Data-driven versus consensus diagnosis of MCI: enhanced sensitivity for detection of dementia progression, biomarker status, and neuropathological outcomes

Objective: Given prior work demonstrating that mild cognitive impairment (MCI) can be empirically differentiated into meaningful cognitive subtypes, we applied actuarial methods to comprehensive neuropsychological data from the University of California San Diego (UCSD) Alzheimer’s Disease Research Center (ADRC) in order to identify cognitive subgroups within nondemented ADRC participants, and to examine cognitive, biomarker, and neuropathological trajectories.

Methods: Cluster analysis was performed on baseline neuropsychological data (n=738; mean age=71.8). Survival analysis examined progression to dementia (mean follow-up=5.9 years). CSF AD biomarker status and neuropathological findings at follow-up were examined in a subset with available data.

Results: Five clusters were identified: \"optimal\" cognitively normal (CN; n=130) with above-average cognition, \"typical\" CN (n=204) with average cognition, non-amnestic MCI (naMCI; n=104), amnestic MCI (aMCI; n=216), and mixed MCI (mMCI...