Cognitive impairment in multiple sclerosis: Where do we stand today?

Background: The therapeutic landscape of multiple sclerosis (MS) has evolved substantially with earlier diagnosis and increasing use of highly effective disease-modifying therapies, leading to marked reductions in relapse activity and delayed disability progression. Despite these advances, cognitive impairment remains highly prevalent. Objective: This topical review summarises current evidence on cognitive impairment in MS, from the earliest and preclinical stages to paediatric and ageing populations. Results: Particular emphasis is placed on emerging data-driven cognitive phenotypes, which capture the multidimensional nature of cognitive dysfunction and link distinct cognitive profiles to specific neuroimaging substrates. The review also discusses key neurobiological mechanisms underlying cognitive decline, including grey matter pathology, network dysfunction and synaptic alterations, as well as cognitive progression independent of relapse activity. Conclusions: Cognitive impairment represents a major source of disability. Implications for cognitive monitoring and management are considered, highlighting cognition as a core outcome and therapeutic target in contemporary MS care.