Discrepancy Between Patient and Caregiver Estimate of Apathy Predicts Dementia in Patients with Amnestic Mild Cognitive Impairment

Background: Apathy is a frequent behavioral symptom of Alzheimer's disease (AD). The Apathy Evaluation Scale (AES) is a tool exploring the perception of apathy by both caregivers (CG-AES) and patients (PT-AES), and the discrepancy in their ratings is a proxy of patients' disease unawareness. Objective: To assess in a cohort study of patients with amnesic mild cognitive impairment (aMCI) whether apathy and awareness of apathy predict progression to dementia and timing. Methods: From the global AES scores of 110 patients with aMCI and their caregivers, we obtained two principal indices for analysis: 1) 'Apathy', the mean of PT-AES and CG-AES, and 2) 'Discrepancy', obtained by subtracting CG-AES from PT-AES. Patients were followed with visits every six months for three years or until dementia. AES indices and the principal demographical/neuropsychological variables were filtered from multicollinearity. The most robust variables entered a logistic regression model and survival analyses (Cox regression, log-rank test of Kaplan-Meier curves) to estimate which predicted the risk and timing of progression, respectively. Results: Sixty patients (54.5%) developed dementia (57 AD) after 6.0-36.0 months, 22 (20%) remained in an MCI stage, and 28 (25.5%) dropped out. 'Discrepancy' was a robust and accurate predictor of the risk of progression (AUC = 0.73) and, after binarization according to a computed cutoff, of timing to dementia. Conclusion: A structured evaluation of apathy, both self-assessed and estimated by caregivers, can provide useful information on the risk and timing of progression from aMCI to dementia. The discrepancy between the two estimates is a fairly reliable index for prediction purposes as a proxy of disease unawareness.