Cognitive trajectories in relapsing-remitting multiple sclerosis: Evidence of multiple evolutionary trends.

BACKGROUND: Cognitive impairment (CI) frequently occurs in multiple sclerosis (MS) and is assumed to increase over time. However, recent studies have suggested that the evolution of cognitive status in patients with MS may be more heterogeneous than expected. Predicting CI remains also challenging, and longitudinal studies exploring the baseline determinants of cognitive performances are limited. No studies have explored the predictive value of patient-reported outcome measures (PROMs) regarding future CI. OBJECTIVE: To explore the evolutionary patterns of cognitive status in a cohort of RRMS patients initiating a new disease modifying treatment (DMT), and to determine whether PROMs may have a predictive value for future CI. METHODS: The present prospective study is a 12-month follow-up of a cohort of 59 RRMS patients who underwent yearly a comprehensive, multiparametric assessment combining clinical (with EDSS assessment), neuropsychological (BVMT-R, SDMT, CVLT-II), MRI-derived metrics and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A longitudinal logistic regression analysis was performed to find baseline correlates of CI at 12 months (T1). RESULTS: A total of 33 patients (56%) were defined as cognitively impaired at baseline, and 20 (38%) were defined as impaired at follow-up after 12 months. The mean raw scores and Z-scores of all the cognitive tests were significantly improved at T1 (p < 0.05). There was a statistically significant improvement in most PROM scores at T1 (p < 0.05) in comparison with baseline scores. Among the variables assessed, lower education and physical disability level at baseline correlated with impaired SDMT (OR: 1.68, p = 0.01; OR: 3.10, p = 0.02, respectively) and impaired BVMT-R (OR: 4.08, p=<0.001; OR: 4.82, p = 0.001, respectively) at T1. Neither baseline PROMs nor MRI volumetric parameters were predictive of cognitive performances at T1. CONCLUSIONS: These findings provide additional evidence that evolution of CI in MS may be a dynamic phenomenon and will not usually follow an inevitable, declining trajectory, and do not support the utility of PROMs in predicting CI in RRMS. The present study is still ongoing to determine whether our findings are confirmed at 2 and 3 years of follow-up.

Patient-reported outcome measurements in a selective cohort of relapsing-remitting multiple sclerosis patients: relationships with physical disability, cognitive impairment, and MRI-derived metrics.

BACKGROUND: The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. OBJECTIVE: To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. METHODS: In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. RESULTS: Of the 59 RRMS patients (mean age 39 ± 9.8 years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p < 0.05), except for the psychological component of MSIS-29, BDI and DEX-Q scores. No significant correlation was found between PROMs and cognitive performances. The cross-sectional logistic regression analysis included age, gender (female), education, EDSS, hippocampus and FLAIR lesion volumes as significant predictors of cognitive impairment. CONCLUSIONS: The data highlight that PROMs provide valuable information on the well-being of PwMS closely paralleling the extent of MS-related disability, as measured by the EDSS. Additional research should determine the relevance of PROMs as longitudinal outcome measures.