Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease

Abstract

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting‐state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient‐relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self‐reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self‐reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.

The Petrified Self 10 Years After: Current Evidence for Mnemonic anosognosia

“…A study conducted by Berlingeri et al (2015) found significant functional connectivity reduction in unaware AD patients within the inferior medial temporal cortex (IMTC) and VMPFC networks, but only disconnection between IMTC and hippocampus and insular cortex correlated with anosognosia severity. Finally, a more recent study reported that memory awareness correlated with the degree of disconnection between hippocampus and retrosplenial cortex extending to the ventral PCC and right posterior inferior parietal lobe; in addition, anosognosia was associated with decreased connectivity between hippocampus and VMPFC (Antoine et al, 2019).…”

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

“…According to this view, reduced connectivity of the default mode network (DMN), seen in the early phases of AD (Klaassens et al, 2017), may act as a marker of progression associated with anosognosia (Therriault et al, 2018). In fact, the bases of impaired selfawareness and anosognosia have been heavily intertwined to the functionality of the DMN in AD (Antoine et al, 2019;Mondragon, Maurits & Deyn, 2019) and other neurological conditions, such as anosognosia for hemiplegia (Pacella et al, 2019). On these grounds, the DMN could be conceived as a translational construct to justify a routine assessment in the preclinical stage of AD (Cacciamani et al, 2017).…”

Anosognosia in Mild Cognitive Impairment: Lack of Awareness of Memory Difficulties Characterizes Prodromal Alzheimer's Disease

“…Several of these regions belong to the Default Mode Network (DMN), which supports cognitive processing of the self and autobiographical memory (50). Accordingly, lack of awareness in AD is also associated with decreased functional connectivity between brain areas within the DMN or between DMN and other brain regions (51)(52)(53)(54). Interpreted at the light of the Cognitive Awareness Model, the neural correlates of anosognosia in AD suggest that several difficulties can explain lack of awareness for memory deficits in the patients.…”

“…Interpreted at the light of the Cognitive Awareness Model, the neural correlates of anosognosia in AD suggest that several difficulties can explain lack of awareness for memory deficits in the patients. Decreased connectivity between frontal, temporal, and parietal areas on the one hand and medial temporal lobe regions on the other hand would contribute to failure of updating the personal knowledge base; medial prefrontal and posterior cingulate damage would affect the efficacy of self-referential processing during explicit performance evaluation; and deficient error monitoring caused by damage to the anterior cingulate cortex and insula would disturb comparator mechanisms ( 51 , 55 ).…”