Neuropsychological phenotypic characteristics in a cohort of community-based older adults: Data from the Framingham Heart Study

Background: Neuropsychological (NP) assessment is crucial for diagnosing prodromal and Alzheimer's disease and related dementia (ADRD) syndromes. Yet, traditional NP scores often overlook errors and the process by which summary scores are obtained; information that can provide deeper insights into cognitive impairments and clinical heterogeneity. Objective: To classify community-dwelling adults into neurocognitive phenotypes, identify NP test errors and processes that differentiate between groups, and explore their association with brain imaging measures. Methods: Framingham Heart Study (FHS) data were analyzed, focusing on NP summary scores and errors derived from the Boston Process Approach. Latent class analysis identified distinct neurocognitive phenotypes. Regression analyses assessed the relationships with NP errors and brain MRI measures. Results: A total of 1195 participants (mean age 69.6 and 56.3% women) were included. Cognitively normal (CN), moderate-mixed, and dysexecutive impairment groups were identified. The number of Trail Making Test – Part B (TMT-B) pen lifts and TMT-B examiner-corrected errors were associated with the dysexecutive phenotype and differentiated it from the CN group (OR = 1.39, 95% CI = 1.28–1.52, p < 0.001, AUC = 0.85 and OR = 3.40, 95% CI = 2.65–4.38, p < 0.001, AUC = 0.92; respectively). Similarly, Boston Naming Test (BNT) circumlocution errors were associated with the moderate-mixed phenotype and differentiated it from the CN group (OR = 1.87, 95% CI = 1.49–2.35, p < 0.001, AUC = 0.81). These scores were significantly associated with reduced hippocampal volumes. Conclusions: Detailed NP error and process analysis enhances traditional methods, offering a comprehensive approach to identifying and understanding cognitive impairments.