Cognitive Impairment in Newly Diagnosed Patients with Multiple Sclerosis: A Systematic Review of Related Molecular Biomarkers and a Meta-Analysis of Associated Demographic and Disease-Related Characteristics.

: Neuropsychological impairment (NI) is common in newly diagnosed patients with multiple sclerosis (pwMS). This study has two main objectives; the systematic review aims to describe the relationship between NI and molecular biomarkers in newly diagnosed pwMS, and the meta-analysis aims to explore the relationship between NI, age, disability status, and disease duration in this patient group. : We conducted a systematic review, with 20 studies meeting the inclusion criteria. Out of these, 12 studies were included in the meta-analysis. We analyzed three key cognitive measures-the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), and the Selective Reminding Test-long-term storage (SRT-LTS)-in relation to demographic and MS-related characteristics. : Neurofilament light chain (NfL) levels were consistently associated with NI, especially a slower information processing speed (IPS). Other biomarkers, including chitinase 3-like 1 (CHI3L1), brain-derived neurotrophic factor (BDNF), apolipoprotein E4 allele (APOE4), and vitamin D, also showed promising correlations with NI. A meta-regression analysis of 2380 pwMS indicated a negative association between SDMT score and disability status ( = 0.01). No significant associations were found for the PASAT with age, disability status, or disease duration ( > 0.05). : These findings highlight the role of NfL as a biomarker related to NI in newly diagnosed pwMS and the association between IPS and disability status. Further research is needed with more homogeneous samples in terms of the disease duration, along with standardized cognitive assessments and a broader range of biomarkers, to improve our understanding and management of cognitive difficulties in the early stages of MS.