Utility of Combinations of Biomarkers, Cognitive Markers, and Risk Factors to Predict Conversion From Mild Cognitive Impairment to Alzheimer Disease in Patients in the Alzheimer's Disease Neuroimaging Initiative

Context: Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological A beta 1-42 and total tau, cognitive measures, and individual risk factors. Objective: To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Design: Longitudinal study. Participants: We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n=116) and those who did not convert (n=204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. Setting: The Alzheimer's Disease Neuroimaging Initiative public database. Outcome Measures: Primary outcome measures were odds ratios, pseudo-R2s, and effect sizes. Results: In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Conclusions: Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.