A newly-published set of recommendations advocates increased professional and patient awareness of MS-related cognitive symptoms and their management. The recommendations were endorsed by the U.S. National MS Society, the Consortium of Multiple Sclerosis Centers and the International MS Cognition Society (Kalb et al. Mult Scler 2018; epublished October 10, 2018). Use of the Symbol Digit Modalities Test (SDMT) or other validated test is advised early on when the patient is clinically stable, with re-assessments at least annually to detect new-onset cognitive impairment, detect disease activity and evaluate progression of cognitive impairment. Annual screening for depression is also recommended.

The authors noted that few pivotal trials of disease-modifying therapies have included cognitive outcome measures; interpretation of these data is hampered by the short duration of the studies and methodological issues. The largest study on cognition and DMT use was COGIMUS, which reported that the proportion of patients with cognitive impairment remained stable during treatment with beta-interferon-1a (18.0% at baseline, 22.6% in Year 5) (Patti et al. PLoS One 2013;8:e74111). More recently, a one-year study found that 28.5% of patients receiving first-line natalizumab showed clinically meaningful improvements in cognitive processing speed (Rorsman et al. Acta Neurol Scand 2018;137:117-124).

At ECTRIMS 2018, the StarTec study examined cognitive outcomes in a real-world setting in 167 patients treated with dimethyl fumarate (Zipoli et al. ECTRIMS 2018; abstract P457). Patients were assessed at baseline and every 12 months using Rao’s Brief Repeatable Battery (BRB), the Stroop test and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Cognitive impairment was defined as failure in >2 of 10 batteries (BRP and Stroop). Overall, 29% of patients had cognitive impairment at baseline; 55.9% experienced no further cognitive deterioration with DMF at two years. In the full cohort, 49.7% did not develop cognitive impairment during DMF, suggesting that treatment may delay the onset of cognitive dysfunction. A majority of patients were relapse-free (80.6%) and had no six-month disability progression (94.1%) during the two-year observation period. DMF was also associated with beneficial effects on fatigue, depression and quality of life.

The benefits of treatment on cognition may be due, in part, to effects on grey-matter pathology. A separate presentation at ECTRIMS compared the effect of DMF versus no treatment on MRI parameters (Zuco et al. ECTRIMS 2018; abstract P580). During the two-year prospective study, the number of new cortical lesions was significantly lower in the DMF-treated versus untreated group (0.2 vs. 2.9). The rate of brain atrophy at two years was normalized at 0.36% with DMF. Of particular interest was a more pronounced cortical thinning in several brain regions (hippocampus, cingulate, insula, superior frontal gyrus) in the untreated group. A number of studies have shown an association between cognitive impairment and grey-matter volume loss, notably to the thalamus and basal ganglia (Cruz-Gomez et al. Neuroreport 2018;29:547-552; Houtchens et al. Neurology 2007;69:1213-1223). The authors concluded that DMF appears to delay the progression of focal and diffuse CNS damage, with robust effects on both white-matter and grey-matter pathology.