The relationships between cognitive impairment that exist during the clinical course of multiple sclerosis (MS) remain poorly described. The effect of disease duration has been studied in a few ...longitudinal cohorts and some cross-sectional studies that suggest that cognitive deficits tend to extend with disease duration. However, the effect of disease duration seems to be confounded by the effect of age. At the pre-clinical stage, cognitive deficits have been observed in patients with radiologically isolated syndromes, and their profile is similar than in clinically isolated syndromes (CIS) and relapsing-remitting MS (RRMS). The frequency of cognitive impairment tends to be higher in RRMS than in CIS. In these phenotypes, slowness of information processing speed (IPS) and episodic verbal and visuo-spatial memory deficits are frequently observed, but executive functions, and in particular verbal fluency, could also be impaired. More frequent and severe deficits are reported in SPMS than in RRMS with more severe deficits for memory tests, working memory and IPS. Similarly to what is observed in SPMS, patients with primary progressive MS (PPMS) present with a wide range of cognitive deficits in IPS, attention, working memory, executive functions, and verbal episodic memory with more tests and domains impaired than RRMS patients. Altogether these data suggested that not only the duration of the disease and age play an important role in the cognitive profile of patients, but also the phenotype itself, probably because of its specific pathological mechanism.
•The minimal cognitive assessment in multiple sclerosis should include neuropsychological (NP) tests assessing information processing speed and episodic memory.•Besides classical NP tests, ecological ...tools are increasing in number for detecting disabling cognitive deficits in everyday-like conditions.•Cognitive impairment has negative impact on social and vocational activities in persons living with MS.
Cognitive impairment (CI) is frequent in patients with multiple sclerosis (PwMS) and could negatively affect family social and vocational activities. Detecting CI is clinically relevant, so the emerging question is the strategy for assessing cognition in MS.
An update on cognitive assessment in PwMS with use of standard neuropsychological (NP) tests and ecological tools.
The minimal cognitive assessment in MS should include at least NP tests assessing information processing speed (IPS) and verbal and visuospatial episodic memory. The IPS could be easily and quickly evaluated with symbol digit substitution tests by using paper for the oral version of the Symbol Digit Modalities Test or a laptop for the Computerised Speed Cognitive Test. The comprehensive NP battery must be performed by a qualified neuropsychologist to adequately characterize the extent and severity of CI in PwMS. The quiet and controlled environment used for this standardized assessment could be a limitation for generalizing the results because it does not reflect real daily life conditions. Thus, this context could decrease the ability to detect some cognitive deficits that could occur only in more complex situations. Thus, ecological evaluation seems a complementary and promising approach for detecting cognitive abnormalities in daily activities.
Recent efforts have been made to detect and characterize cognitive deficits in PwMS. Some IPS and episodic memory NP tests have been validated in MS and should be proposed to patients in the clinical setting. Besides NP tests, ecological tools are becoming important for detecting cognitive dysfunction in everyday-like conditions. Further research is needed to validate relevant tools for monitoring cognition in MS and the ability to detect clinically meaningful change in longitudinal studies.
To characterize the cognitive abilities of patients with primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) compared with healthy controls (HCs) matched ...for age, sex, and education level while considering the different characteristics of PPMS and RRMS and to compare the cognitive patterns of these types of multiple sclerosis.
Forty-one patients with PPMS, 60 patients with RRMS, and 415 HCs were recruited in a cross-sectional study. Controls were divided into 20 groups according to age, sex, and education level. Participants were assessed with a large battery of neuropsychological (NP) tests that included a modified version of the Brief Repeatable Battery, the Stroop test, computerized tests from the Test of Attentional Performance battery, the numerical span test, and the Rey Complex Figure.
Patients with PPMS performed worse than their matched HCs on nearly all NP tests. Patients with RRMS performed worse than matched HCs on a computerized digit-symbol substitution task and the alertness test, reaction time for visual scanning, and Paced-Auditory Serial Addition Test-3 seconds. Patients with PPMS had worse NP scores and were more impaired in cognitive domains than patients with RRMS. After controlling for Expanded Disability Status Scale score, the results remained unchanged.
The patients with PPMS presented with a wide range of cognitive deficits in information processing speed, attention, working memory, executive function, and verbal episodic memory, whereas the impairments in patients with RRMS were limited to information processing speed and working memory compared with their matched HCs. Cognitive deficits were more severe in patients with PPMS than in patients with RRMS.
