Cognitive impairment in individuals with MS has been reported for almost 150 years  The aspects of such cognitive impairment are multifaceted, affecting multiple domains including attention, information processing speed (IPS), memory, and executive control . Such changes in cognition have been shown to have a deleterious effect on quality of life. Cognitive impairment has been shown to occur at both early and later stages of the disease  becoming more prevalent in the advanced stages, suggesting long-term deleterious effects on individuals of all ages with MS.
Several recent publications have sought to continue to increase our knowledge around cognitive impairment in individuals with MS, attempting to identify brain lesions that may underlie this symptom of the disease. Factors that might influence the impact of cognitive impairment on daily life for individuals with MS have also been examined.
The impact of cognitive impairment in individuals with MS
Although the physical impairment associated with MS can be the principal factor affecting an individual’s daily life, the impact of cognitive impairment has been shown to be similar for all levels of disability . Cognitive impairment in individuals with MS can detrimentally affect many aspects of daily life , for example the ability to run a household, maintain a social life, and sustain productivity at work; together, these factors can all impair overall quality of life.
Interestingly, educational level has been noted to be a protective factor against cognitive impairment in individuals with MS. A study involving 136 individuals with MS and 65 healthy controls stratified participants according to their level of education  and applied a battery of neuropsychological tests. In this study, worse cognition was observed among those individuals with low education levels, higher T2 lesion load, and male gender. In addition, the impact of a higher level of education was most pronounced in individuals with less than 5 years of MS disease duration, suggesting a stronger role of cognitive reserve in short-term disease, while a greater impact of increased inflammatory activity on cognition was seen in long-term MS. These findings were supported by a second study that analysed short-term memory, logical memory, and verbal fluency in 65 individuals with MS and concluded that educational achievement or level was a protective factor against cognitive impairment . Pre-diagnostic educational attainment was also demonstrated to be predictive of job retention  in a sample of 1,126 individuals who were employed at the time of receiving their diagnosis of MS. A further study in 124 individuals with relapsing-remitting MS noted that level of executive cognitive functioning could moderately predict a deterioration in employment status  over a period of 2 years.
Structural and functional changes underlying cognitive impairment in MS
Almost 10 years ago, Hulst and colleagues identified changes in the integrity of white matter, which were associated with cognitive impairment in individuals with MS . Over the last 2 years, several studies have attempted to clarify the contribution of structural and functional changes within the CNS that might underlie cognitive impairment in individuals with MS. A magnetic resonance imaging (MRI) study in 51 individuals with MS and cognitive impairment noted higher levels of white matter lesions and lower volumes of deep and cortical grey matter structures  when compared with brain scans from individuals with MS and no cognitive impairment. A second study by Dekker and colleagues  similarly reported grey matter atrophy in individuals with MS, noting that it occurred as an early event in MS pathology, whilst white matter lesions typically occurred as late events.
A multiparametric structural and functional MRI study  further examined the contribution of regional white matter lesions, abnormalities in white matter connectivity, grey matter atrophy and resting-state functional connectivity alterations to cognitive impairment in individuals with MS. Approximately one-third of the individuals with MS enrolled had cognitive impairment, which was noted to be associated with structural damage in strategic white and grey matter regions rather than resting-state functional connectivity alterations.
Is there a role for cognitive rehabilitation?
A review by DeLuca and colleagues published in 2020  notes an increased frequency in publications of studies examining the efficacy of cognitive rehabilitation in MS, with a few effective cognitive rehabilitation programmes for individuals with MS identified. Similarly, Chen and colleagues  stated that there is evidence that cognitive rehabilitation programs (either restorative or compensatory) are efficacious in treating MS-related cognitive dysfunction and that clinicians should consider this low-cost, low-risk, yet effective treatment approach for their patients. A recently published randomized trial  aimed to identify characteristics of individuals with MS that could be associated with response and non-response to cognitive training. Demographics, clinical variables and baseline cognition and structural MRI did not differ between responders and non-responders, however, non-responders exhibited a higher baseline functional connectivity between the default-mode network and the ventral attention network, compared with responders and healthy controls.
Promoting continued advances in research
ECTRIMS welcomes this increased knowledge around the factors underlying and influencing the development of cognitive impairment in individuals with MS and applauds the efforts of the scientific community to constantly improve our understanding of the pathogenesis of this aspect of MS. We remain optimistic that ongoing research will continue to improve our knowledge of how the quality of life of individuals with MS is impacted by their disease.
ECTRIMS Insights articles are produced with an intent of being a neutral source of information sharing and objective analysis for the MS and neuroscience community. Unless otherwise stated, cited information in our articles does equivocate official endorsement from ECTRIMS.
 Zhang J, et al. Front Neurol. 2021 Jul 8;12:671894.
 Yazgan YZ, et al. Clin Neurol Neurosurg. 2021 Jan;200:106398.
 Rimkus CM, et al. Mult Scler Relat Disord. 2018 May;22:41–48.
 Estrada-López M, et al. Neurol Int. 2021 Jul 22;13(3):335–342.
 Krause JS, et al. Arch Phys Med Rehabil. 2022 Jun 17:S0003-9993(22)00463-4.
 van Gorp DAM, et al. Neurol Sci. 2019 Dec;40(12):2555–2564.
 Hulst HE, et al. Neurology. 2013 Mar 12;80(11):1025–1032.
 Engl C, et al. J Neurol. 2020 Aug;267(8):2307–2318.
 Dekker I, et al. Neuroimage Clin. 2021;29:102550.
 Conti L, et al. Eur J Neurol. 2021 Nov;28(11):3749–3759.
 DeLuca J, et al. Nat Rev Neurol. 2020 Jun;16(6):319–332.
 Chen MH, et al. J Neurol. 2021 Dec;268(12):4908–4914.
 Prouskas SE, et al. Mult Scler. 2022