After having obtained ethical approval, we commenced and are now in an advanced phase of the recruitment of patients and healthy controls (HC), in whom we are performing cognitive and personality testing (behavioural data) and collecting structural and functional MRI (fMRI) data.
Preliminary correlation and regression analyses have been performed on the behavioural data so far collected from patients and HC to relate premorbid personality and cognitive reserve to anosognosia and delusions. We found that AD patients with anosognosia have a lower premorbid tendency to reflectiveness and lower cognitive reserve. This preliminary result supports the hypothesis proposed in UnaWireD: Individuals who, in the course of their life, have engaged in more reflective thinking seem to demonstrate greater awareness of their cognitive impairment, therefore reflection has a potentially protective role against anosognosia in individuals with AD.
Resting-state fMRI (rsfMRI) data collected so far have been preprocessed using independent component analysis at the single subject level. Task-based fMRI data collected so far have also been preprocessed and analysed at the single-subject level. Preliminary fMRI group analyses have been performed in the HC group only to compare results with literature concerning error monitoring and self-reflection. Comparisons between patients with/without anosognosia and/or delusions relative to HC will be performed when we have reached a minimum sample size of 15 patients for each group with/without each symptom. The preliminary analyses performed on data collected so far suggested analysing in a novel way previously collected (before UnaWireD) rsfMRI data to test whether AD patients with anosognosia have an altered balance between the Default Mode Network (DMN) and the Salience Network (SN). We found that anosognosia was associated with a weaker functional connectivity within the DMN and stronger functional connectivity within the SN, suggesting that a dysregulation of the functional connectivity of the DMN and SN may lead to anosognosia. These rsfMRI findings allowed us the publication of peer-reviewed papers.
We also expanded the study of delusions and other behavioural disturbances into previously collected imaging data from patients with frontotemporal dementia, showing that psychotic symptoms, such as delusions, are mainly correlated to functional, rather than structural, brain changes in these patients (this also led to a peer-review publication).
We conducted a review about the brain correlates of anosognosia in Parkinson’s (PD) and Huntington’s Diseases (HD), the two model diseases of dopaminergic imbalance, showing the involvement of regions of the SN and fronto-parietal network to be associated with unawareness in PD patients.
Finally, we analysed structural MRI data to correlate the spatial patterns of Grey Matter Volume (GMV) alterations of aware or unaware AD patients with specific neurotransmitter systems. We found the involvement of serotonin and glutamate receptors in aware patients, and of dopamine transporter and receptors in unaware patients. Although exploratory, these findings confirm the involvement of dopamine in the origin of anosognosia which is one of the main hypotheses of UnaWireD.
