Phd in PHD PROGRAM IN BEHAVIORAL NEUROSCIENCE

Thesis title: Gaucher Disease: A multidisciplinary study of Neuropsychology, Neurology, and Advanced Neuroimaging Techniques for a Comprehensive Understanding

Introduction Gaucher disease (GD) is a rare autosomal recessive genetic disorder caused by deficiency of the enzyme glucocerebrosidase, which leads to the accumulation of glucosylceramide in macrophages. There are five known types of GD: type 1 (chronic non-neurological), type 2 (acute neurological), type 3 (subacute neurological), perinatal lethal and cardiovascular. Mutations in the GBA1 gene cause all forms of Gaucher disease, leading to lysosomal deficiency of glucocerebrosidase activity. In types 2 and 3 of Gaucher disease, neurological symptoms are prominent and may include developmental delays, seizures, ataxia, and cognitive decline. Patients with Gaucher disease (GD) have numerous brain changes. Objectives The main objective is to investigate the neuropsychological and psychological profile of Italian GD1 and GD3 patients at baseline (T0) compared with healthy individuals. In addition, it aims to investigate possible worsening at a second neuropsychological, psychological, and neurological assessment (T1). Moreover, the study aims to explore possible correlations between neuroimaging and the neuropsychological and neurological aspects of GD. Materials and Methods. In this longitudinal observational study, we recruited patients with a confirmed genetic diagnosis of Gaucher disease (GD), older than 12 years, at AOU Policlinico Umberto. Main cognitive functions were analyzed with neuropsychological tests at T0 and T1. The psychological status of patients at both T0 and T1 was assessed with psychometric instruments. A neurological evaluation was conducted at T0 and T1. In addition, possible brain alterations were explored using imaging by DTI technique to correlate brain fiber connectivity with data from neuropsychological and neurological assessments. Results Neuropsychological tests revealed significant differences in cognitive function between GD patients and in healthy patients. At T1, 17 patients completed a full neuropsychological evaluation, revealing an increased prevalence of cognitive impairment (64.7% vs. 31.8% at baseline). The most affected cognitive functions are verbal memory and attention. Diffusion Tensor Imaging (DTI) revealed alterations in associated brain fiber connectivity in correlation with neuropsychological and neurological assessments. Conclusions In conclusion, the results highlight the importance of a multidisciplinary approach in the management of the disease and that the use of advanced neuroimaging techniques is crucial to identifying brain alterations and understanding their impact on cognitive and neurological function.