Abstract
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.
Highlights
Anosognosia in Alzheimer’s disease (AD) is a prevalent symptom that can be defined as the inability of a patient to recognize decline in their own cognitive functioning (Hanseeuw et al, 2020)
Along the same directional lines, positive associations were found between non-memory anosognosia scores and anterior DMN (aDMN) expression in the cerebellar culmen, bilaterally (k = 263, p = 0.038), and between total anosognosia and aDMN expression in the right anterior cingulate (k = 261, p = 0.039; Table 2 and Figure 3)
Awareness of symptoms within the non-memory domain was positively linked to connectivity between the aDMN and cerebellum, between left hippocampus and left insula and between left medioprefrontal and right dorsolateral prefrontal cortex
Summary
Anosognosia in Alzheimer’s disease (AD) is a prevalent symptom that can be defined as the inability of a patient to recognize decline in their own cognitive functioning (Hanseeuw et al, 2020). Anosognosia might not manifest only as lack of awareness of a memory impairment but can apply to other cognitive domains, such as unawareness of executive dysfunction, of socio-emotional deficits or of difficulties with daily life activities (Lacerda et al, 2021). This heterogeneity highlights the multidimensionality of this phenomenon and warrants the necessity for a multidomain clinical assessment (Leicht et al, 2010; de Ruijter et al, 2020). AD patients with alterations affecting the DMN might have difficulties with self-awareness or may manifest anosognosia very early in the course of the disease
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