Cognitive alterations in Multiple Sclerosis patients: diagnostic, prognostic, and rehabilitation aspects

Cognitive impairment is frequent in most patients with Multiple Sclerosis (MS) and affects several cognitive domains, having a significant impact on their quality of life and on their personal, social and work dimensions. An early and comprehensive neuropsychological assessment may provide relevant diagnostic, prognostic, and rehabilitative implications. The first chapter highlights the diagnostic and the prognostic aspects, with the description of a multicentric project, conducted in collaboration with MS centers of Bergamo, Montichiari, and Modena, in which were included newly-diagnosed MS patients and were evaluated their neurological, neuropsychological, neuroradiological and bioumoral outcomes. Results of this project have allowed the preparation of several sub-studies with important results: the first study highlighted how MS patients at the time of diagnosis, even in the absence of an evident cognitive impairment as clinically defined, are characterized by slight cognitive alterations as compared to healthy controls, both considering global cognitive functioning level and also specific cognitive domains. The second study has allowed the identification of two biomarkers present in the cerebrospinal fluid that are associated with cognitive alterations: the first (LIGHT) is associated with the inflammatory phase of the disease, while the second (parvalbumin) is associated with the neurodegenerative phase of the disease and also correlates with cortical thinning and physical disability, moreover with a stronger association compared to the one found with the level of neurofilament light chain (NF-L, a well-known biomarker of neurodegeneration). The third study has allowed to describe the predictive role of some inflammatory cytokines in the cerebrospinal fluid (CXCL13, CXCL12, IFNγ, TNF, TWEAK, LIGHT, sCD163) in discriminating, since the time of diagnosis, those MS patients that were more likely to develop neurologic and neuroradiologic worsening after 4-years follow-up. The second chapter addresses the importance of assessing MS patients not only with the classical neuropsychological tests but also with experimental paradigms. The first study, conducted in collaboration with the University of Florence and the University of Padua, investigated the phenomena of false memories, using a paradigm that induces memory distortions due to the strong connection between words associated with a same semantic category. Results showed that MS patients were not characterized by the expected memory distortions, probably due to weak association between nodes that compose semantic memory, because of neurodegenerative events. The second study, conducted in collaboration with the Kessler Foundation (West Orange, NJ, USA), focused on social cognition abilities: in a group of MS patients without evidence of cognitive impairment as traditionally defined was observed a performance significantly lower compared to healthy controls in tests of facial emotion recognition, theory of mind, and empathy. Moreover, it was demonstrated that these social cognition alterations were correlated specifically with the cortical lesions volume in both the amygdalae of MS patients, while no significant correlation was found with other measures of brain damage included in the study (cortical thickness and cortical lesion load in all the cerebral cortex). The third and last chapter focuses on the rehabilitative aspects, showing results from a study carried at the Buffalo Neuroimaging Analysis Center (Buffalo, NY, USA) on a group of MS patients that performed a cognitive training by using a telerehabilitation approach. The project aimed to identify neurological, psychological and neuroradiological variables able to characterize patients that can benefit more from the rehabilitation. Results showed that a relapsing-remitting disease phenotype (as compared with progressive patients), a higher personality trait of conscientiousness, a higher gray matter volume, a lower tract disruption in a network centered on precuneus and posterior cingulate, and a higher deviation in functional brain connectivity compared to healthy controls, play a key role to achieve a greater cognitive amelioration after the rehabilitative treatment.