To compare clinically stable and unstable people with Multiple Sclerosis (PwMS) on their longitudinal cognitive performance.

Recent papers call for longitudinal large-sample studies in Multiple Sclerosis (MS) cognitive research. There is a need for rigorous and comprehensive description of cognitive abilities of PwMS according to their level of disease progression and to examine the role of cognition as a disability progression marker.

Of the total 1237 PwMS after the first demyelinating event suggestive of MS or with clinically definitive MS from the GQ study, 1054 PwMS with all cognitive, MRI and clinical data available (from timepoints in months 0, 12 and 24) were included into the analysis (70% females, age m=38.3±9, Expanded Disability Status Scale (EDSS) Md=2, years of education Md=14). 4 groups of PwMS were described based on the criteria of clinical stability/instability (stability: no EDSS worsening, no new relapses over the 2-years follow-up) and stability/instability in BICAMS+PASAT cognitive tests (cognitive worsening confirmed in at least two tests in accordance with Classical Test Theory procedures).

Of the total 1054 PwMS, 795 (75.4%) were clinically and cognitively stable over the two-years follow-up. 123 (11.7%) PwMS worsened in cognitive performance but stayed clinically stable. 119 (11.3%) PwMS experienced disease progression with no cognitive decline and 17 (1.6%) worsened in both clinical and cognitive measures. Cognitively worsening PwMS showed longer disease duration, had more serious disease course status and higher EDSS scores [F(3, 1050) = 17.8, p < 0.00].

Classical disease progression markers and measures of cognitive performance seem to be largely mutually independent over the 2-years follow-up period, even though our data show clear connection between cognitive performance and MS disease course. Thus cognitive assessment can identify important group of PwMS who show significant worsening in cognitive measures but who would be missed by classical clinical assessment of the disease progression.