Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from 18FFDG PET Voxel-Wise Analysis

• Published in: Journal of Alzheimer's disease 2024-01, Vol.101 (2), p.475
• Main Authors: Kreshpa, Wendy, Raffa, Stefano, Girtler, Nicola, Brugnolo, Andrea, Mattioli, Pietro, Orso, Beatrice, Calizzano, Francesco, Arnaldi, Dario, Peira, Enrico, Chincarini, Andrea, Tagliafico, Luca, Monacelli, Fiammetta, Calcagno, Pietro, Serafini, Gianluca, Gotta, Fabio, Mandich, Paola, Pretta, Stefano, Del Sette, Massimo, Sofia, Luca, Sambuceti, Gianmario, Morbelli, Silvia, Schenone, Angelo, Massa, Federico, Pardini, Matteo
• Format: Article
• Language: English
• ISSN: 1875-8908; 1875-8908
• DOI: 10.3233/JAD-240430

Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated.BackgroundDiscrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated.To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI.ObjectiveTo explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI.We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC).MethodsWe retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC).DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AE