Quantification of cognitive impairment to characterize heterogeneity of patients at risk of developing Alzheimer's disease dementia.

Introduction: Neuropsychological test scores are limited and standard outcomes may mask the heterogeneity of cognitive impairment. This article presents the calculation and evaluation of six composite scores that quantify domain-specific impairment.

Methods: Parameters for composite scores calculation were learned by performing confirmatory factor analysis in a sample of participants from the Alzheimer's Disease Neuroimaging Initiative database. The obtained scores were evaluated with a separate sample of mild cognitive impairment (MCI) in two automated tasks: unsupervised partition in different subgroups and prediction of progression to dementia for different time windows.

Results: MCI subgroups with distinctive cognitive profiles and risk of progression emerged from cluster analysis. Composite scores outperform standard neuropsychological tests when automatically predicting progression within time windows up to 5 years.

Conclusions: Domain-specific composite scores are useful to delineate profiles of impairment, stratify the MCI risk, and predict progression to dementia.