Vinceti Giulia, Carbone Chiara, Gallingani Chiara, Fiondella Luigi, Salemme Simone, Zucchi Elisabetta, Martinelli Ilaria, Gianferrari Giulia, Tondelli Manuela, Mandrioli Jessica, Chiari Annalisa, Zamboni Giovanna
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Neurology Unit, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Front Neurosci. 2023 Oct 4;17:1248622. doi: 10.3389/fnins.2023.1248622. eCollection 2023.
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.
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).
A significant difference between FTD and ALS in premorbid personality emerged in the Openness (133.92 FTD vs. 149.84 ALS, = 0.01) and Extraversion (136.55 FTD vs. 150.53 ALS, = 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.
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.
额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）是同一神经退行性疾病——FTD-ALS谱系的两种表型。决定出现其中一种而非另一种表型的因素仍不清楚。基于临床观察，即两种表型患者的性格似乎有所不同，也就是说，ALS患者往往表现出善良、亲社会行为，而FTD患者往往表现出反社会行为，且照顾者常报告这些特质在疾病发作前就已存在，我们着手对患者病前生活中的性格进行实验研究。
我们首先测试组间差异，然后测试病前性格与当前大脑功能组织之间的关联。通过“大五人格量表第三版”（NEO-PI-3）对40名患者（27名FTD患者和13名ALS患者）的病前性格进行探究，该量表分析五个主要人格因素，由照顾者参照患者症状出现前20年（病前）的性格完成填写。一组患者接受了脑部MRI检查，包括结构和静息态功能MRI（rsfMRI）。
FTD和ALS患者在病前性格的开放性（FTD为133.92，ALS为149.84，P = 0.01）和外向性（FTD为136.55，ALS为150.53，P = 0.04）因素上出现显著差异。这表明，在病前生活中，ALS患者比FTD患者对新体验更开放、更善于社交且更乐观。在显著性静息态网络中，他们还表现出比FTD患者和对照组更强的功能连接性，超过了灰质萎缩方面的差异。最后，所有患者的病前开放性与显著性网络中的功能连接性之间存在正相关，这表明病前性格与当前大脑功能组织之间可能存在关联，与萎缩程度无关。
我们的概念验证结果表明，病前性格最终可能使个体在FTD-ALS谱系中更容易发展出一种而非另一种表型。
