Subjective vs. Objective Memory Predictors of AD Biomarkers and Future Cognitive, Clinical, and Functional Decline

Abstract

AbstractBackgroundSubjective and objective memory have been previously linked to Alzheimer’s disease (AD) biomarkers and future clinical and cognitive decline. We the ability of two subjective memory assessments and two objective memory assessments to predict cross‐sectional amyloid, tau, and neurodegenerative (A/T/N) biomarkers, as well as future cognitive, clinical, and functional decline.Methods298 participants from ADNI were included, specifically 128 with normal cognition without memory concerns (CN), 123 with significant memory concerns (SMC; defined as a score of ≥20 on the first 12 items of the Cognitive Change Index (CCI)), and 47 with early mild cognitive impairment (EMCI). Objective memory was defined as immediate and delayed scores of Logical Memory and the Rey AVLT (RAVLT). Subjective memory measures included the memory sub‐scores of the ECog and CCI. Baseline Aβ and tau positivity were defined as positive on either neuroimaging and/or CSF biomarkers using standard cut‐offs. Neurodegeneration positive was defined as a hippocampal volume w‐score of 1.5 standard deviations below all CNs with 3T MRI in ADNI (adjusted for age, sex, and total intracranial volume). Cognitive decline was defined as a negative slope on the MMSE, while functional decline was defined as a longitudinal increase on the CDR‐sum of boxes and/or FAQ. For CN/SMC, conversion from normal cognition to MCI was also assessed. ROC curves were calculated for each objective and subjective measure for predicting conversion, functional decline, MMSE decline, and A/T/N positivity.ResultsFigure 1 shows ROC curves for the best predictor of each outcome. Baseline Aβ positivity, MCI conversion, and MMSE decline were best predicted by RAVLT immediate recall. However, functional decline and N positivity were best predicted by the CCI‐12. Tau positivity was also best predicted by subjective memory, the ECog memory sub‐score.ConclusionObjective memory provided the best prediction of Aβ positivity, MCI conversion, and cognitive decline, while subjective memory was the best predictor of T and N positivity and functional decline. These findings suggest that objective and subjective performance provide complementary information about prognosis in preclinical and very mild symptomatic individuals. Future evaluations of prognostication of these measures in a clinical setting will expand these findings.