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

Article type: Research Article

Authors: Grisanti, Stefano Giuseppe^{a; 1} | Massa, Federico^{a; 1; *} | Chincarini, Andrea^b | Pretta, Stefano^c | Rissotto, Roberto^c | Serrati, Carlo^d | Monacelli, Fiammetta^{c; e} | Serafini, Gianluca^{a; c} | Calcagno, Pietro^c | Brugnolo, Andrea^{a; c} | Pardini, Matteo^{a; c} | Nobili, Flavio^{a; c; 2} | Girtler, Nicola^{a; c; 2} | Dementia Disease Management Teamof the IRCCS Ospedale Policlinico San Martino, Genoa:

Collaborators: Schenone, Angelo | Nencioni, Alessio | Amore, Mario | Biffa, Gabriella | Sambuceti, Gianmario | Morbelli, Silvia | Roccatagliata, Luca | Castellan, Lucio | Travalca, Cupillo Beatrice | Castellini, Paola | Fiocca, Roberto | Gaggero, Gabriele | Mandich, Paola | Origone, Paola | Livrari, Barbara

Affiliations: [a] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy | [b] Istituto Nazionale di Fisica Nucleare (INFN), Genoa Section, Genoa, Italy | [c] IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [d] Neurology Unit, ASL 1 Hospital, Imperia, Italy; formerly at the Neurology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [e] Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy

Correspondence: [*] Correspondence to: Federico Massa, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] These authors contributed equally as senior authors.

Note: [3] Collaborators of the Dementia Disease Management Team of the IRCCS Ospedale Policlinico San Martino, Genoa, Italy: Angelo Schenone, Alessio Nencioni, Mario Amore, Gabriella Biffa, Gianmario Sambuceti, Silvia Morbelli, Luca Roccatagliata, Lucio Castellan, Beatrice Travalca Cupillo, Paola Castellini, Roberto Fiocca, Gabriele Gaggero, Paola Mandich, Paola Origone, Barbara Livrari.

Abstract: 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.

Keywords: Alzheimer’s disease, apathy, awareness, dementia discrepancy, mild cognitive impairment

DOI: 10.3233/JAD-220418

Journal: Journal of Alzheimer's Disease, vol. 93, no. 1, pp. 75-86, 2023