Multiple sclerosis (MS) is a complex neurological condition primarily known for its effects on physical movement and coordination. However, research over recent decades has increasingly highlighted that MS also significantly impacts cognitive function, leading to what is often called cognitive decline. This cognitive decline in MS is a multifaceted phenomenon involving various mental processes such as memory, attention, information processing speed, and executive functions. Understanding the research on MS and cognitive decline requires exploring how cognitive impairment manifests in MS, the underlying brain changes, the variability among patients, and the emerging tools and approaches to assess and manage these cognitive challenges.
Cognitive decline in MS is surprisingly common, affecting between 40% and 70% of people with the disease. The cognitive domains most frequently impaired include information processing speed, working memory, sustained attention, and sometimes memory encoding. These impairments can occur even when physical symptoms are mild or absent, which means cognitive problems may go unnoticed or untreated in many patients. This has led researchers to identify a subtype of MS characterized predominantly by cognitive deficits with minimal motor impairment, sometimes called a “cognition-first” subtype. This subtype challenges traditional views of MS, which have focused heavily on physical disability, and underscores the need for routine cognitive assessments throughout the disease course.
The neural mechanisms behind cognitive decline in MS are complex and not yet fully understood. MS causes damage to the central nervous system by attacking the myelin sheath that insulates nerve fibers, leading to lesions and brain atrophy. These structural changes disrupt the brain’s communication networks, which are crucial for cognitive functions. Studies using advanced brain imaging techniques, such as magnetic resonance imaging (MRI), have shown that the integrity of resting state functional connectivity (RSFC) networks in the brain correlates with cognitive performance in MS patients. For example, better cognitive test scores are associated with stronger connectivity in sensorimotor, frontoparietal, salience, and visual networks. However, this relationship is altered in the presence of mild cognitive impairment, suggesting that as MS progresses, the brain’s ability to maintain functional connectivity diminishes, contributing to cognitive decline.
One of the challenges in studying cognitive decline in MS is the variability in how it presents and progresses. Some patients experience stable cognitive function over time, especially in pediatric MS cases, while others show gradual decline. This variability may depend on factors such as disease duration, lesion location, brain atrophy, and individual differences in brain plasticity and reserve. Cognitive impairment can also fluctuate with relapses or periods of inflammation, adding another layer of complexity to understanding and managing these symptoms.
Given the high prevalence and impact of cognitive decline in MS, there has been a push to develop practical and scalable methods for cognitive assessment. Traditional neuropsychological testing, while comprehensive, is time-consuming and not always feasible in routine clinical practice. Recent research has validated online cognitive assessment platforms designed specifically for MS patients. These tools can be used remotely and unsupervised, allowing for frequent monitoring of cognitive function. One such platform, Cognitron-MS, includes a battery of tasks sensitive to the cognitive domains affected by MS and has been shown to reliably detect cognitive deficits. This approach facilitates early identification of cognitive problems and helps prioritize patients for more detailed neuropsychological evaluation and intervention.
The recognition of cognitive decline as a core feature of MS has important implications for patient care. Cognitive impairment can affect daily functioning, employment, social relationships, and quality of life. Despite this, cognitive symptoms are often under-recognized and under-treated. Incorporating routine cognitive screening into MS management can help clinicians tailor treatments and support services to address these challenges. Cognitive rehabilitation, pharmacological interventions, and lifestyle modifications such as physical exercise and cognitive training are areas of ongoing research aimed at mitigating cognitive decline in MS.
In summary, research on MS and cognitive decline reveals that cognitive impairment is a prevalent and impactful aspect of the disease, sometimes occurring independently of physical disability. Advances in brain imaging have illuminated the neural disruptions underlying cognitive problems, while innovative assessment tools are making i
