Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases which manifest with behavioral, cognitive, and language disorders, and with a progressive paralysis of voluntary muscles, respectively. Recently, common genetic and neuropathological grounds have been found between the two diseases, so that they are now recognized as part of the same neurodegenerative continuum (FTD-ALS spectrum). Patients can present with pure behavioral/cognitive (FTD) or motor (ALS) phenotypes or, even more commonly, with mixed forms (FTD-ALS). Factors determining the development of the specific phenotype are currently unknown. However, it is a common clinical observation that patients’ personality differs between the phenotypes: ALS patients often display a nice and pleasant attitude, while FTD patients typically exhibit antisocial behaviors and lack of empathy. These tracts are often described by patients’ caregivers as already present before the disease onset, having always characterized patients’ personality.
The aim of the study presented in this thesis was to investigate whether FTD and ALS patients differ in their premorbid personalities and, consequently, in the brain correlates associated with personality traits. We hypothesized that such differences, if present, might be contributing factors to the development of a behavioral rather than motor (or vice versa) phenotype in the spectrum FTD-ALS.
Consecutive FTD and/or ALS patients who presented to Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria Modena, were recruited between December 2018 and April 2021. Assessment of current and premorbid personality was performed through the NEO Personality Inventory 3 (NEO-PI-3), a questionnaire which analyze the five principal dimensions of personality (Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness). T1-weighted MRI images were also obtained, to perform a correlation analysis between gray matter (GM) volume and personality traits through voxel-based morphometry (VBM).
Forty-eight patients were recruited and underwent NEO-PI-3 and neuropsychological assessment. Among them, 20 also underwent MRI scanning. A significant difference in premorbid personality between groups emerged in the Extraversion and Openness domains. As per caregivers-based questionnaires regarding the premorbid state, patients with motor phenotype (ALS) were more prosocial and friendly, and were more predisposed to new experiences, emotions, ideas, than patients with dementia (FTD). At current time, the difference in Openness persisted at a significant level, and differences were also found in the Agreeableness and Conscientiousness domains. The VBM analysis across all 20 subjects undergoing MRI showed a positive correlation between premorbid Neuroticism and GM volume in the areas of left hippocampus, left parahippocampal gyrus, and left and right nucleus accumbens.
The results confirm the initial hypothesis of a significant difference between FTD and ALS patients’ premorbid personalities (Extraversion and Openness domains), supporting the idea that personality traits could represent a marker of vulnerability to the development of cognitive/behavioral versus motor phenotypes in the FTD-ALS spectrum. These significant behavioral findings were not reflected on significant differences in brain anatomy on the VBM analysis, probably due to low sample size of patients undergoing MRI.