A multimodal approach to the study of self and others’ awareness in prodromal to mild Alzheimer’s disease

Patients in the early stage of Alzheimer’s disease (AD) can manifest disorders of cognitive awareness such as a lack of/limited self-awareness of their own cognitive deficits (anosognosia) or as a reduction in the ability to be aware of others, i.e., social cognition; more specifically in the ability to recognise emotions or attribute mental states to others (also known as Theory of Mind, ToM). The present thesis intended to explain the behavioural, brain neuroanatomical, structural connectivity and resting-state functional relationship between the presence of multi-domain alterations of self-awareness/anosognosia and others awareness/social cognition to understand the cognitive and neural substrates that shape conscious awareness in early AD. Behavioural findings evidenced an association between the presence of anosognosia and reduced ToM. Individually, memory anosognosia was associated with memory proxies and total anosognosia with visuospatial abilities, while social cognition was associated with language, memory, attention and most importantly, executive functions. Neuroanatomical structural findings of non-memory and total anosognosia showed reduced grey matter volume in the anterior cingulate cortex (ACC), fusiform, lingual and precentral gyri. Conversely, ToM showed reduced grey matter volume also in the ACC, but reduction extended to encompass temporoparietal junction, orbitofrontal, superior temporal and cerebellar cortices. The ACC showed a statistical shared neural overlap between self-other awareness. At the functional level, both anosognosia and social cognition were associated with reduced internetwork connectivity between the default mode network (DMN) and the executive frontoparietal network (FPN), as well as higher connectivity between the DMN and the salience network, in which the insula seems to have an essential role. Subcortical contributions to large-scale network connectivity were also found. We propose that medial frontal executive mechanisms, such as those subserved by the ACC, might support awareness in the presence of an inherently damaged DMN in early-AD. Functional adaptive reorganisation of network dynamics might increase the strain to salient system hubs (ACC) by redirecting network traffic of executive resources to cope with the progressive decline of conscious awareness