Abstract
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-β (Aβ)1 - 42, in patients with MCI, as compared to neuroimaging
biomarkers.
Methods: We identified 408 MCI subjects with CSF Aβ 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 Aβ status.
Results: The 30-min delayed recall score of the Rey Auditory Verbal Learning
Test was the best predictor of Aβ 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.
