The association between lifelong personality and clinical phenotype in the FTD-ALS spectrum

Giulia Vinceti; Chiara Carbone; Chiara Gallingani; Luigi Fiondella; Simone Salemme; Elisabetta Zucchi; Ilaria Martinelli; Giulia Gianferrari; Manuela Tondelli; Jessica Mandrioli; Annalisa Chiari; Giovanna Zamboni

doi:10.3389/fnins.2023.1248622

The association between lifelong personality and clinical phenotype in the FTD-ALS spectrum

Front Neurosci. 2023 Oct 4:17:1248622. doi: 10.3389/fnins.2023.1248622. eCollection 2023.

Authors

Giulia Vinceti^{1

2}, Chiara Carbone¹, Chiara Gallingani^{1

2}, Luigi Fiondella^{1

2}, Simone Salemme^{1

2}, Elisabetta Zucchi^{1

2}, Ilaria Martinelli^{1

2}, Giulia Gianferrari^{1

2}, Manuela Tondelli^{1

3}, Jessica Mandrioli^{1

2}, Annalisa Chiari², Giovanna Zamboni^{1

2}

Affiliations

¹ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
² Neurology Unit, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
³ Department of Primary Care, Azienda Unità Sanitaria Locale di Modena, Modena, Italy.

Abstract

Introduction: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two phenotypes of the same neurodegenerative disease, the FTD-ALS spectrum. What determines the development of one rather than the other phenotype is still unknown. Based on the clinical observation that patients' personality seems to differ between the two phenotypes, i.e., ALS patients tend to display kind, prosocial behaviors whereas FTD patients tend to present anti-social behaviors, and that these traits are often reported as pre-existing the disease onset by caregivers, we set up to study experimentally patients' personality in their premorbid life.

Methods: We first tested for differences between groups, then tested the association between premorbid personality and current functional organization of the brain. Premorbid personality of a cohort of forty patients, 27 FTD and 13 ALS, was explored through the NEO Personality Inventory 3 (NEO-PI-3), which analyses the five main personality factors, completed by the caregiver with reference to patient's personality 20 years before symptoms onset (premorbid). A subgroup of patients underwent a brain MRI including structural and resting-state functional MRI (rsfMRI).

Results: A significant difference between FTD and ALS in premorbid personality emerged in the Openness (133.92 FTD vs. 149.84 ALS, p = 0.01) and Extraversion (136.55 FTD vs. 150.53 ALS, p = 0.04) factors. This suggests that ALS patients had been, in their premorbid life, more open to new experiences, more sociable and optimistic than FTD patients. They also showed greater functional connectivity than both FTD and a control group in the Salience resting state network, over and above differences in gray matter atrophy. Finally, there was a positive correlation between premorbid Openness and functional connectivity in the Salience network across all patients, suggesting a possible association between premorbid personality and current functional organization of the brain, irrespective of the degree of atrophy.

Discussion: Our proof-of-concept results suggest that premorbid personality may eventually predispose to the development of one, rather than the other, phenotype in the FTD-ALS spectrum.

Keywords: Salience network; amyotrophic lateral sclerosis; disease phenotype; frontotemporal dementia; functional connectivity; personality; premorbid; presymptomatic.

Grants and funding

GZ, SS, MT, EZ, IM, GG, and GV are supported by a grant “Dipartimenti di eccellenza 2018–2022,” MIUR, Italy, to the Department of Biomedical, Metabolic and Neural Sciences, University of Modena. GZ, CC, and AC are supported by a grant funded by the European Union ERC, UnaWireD, project number 101042625.