The Role of Hub and Spoke Regions in Theory of Mind in Early Alzheimer’s Disease and Frontotemporal Dementia

Abstract

Theory of mind (ToM, the ability to attribute mental states to others) deficit is a frequent finding in neurodegenerative conditions, mediated by a diffuse brain network confirmed by 18F-FDG-PET and MR imaging, involving frontal, temporal and parietal areas. However, the role of hubs and spokes network regions in ToM performance, and their respective damage, is still unclear. To study this mechanism, we combined ToM testing with brain 18F-FDG-PET imaging in 25 subjects with mild cognitive impairment due to Alzheimer’s disease (MCI–AD), 24 subjects with the behavioral variant of frontotemporal dementia (bvFTD) and 40 controls. Regions included in the ToM network were divided into hubs and spokes based on their structural connectivity and distribution of hypometabolism. The hubs of the ToM network were identified in frontal regions in both bvFTD and MCI–AD patients. A mediation analysis revealed that the impact of spokes damage on ToM performance was mediated by the integrity of hubs (p < 0.001), while the impact of hubs damage on ToM performance was independent from the integrity of spokes (p < 0.001). Our findings support the theory that a key role is played by the hubs in ToM deficits, suggesting that hubs could represent a final common pathway leading from the damage of spoke regions to clinical deficits.

Theory of mind in patients with mild cognitive impairment: A systematic review

“…In the end, also the most recent study of the present review (Orso et al, 2022 ), agrees with the previous studies. In fact, it is reported that MCI-AD patients ( n = 25) showed a poorer performance in the RMET compared to HC ( n = 40).…”

“…Different research showed that TOM can be impaired in several neurodegenerative disorders, such as in Alzheimer's Disease (as reported by Morese et al, 2018;Kessels et al, 2021;Morese and Palermo, 2022), Parkinson's Disease (Rossetto et al, 2018;Adenzato et al, 2019;Morese and Palermo, 2020), Frontotemporal Dementia-behavioral variant (Adenzato et al, 2010;Poletti et al, 2012;Orso et al, 2022), but also in cognitive disorders without dementia, such as Mild Cognitive Impairment (MCI). In this regard, several studies reported lower performance in many TOM tasks in MCI patients, compared to healthy populations (Baglio et al, 2012;Poletti and Bonuccelli, 2013;Moreau et al, 2015;Adenzato et al, 2019;Orso et al, 2022).…”

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

“…The age-related impairments in the ability to process contextual information and in the regulation of responses to threat are related to structural and physiological alterations in the PFC and medial temporal lobe [ 177 ]. Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose has shown the deficit of hubs in the theory of mind network in patients with mild cognitive impairment due to AD [ 178 ]. Brain autopsy and imaging studies reveal the atrophy of the brain including the frontal, temporal, parietal, entorhinal cortices, amygdala, and hippocampus [ 179 ].…”

Analyzing of Alzheimer’s Disease Based on Biomedical and Socio-Economic Approach Using Molecular Communication, Artificial Neural Network, and Random Forest Models

“…There are also studies about risk factors, pathogenesis, and structural and functional changes associated with neurodegeneration in AD [32][33][34], the genetic, clinical, and biochemical data of individual patients [35], searching for peripheral biomarkers in neurodegenerative diseases [36] and gut microbiota regulation and their implication in the development of neurodegenerative disease [37,38]. In [39], the pathophysiological basis and biomarkers of AD pathology, and molecular signs of neural inflammation in neurodegenerative diseases are investigated. In [39,40], the roles of hub and spoke regions in theory of mind in early AD and frontotemporal dementia are studied.…”

“…In [39], the pathophysiological basis and biomarkers of AD pathology, and molecular signs of neural inflammation in neurodegenerative diseases are investigated. In [39,40], the roles of hub and spoke regions in theory of mind in early AD and frontotemporal dementia are studied. In [40], the etiological factors behind neurodegenerative disease are explored.…”