Measurement Error and Methodologic Issues in Analyses of the Proportion of Variance Explained in Cognition.

Existing studies examining the predictive ability of biomarkers for cognitive outcomes do not account for variance due to measurement error, which could lead to under-estimates of the proportion of variance explained. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1084) to estimate the proportion of variance explained by Alzheimer's disease (AD) imaging biomarkers in four cognitive outcomes: memory, executive functioning, language, and visuospatial functioning. We compared estimates from standard models that do not account for measurement error, and multilevel models that do account for measurement error. We also examined estimates across diagnostic subgroups (normal, MCI, AD). Estimates of the proportion of variance explained from multilevel models accounting for measurement error were larger (e.g., for language, 9-47% vs. 7-34% under standard modeling), with relatively greater differences between standard and multilevel measurement models for cognitive outcomes that have larger measurement error variance. Heterogeneity across subgroups also emphasized the importance of sample composition. Future studies should evaluate measurement error adjustments when considerable measurement error in cognitive outcomes is suspected.