Neuroanatomical and cognitive correlates of domain-specific anosognosia in early Alzheimer's disease

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Decline in self-awareness is a prevalent symptom in Alzheimer’s disease (AD). Current data suggest that an early breakdown in the brain’s default mode network (DMN) is closely associated with the main symptomatic features in AD patients. In parallel, the integrity of the DMN has been shown to be heavily implicated in retained self-awareness abilities in healthy individuals and AD patients. However, the global contribution to awareness skills of other large-scale networks is still poorly understood. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were acquired and pre-processed from 53 early-stage AD individuals. A group-level independent component analysis was run to isolate and reconstruct four intrinsic connectivity large-scale brain functional networks, namely left and right central executive fronto-parietal networks (FPN), salience network, and anterior and posterior DMN. Hypothesis-driven seed-based connectivity analyses were run to clarify the region-specific underpinnings of multi-domain anosognosia. Multiple regression models were run on large-scale network- and seed-based connectivity maps, including scores of memory, non-memory and total anosognosia obtained via the Measurement of Anosognosia Questionnaire. Memory anosognosia scores were associated with selective lower fronto-temporal connectivity and higher parieto-temporal connectivity. Non-memory anosognosia scores were associated with higher connectivity between the anterior DMN and the cerebellum, between the left medial prefrontal seeds and the contralateral prefrontal cortex, and between the left hippocampal seed and the left insula; lower connectivity was observed between the right prefrontal cortex and the right lingual seed. Lastly, total anosognosia scores were associated with large-scale network alterations, namely reduced left-FPN expression in the left posterior cingulate, reduced right-FPN expression in the left inferior lingual gyrus and adjacent inferior occipital cortex, and increased right-FPN expression in the right anterior cingulate. Seed-based analyses yielded significant connectivity differences only in the connectivity pattern associated with the left hippocampal seed by displaying lower intercommunication with the right prefrontal cortex, but higher connectivity with the left caudate nucleus. These findings support the hypothesis that alterations in functional connectivity of frontal lobe regions involved in executive-related mechanisms represent the neural correlates of domain-specific anosognosia in early AD. Up-regulated connectivity with subcortical structures appears to contribute to changes in the network dynamics interplay and fosters the appearance of anosognosia.

Section: Functional Connectivity Associated With Total Anosognosiasupporting

confidence: 45%

Section: Functional Connectivity Associated With Memory Anosognosiamentioning

confidence: 98%

Section: Seed-signal Extraction and Seed-based First Level Analysesmentioning

confidence: 99%

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Altered Interplay Among Large-Scale Brain Functional Networks Modulates Multi-Domain Anosognosia in Early Alzheimer’s Disease

Valera-Bermejo

Marco

Venneri

2022

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“…In summary, reviewing the results of this paper, the ECN involved in frontal and parietal regions showed a downward trend in MCI patients. Areas of the ECN that showed an upward trend are mainly in the occipital, temporal, and subcortical regions with a small portion also rising in the frontal and parietal regions, which may be the compensatory mechanism of the disruption of frontal and parietal lobes in MCI patients (Valera-Bermejo et al, 2020). It is also well-established that the frontal and parietal regions are crucial aspects of the ECN, which send rich sensory information not only for movement controls, but also for other cognitive abilities, especially in executive function (Roh et al, 2020).…”

Section: Special Imaging Abnormal Markersmentioning

confidence: 95%

Functional MRI-Specific Alterations in Executive Control Network in Mild Cognitive Impairment: An ALE Meta-Analysis

Chen

Xue

et al. 2020

Background: Mild cognitive impairment (MCI) is regarded as a transitional stage between normal aging and Alzheimer's disease (AD) dementia. MCI individuals with deficits in executive function are at higher risk for progressing to AD dementia. Currently, there is no consistent result for alterations in the executive control network (ECN) in MCI, which makes early prediction of AD conversion difficult. The aim of the study was to find functional MRI-specific alterations in ECN in MCI patients by expounding on the convergence of brain regions with functional abnormalities in ECN. Methods: We searched PubMed, Embase, and Web of Science to identify neuroimaging studies using methods including the amplitude of low frequency fluctuation/fractional amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in MCI patients. Based on the Activation Likelihood Estimation algorithm, the coordinate-based meta-analysis and functional meta-analytic connectivity modeling were conducted. Results: A total of 25 functional imaging studies with MCI patients were included in a quantitative meta-analysis. By summarizing the included articles, we obtained specific brain region changes, mainly including precuneus, cuneus, lingual gyrus, middle frontal gyrus, posterior cingulate cortex, and cerebellum posterior lobe, in the ECN based on these three methods. The specific abnormal brain regions indicated that there were interactions between the ECN and other networks. Conclusions: This study confirms functional imaging specific abnormal markers in ECN and its interaction with other networks in MCI. It provides novel targets and pathways for individualized and precise interventions to delay the progression of MCI to AD.

“…Similarly, Sapey-Triomphe et al (2015) showed positive associations between volumes of the left ACC and right OFC and proxies of affective processing measured through an emotion recognition task. In early-AD, alterations in the left ACC underpin deterioration in self-awareness ( Amanzio et al, 2011 ; Valera-Bermejo et al, 2020 ), and sustain the creation of complex self-other brain representations ( Amodio and Frith, 2006 ). In addition to the ACC, affective ToM was also associated with the left OFC.…”

Section: Discussionmentioning

confidence: 99%

Large-Scale Functional Networks, Cognition and Brain Structures Supporting Social Cognition and Theory of Mind Performance in Prodromal to Mild Alzheimer’s Disease

Valera-Bermejo

Marco

Mitolo

et al. 2021

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Impairment of social cognition (SC) skills such as recognition and attribution of intentions and affective states of others (Theory of Mind, ToM) has been evidenced in Alzheimer’s Disease (AD). This study investigated the neuropsychological, neuroanatomical and brain-functional underpinnings of SC processing to obtain an understanding of the social neurophenotype in early probable AD. Forty-six patients with mild cognitive impairment and mild probable AD underwent SC assessment including emotion recognition (Ekman-60-faces task) and cognitive and affective ToM (Reading-the-Mind-in-the-Eyes test and Story-based Empathy task). Linear models tested the association between SC scores and neuropsychological measures, grey matter maps and large-scale functional networks activity. The executive domain had the most predominant association with SC scores in the cognitive profile. Grey matter volume of the anterior cingulate, orbitofrontal, temporoparietal junction (TPJ), superior temporal, and cerebellar cortices were associated with ToM. Social cognition scores were associated with lower connectivity of the default-mode network with the prefrontal cortex. The right fronto-parietal network displayed higher inter-network connectivity in the right TPJ and insula while the salience network showed lower inter-network connectivity with the left TPJ and insula. Connectivity coupling alterations of executive-attentional networks may support default mode social-cognitive-associated decline through the recruitment of frontal executive mechanisms.