The following is a summary of some of the key studies on cognitive dysfunction in multiple sclerosis presented at this year’s European Academy of Neurology virtual congress.

BICAMS long-term follow-up: The Brief International Cognitive Assessment for MS (BICAMS) comprises three tests: the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II) and Brief Visuospatial Memory Test (BVMT-R). An international effort was made to validate the use of BICAMS in clinical practice and individual countries have reported their findings. The Canadian cohort reported a rate of impairment in one or more cognitive tests of 57.9% of MS patients (Walker et al. J Neurol Sci 2016;362:147-152).

The Irish cohort reported that only 43% of MS patients scored within the normal range on all three tests compared to 83% of healthy controls (O’Connell et al. Mult Scler Relat Disord 2015;4:521-525). At the 5-year follow-up (mean age 49 years), cognitive function appeared to have stabilized: there was no change in SDMT and there were significant improvements in BVMT-R and CVLT (Gaughan et al. EAN 2020; abstract EPR1177). Subjects also demonstrated no change in anxiety scores and a significant improvement in depression scores at follow-up.

Cognitive impairment phenotypes: A large analysis of 1039 consecutive MS patients undergoing cognitive testing (Brief Repeatable Battery, Stroop Test) at six Italian MS centres reported that five cognitive phenotypes could be distinguished (De Meo et al. EAN 2020; abstract O3032). The phenotypes were Preserved Cognition (28%); Mild Executive/Memory Impairment with other domains preserved (13%); Mild Multi-domain Impairment with executive function preserved (36%); Severe Executive/Attention Impairment with mild cognitive impairment in other domains (19%); and Severe Executive/Information-processing Impairment with preserved memory and mildly impaired attention (3%). Patients with preserved cognition typically had a shorter disease duration and lower EDSS score, but this group did include some SPMS/PPMS patients with high EDSS scores. Conversely, severely impaired patients tended to have a longer disease duration and a progressive phenotype, but there were some with early MS. A further observation was that 47% of PPMS patients had a mild multi-domain phenotype.

Retirement/unemployment and cognitive decline: While cognitive impairment is associated with an increased risk of unemployment, the opposite also appears to hold, according to a 9-year study of an aging population (n=3153) in Russia (Titarenko et al. EAN 2020; abstract EPO3013). The study serially assessed immediate and delayed-recall memory, executive function (verbal fluency), and processing speed. A lower educational attainment was associated with a more rapid decline in memory function independent of age. Men who terminated employment (retired or not employed in the previous 12 months) had a steeper rate of decline in memory function compared to those remaining employed; this effect was independent of age and educational level.

Theory of mind deficits and cognitive impairment in MS: Theory of mind (ToM) is the ability to intuit beliefs, intentions and emotions to oneself or others and a number of studies have reported ToM deficits in MS patients (Raimo et al. Neuropsychology 2017;31:811-821. Batista et al. Arch Clin Neuropsychol 2018;33:541-551). While ToM deficits may suggest cognitive impairment, the two domains of functioning may differ in some respects. An Italian study administered the SDMT and the Reading the Mind in the Eyes Test (RMET) to score cognition and ToM, respectively, in 90 MS patients (mean age 44 years) (Pardini et al. EAN 2020; abstract EPR3077). There were significant differences between RRMS and progressive MS groups with respect to SDMT score and RMET score. Interestingly, while SDMT and RMET scores were correlated for the full sample, they were not correlated in progressive MS patients, suggesting that cognitive function and ToM may deteriorate somewhat differently in progressive MS. The authors suggested that RMET may be assessing a different cognitive construct not fully captured by SDMT. They recommended adding RMET to the battery of neuropsychological assessments to give a more complete picture of cognitive changes in MS patients.