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

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.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.In each cohort, a two-clusters solution best fitted the data (cophenetic correlation0.9): 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).We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics.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.