Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;101(2):475-485.
doi: 10.3233/JAD-240430.

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

Wendy Kreshpa  1 , Stefano Raffa  2   3 , Nicola Girtler  1   2 , Andrea Brugnolo  1   2 , Pietro Mattioli  1   2 , Beatrice Orso  1 , Francesco Calizzano  1 , Dario Arnaldi  1   2 , Enrico Peira  4 , Andrea Chincarini  4 , Luca Tagliafico  2   5 , Fiammetta Monacelli  2   5 , Pietro Calcagno  1   2 , Gianluca Serafini  1   2 , Fabio Gotta  1   2 , Paola Mandich  1   2 , Stefano Pretta  2 , Massimo Del Sette  2 , Luca Sofia  3 , Gianmario Sambuceti  2   3 , Silvia Morbelli  6   7 , Angelo Schenone  1   2 , Federico Massa  1   2 , Matteo Pardini  1   2 ; Dementia Disease Management Team of the IRCCS Ospedale Policlinico San Martino, Genoa
Collaborators, Affiliations

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

Wendy Kreshpa et al. J Alzheimers Dis. 2024.

Abstract

Background: 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.

Objective: 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.

Methods: 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).

Results: 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-AES VOI with the right cingulate gyrus and its anterior projections compared to HC.

Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

Keywords: Alzheimer’s disease; [18F]FDG PET; apathy; awareness; dementia; mild cognitive impairment.

PubMed Disclaimer

MeSH terms

Substances

LinkOut - more resources