Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts

Alzheimers Dement. 2017 Nov;13(11):1226-1236. doi: 10.1016/j.jalz.2017.03.002. Epub 2017 Apr 17.


Introduction: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach.

Methods: We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters.

Results: In each cohort, a two-clusters solution best fitted the data (cophenetic correlation >0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P < .05).

Conclusions: We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics.

Keywords: Alzheimer's disease; Atypical; Cognition; Heterogeneity; Neuropsychology; Subtypes.

Plain language summary

Alzheimer's disease (AD) is a heterogeneous disorder. We identified two cognitive AD subtypes in four cohorts with a data-driven approach. Nonamnestic AD is associated with distinct neurobiological characteristics.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Cluster Analysis
  • Cognition Disorders / classification*
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Denmark
  • Disease Progression
  • Female
  • Germany
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • United States


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Peptide Fragments
  • amyloid beta-protein (1-42)