Abstract
BACKGROUND: Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify etiology and even facilitate the identification of patient subtypes with common neuropathology and clinical course. METHODS: We compared trajectories (mean duration of 3.5years) of cognitive impairments in a sample of 201 community-dwelling schizophrenia (SCZ) patients (aged 40-100years) with 67 healthy comparison (HC) subjects. We employed growth mixture models to discover subclasses with more homogenous between-subject variation in cognitive trajectories. Post hoc analyses determined factors associated with class membership and class-specific correlates of cognitive trajectories. RESULTS: Three latent classes were indicated: Class 1 (85% HC and 50% SCZ) exhibited relatively high and stable trajectories of cognition, Class 2 (15% HC and 40% SCZ) exhibited lower, modestly declining trajectories, and Class 3 (10% SCZ) exhibited lower, more rapidly declining trajectories. Within the patient group, membership in Classes 2-3 was associated with worse negative symptoms and living in a board and care facility. DISCUSSION: These results bridge the gap between schizophrenia studies demonstrating cognitive decline and those demonstrating stability. Moreover, a finer-grained characterization of heterogeneity in cognitive trajectories has practical implications for interventions and for case management of patients who show accelerated cognitive decline. Such a characterization requires study designs and analyses sensitive to between- and within-patient heterogeneity in outcomes.