Patterns of cognitive decline across different multiple sclerosis clinical courses

Abstract

Background: It is still unclear whether patients with progressive MS (PMS) present a distinct pattern of cognitive impairment (CI) and different trajectories of cognitive and clinical decline compared to patients with relapsing-remitting MS (RRMS) with similar age. In addition, the role of reserve (cognitive and cerebral) in cognitive decline in the different forms of MS is not fully understood, and some studies suggest that its effects reduce in the progressive forms.

Objective: To assess the trajectories of cognitive decline in RRMS and PMS patients with similar age, also evaluating the predictive power of baseline clinical and MRI features on cognitive outcomes at follow-up.

Methods: Fifty-four patients were enrolled (30 PMS, 24 RRMS) and underwent brain MRI (3T - FreeSurfer and Spinal Cord Toolbox), clinical examination (Expanded Disability Status Scale - EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT) and neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests - BRBN, Tower of London (TOL) test and Boston Naming Test at baseline (time 1) and after 4 years (time 2). We also evaluated cognitive and brain reserve. We defined CI as the presence of impairment in >1 domain.

Results: At baseline (time 1), 37.2 % of the individuals presented CI and 52.4 % at time 2, which was more frequent in the PMS group. There was also a higher frequency of impairment in the visual memory and Information Processing Speed (IPS) cognitive domains in the PMS group in both study times. However, there were no major statistical differences between RMS/PMS groups in the evolution of clinical, cognitive and neuroimaging variables after 4 years of follow-up, except for a worse verbal memory decline (p = 0.040) and corpus callosum atrophy (p = 0.014) in PMS group. For EDSS worsening, the best predictive factor was the spinal cord area (β = -0.428), and for T25FW, the striatum volume (β = -0.467). For cognitive deterioration, striatum volume and cortical thickness were the best predictors. We found a protective effect of cognitive reserve on the decline of the domains of planning (β = 0.601) and IPS (β = 0.482) for the overall sample and the PMS group (β = 0.498 and β = 0.468, respectively).

Conclusions: We found cognitive deterioration after four years of follow-up in RRMS and PMS groups. Nevertheless, there were no major differences between these groups (with similar age, education and disease duration) in the trajectories of clinical, cognitive and neuroimaging variables during this 4-year period. We observed a protective effect of cognitive reserve in the overall sample and the PMS group.

Keywords: Cognitive dysfunction; Disease progression; Magnetic resonance imaging; Multiple sclerosis; Prognosis.