Bridging cognitive gaps: development of novel diagnostic criteria for MCI in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by both inflammatory and neurodegenerative processes, predominantly affecting young adults. Cognitive impairment is a common but often underrecognized symptom of MS, affecting approximately 40% to 70% of patients. This impairment significantly reduces personal autonomy, limits work performance, and hinders active social participation, underscoring the need for early identification and effective management strategies. This PhD thesis aims to develop and validate specific diagnostic criteria for Mild Cognitive Impairment (MCI) tailored to the MS population (MS-MCI). Additionally, it seeks to characterize the cognitive impairments associated with MS, identify specific cognitive patterns and predictors, and investigate the role of mood, fatigue, cognitive reserve, and self-perception of cognitive difficulties in determining the MS-MCI diagnosis. A comprehensive neuropsychological assessment was conducted on a cohort of 229 MS patients, encompassing tests across multiple cognitive domains, including memory, attention, executive functions, language, and visuospatial abilities. Self-report questionnaires assessing fatigue, mood, cognitive reserve, and cognitive self-perception were also administered. Statistical analyses were performed to validate the MS-MCI criteria and to identify cognitive patterns and significant predictors of cognitive impairment. The findings demonstrated the utility and sensitivity of the newly developed MS-MCI criteria in capturing the nuanced spectrum of cognitive impairment among individuals with MS. A higher prevalence of cognitive impairment was revealed compared to previous reports, with impairments spanning language, memory, attention, executive functions, and visuospatial abilities. Notably, language functions emerged as particularly vulnerable, highlighting the necessity of including language-specific assessments in standard MS evaluations. Age and physical disability, as measured by the Expanded Disability Status Scale (EDSS), emerged as significant predictors of cognitive impairment, reinforcing the impact of aging and disability on cognitive health in MS. In contrast, cognitive reserve did not exhibit a protective effect against cognitive impairment, suggesting that disease-specific neuropathology may overshadow these influences in MS. Furthermore, mood and fatigue were not significantly associated with cognitive impairment, challenging assumptions about their direct link to cognitive decline in MS and indicating the need for a more nuanced understanding of how these symptoms interact with cognitive function. This study underscores the clinical value of applying a comprehensive, multidomain neuropsychological battery for assessing cognitive impairment in MS and provides strong support for the adoption of MS-MCI criteria in routine clinical practice. The high concordance between clinical and statistical MS-MCI diagnoses suggests that an integrated approach, combining clinical judgment with statistical analysis, offers the most accurate and sensitive identification of cognitive impairment. In conclusion, this research highlights the importance of a nuanced, multidimensional assessment of cognitive impairment in MS. By refining diagnostic criteria and expanding cognitive evaluation protocols to include domains traditionally underrepresented in MS assessments, clinicians and researchers can improve diagnostic accuracy, facilitate timely intervention, and enhance the overall management of cognitive health in MS. This approach holds the potential to significantly improve the quality of life for individuals with MS by addressing cognitive concerns as effectively as physical symptoms, paving the way for a more personalized model of MS care.