024.

Abstract

Dementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia's underlying heterogeneity, rather than assuming that the cohort is homogenous. However, current studies on dementia subtyping have the following limitations: (i) focusing on AD-related dementia only and not examining heterogeneity within dementia as a whole, (ii) using only cross-sectional baseline visit information for clustering and (iii) predominantly relying on expensive imaging biomarkers as features for clustering. In this study, we seek to overcome such limitations, using a data-driven unsupervised clustering algorithm named SillyPutty, in combination with hierarchical clustering on cognitive assessment scores to estimate subtypes within a real-world clinical dementia cohort. We use a longitudinal patient data set for our clustering analysis, instead of relying only on baseline visits, allowing us to explore the ongoing temporal relationship between subtypes and disease progression over time. Results showed that subtypes with very mild or mild dementia were more heterogenous in their cognitive profiles and risk of disease progression.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Algorithms
  • Cluster Analysis
  • Cognition*
  • Cognitive Dysfunction / diagnosis
  • Cross-Sectional Studies
  • Dementia* / diagnosis
  • Dementia* / epidemiology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Neuropsychological Tests

Grants and funding

The preparation of this manuscript was supported by the Centene Corporation contract (P19-00559) for the Washington University-Centene ARCH Personalized Medicine Initiative. There was no additional external funding received for this study.