Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis

Background and Objectives To determine the relative importance of global or regional MRI and blood markers of neu rodegeneration and neuroaxonal injury in predicting cognitive performance for recently di agnosed patients with multiple sclerosis (MS). Methods Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. Results Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. Discussion Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.This work was supported by the European Regional De velopment Fund and the Spanish Ministry of Science, In novation and Universities (grant: RTI2018-096951-A-I00) and the Ministry of Economy and Competitiveness (grant: RYC-2015-18467).Ye