Predicting cognitive decline in multiple sclerosis: a 5-year follow-up study

Abstract

Cognitive decline is common in multiple sclerosis and strongly affects overall quality of life. Despite the identification of cross-sectional MRI correlates of cognitive impairment, predictors of future cognitive decline remain unclear. The objective of this study was to identify which MRI measures of structural damage, demographic and/or clinical measures at baseline best predict cognitive decline, during a 5-year follow-up period. A total of 234 patients with clinically definite multiple sclerosis and 60 healthy control subjects were examined twice, with a 5-year interval (mean = 4.9 years, standard deviation = 0.9). An extensive neuropsychological evaluation was performed at both time points and the reliable change index was computed to evaluate cognitive decline. Both whole-brain and regional MRI (3 T) measures were assessed at baseline, including white matter lesion volume, diffusion-based white matter integrity, cortical and deep grey matter volume. Logistic regression analyses were performed to determine which baseline measures best predicted cognitive decline in the entire sample as well as in early relapsing-remitting (symptom duration <10 years), late relapsing-remitting (symptom duration ≥10 years) and progressive phenotypes. At baseline, patients with multiple sclerosis had a mean disease duration of 14.8 (standard deviation = 8.4) years and 96/234 patients (41%) were classified as cognitively impaired. A total of 66/234 patients (28%) demonstrated cognitive decline during follow-up, with higher frequencies in progressive compared to relapsing-remitting patients: 18/33 secondary progressive patients (55%), 10/19 primary progressive patients (53%) and 38/182 relapsing-remitting patients (21%). A prediction model that included only whole-brain MRI measures (Nagelkerke R2 = 0.22, P < 0.001) showed cortical grey matter volume as the only significant MRI predictor of cognitive decline, while a prediction model that assessed regional MRI measures (Nagelkerke R2 = 0.35, P < 0.001) indicated integrity loss of the anterior thalamic radiation, lesions in the superior longitudinal fasciculus and temporal atrophy as significant MRI predictors for cognitive decline. Disease stage specific regressions showed that cognitive decline in early relapsing-remitting multiple sclerosis was predicted by white matter integrity damage, while cognitive decline in late relapsing-remitting and progressive multiple sclerosis was predicted by cortical atrophy. These results indicate that patients with more severe structural damage at baseline, and especially cortical atrophy, are more prone to suffer from cognitive decline. New studies now need to further elucidate the underlying mechanisms leading to cortical atrophy, evaluate the value of including cortical atrophy as a possible outcome marker in clinical trials as well as study its potential use in individual patient management.

Frontoparietal connectivity correlates with working memory performance in multiple sclerosis

“…In this study we assessed the cortical circuits that support verbal working memory in patients with relapsing-remitting multiple sclerosis with minimal or no burden of neurological disability (EDSS ≤ 3). These patients report a common clinical pattern of difficulties in the performance of daily cognitive tasks involving working memory, but without clear evidence in the clinical tests applied in their evaluation routines (Louapre et al, 2014;Schoonheim et al, 2015;Schoonhoven et al, 2018;Eijlers et al, 2018). Accordingly, we observed no significant differences in WM performance, but clear neurophysiological differences between patient and control groups.…”

Cognitive impairment as one of the important non‐motor symptoms in multiple sclerosis and neuromyelitis optica spectrum disorders

“…In the majority of those cases, long-term memory (responsible for learning and recalling abilities) and working memory are disturbed. 18 The patients with PPMS presented with a wider range of cognitive deficits in information processing speed, attention, working memory, executive function and verbal episodic memory. 9 However, independent assessment of attention is difficult, and this cognitive domain is strongly connected with other cognitive domains, such as information processing speed, working memory and fatigue.…”

“…This symptom was more pronounced in patients with progressive (primary-progressive MS [PPMS] and secondary progressive MS [SPMS]) MS than in patients with RRMS. 18 The patients with PPMS presented with a wider range of cognitive deficits in information processing speed, attention, working memory, executive function and verbal episodic memory. 15 A recent meta-analysis also showed differences in verbal learning and all measures of verbal memory between patients with PPMS and RRMS.…”

Longitudinal patterns of cortical thinning in multiple sclerosis

“…Increasing evidence from both cross‐sectional and longitudinal analyses points towards an association of cortical GM pathology such as cortical lesions and atrophy with physical and especially with cognitive dysfunction (Bergsland et al, ; Eijlers et al, ; Fisniku et al, ). However, the exact anatomical substrate of the cortical GM loss driving disease progression is still poorly understood.…”