Neuropsychological Testing Predicts Cerebrospinal Fluid Amyloid-β in Mild Cognitive Impairment

Background: Psychometric tests predict conversion of mild cognitive impairment (MCI) to probable Alzheimer's disease (AD). Because the definition of clinical AD relies on those same psychometric tests, the ability of these tests to identify underlying AD pathology remains unclear. Objective: To determine the degree to which psychometric testing predicts molecular evidence of AD amyloid pathology, as indicated by cerebrospinal fluid (CSF) amyloid-beta (A beta)(1-42), in patients with MCI, as compared to neuroimaging biomarkers. Methods: We identified 408 MCI subjects with CSF A beta levels, psychometric test data, FDG-PET scans, and acceptable volumetric MR scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used psychometric tests and imaging biomarkers in univariate and multivariate models to predict A beta status. Results: The 30-min delayed recall score of the Rey Auditory Verbal Learning Test was the best predictor of A beta status among the psychometric tests, achieving an AUC of 0.67 +/- 0.02 and odds ratio of 2.5 +/- 0.4. FDG-PET was the best imaging-based biomarker (AUC 0.67 +/- 0.03, OR 3.2 +/- 1.2), followed by hippocampal volume (AUC 0.64 +/- 0.02, OR 2.4 +/- 0.3). A multivariate analysis based on the psychometric tests improved on the univariate predictors, achieving an AUC of 0.68 +/- 0.03 (OR 3.38 +/- 1.2). Adding imaging biomarkers to the multivariate analysis did not improve the AUC. Conclusion: Psychometric tests perform as well as imaging biomarkers to predict presence of molecular markers of AD pathology in MCI patients and should be considered in the determination of the likelihood that MCI is due to AD.