Structural and functional connectivity abnormalities have been reported previously in multiple sclerosis. However, little is known about how each modality evolution relates to the other. Recent ...studies in other neurological disorders have suggested that structural-functional coupling may be more sensitive in detecting brain alterations than any single modality. Accordingly, this study aimed to investigate the longitudinal evolution of structural-functional coupling, both at the global and modular levels, in the first year following clinically isolated syndrome. We hypothesized that during the course of multiple sclerosis, patients exhibit a decoupling between functional and structural connectivity due to the disruptive nature of the disease. Forty-one consecutive patients with clinically isolated syndrome were prospectively enrolled in this study, along with 19 age-, sex- and educational level-matched healthy control subjects. These participants were followed for 1 year and underwent resting-state functional MRI and diffusion tensor imaging at each time point, along with an extensive neuropsychological assessment. Graph theory analysis revealed structural reorganization at baseline that appeared as an increase in the clustering coefficient in patients compared to controls (P < 0.05), as well as modular-specific alterations. After 1 year of follow-up, both structural and functional reorganization was depicted with abnormal modular-specific connectivity and an increase of the functional betweenness centrality in patients compared to controls (P < 0.01). More importantly, structural-functional decoupling was observed in the salience, visual and somatomotor networks. These alterations were present along with preserved cognitive performance at this stage. These results depict structural damage preceding functional reorganization at a global and modular level during the first year following clinically isolated syndrome along with normal cognitive performance, suggesting a compensation mechanism at this stage of the disease. Principally, structural-functional decoupling observed for the first time in multiple sclerosis suggests that functional reorganization occurs along indirect anatomical pathways.
Background:
The relationship between structural and functional deficits in multiple sclerosis (MS) is unclear.
Objective:
This study explored structure-function relationships during the 5 years ...following a clinically isolated syndrome and their role in cognitive performance.
Methods:
Thirty-two patients were enrolled after their first neurological episode suggestive of MS and followed for 5 years, along with 10 matched healthy controls. We assessed structural (using diffusion tensor imaging) and functional (using resting-state functional magnetic resonance imaging (fMRI)) brain network metrics, clinical and cognitive scores at each follow-up visit. Structural–functional coupling, calculated as the correlation coefficient between strengths of structural and functional networks, was used to assess structure–function relationships.
Results:
Structural clustering coefficient was significantly increased after 5 years, whereas characteristic path length decreased. Structural connections decreased after 1 year and increased after 5 years. Functional connections and related path lengths were decreased after 5 years. Structural–functional coupling had increased significantly after 5 years. This structural–functional coupling was associated with cognitive and clinical evolution, with stronger coupling associated with a decline in both domains.
Conclusion:
Our findings provide novel biological evidence that MS leads to a more constrained anatomical-dependant functional connectivity. The collapse of this network seems to lead to both cognitive worsening and clinical disability.
The association between cognitive impairment, health-related quality of life (HRQoL) and vocational status has been studied in recent years in cross-sectional studies in multiple sclerosis (MS), but ...longitudinal data are still lacking. This study assesses this association in a sample of 65 newly diagnosed MS patients followed longitudinally. Each patient underwent a standardised clinical assessment, cognitive tests and the HRQoL SEP-59 questionnaire six months after the MS diagnosis (baseline) and seven years later (y7).Vocational status was also established at baseline and at y7 in MS patients. The HRQoL at baseline was severely reduced in MS patients compared with healthy subjects. The independent predictors for HRQoL composite scores at y7 were the baseline depression score and the memory
Z
-score. Accordingly, 81.5 % of MS patients worked at baseline and only 54.4 % worked at y7. Among the MS patients who did not work at y7, 72.7 % of them were cognitively impaired, while 27.3 % were unimpaired at baseline. The vocational status at y7 was significantly associated with the baseline IPS
Z
-score, EDSS and age. Vocational status at y7 and its change over 7 years was significantly associated with cognitive deterioration. IPS or memory dysfunction in the early stages of MS is correlated with a decreased level in health perception, independent of fatigue, depression and physical disability. Cognitive impairment at the diagnosis of MS increases the risk of changing vocational status in MS patients seven years later.
Background:
The Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) is a short neuropsychological battery for persons with multiple sclerosis (PwMS).
Objectives:
The main objective ...of the study is to validate the BCCAMS.
Methods:
PwMS and healthy subjects (HS) were evaluated using the BCCAMS which include two computerized tests, the Computerized Speed Cognitive Test and the Computerized Episodic Visual Memory Test (CEVMT), a newly developed visuospatial memory test, and the French learning test. The Minimal Assessment of Cognitive Function in MS (MACFIMS), including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tests, was also administered. Regression-based norms of the BCCAMS were calculated in 276 HS. BCCAMS was compared with BICAMS and MACFIMS for detection of cognitive impairment (CI).
Results:
Out of 120 PwMS, CI was detected using the BCCAMS, BICAMS (one impaired test), and MACFIMS (two impaired tests) in 59.1%, 50%, and 37.9%, respectively. The BCCAMS produced the same predictive value as that of the BICAMS battery for detecting CI in the MACFIMS.
Conclusion:
This study validated the BCCAMS as a validated computerized short assessment for information processing speed and learning in MS.
Objectives:
Investigating differential vulnerability of thalamic nuclei in multiple sclerosis (MS).
Methods:
In a secondary analysis of prospectively collected datasets, we pooled 136 patients with ...MS or clinically isolated syndrome and 71 healthy controls all scanned with conventional 3D-T1 and white-matter-nulled magnetization-prepared rapid gradient echo (WMn-MPRAGE) and tested for cognitive performance. T1-based thalamic segmentation was compared with the reference WMn-MPRAGE method. Volumes of thalamic nuclei were compared according to clinical phenotypes and cognitive profile.
Results:
T1- and WMn-MPRAGE provided comparable segmentations (0.84 ± 0.13 < volume-similarity-index < 0.95 ± 0.03). Medial and posterior thalamic groups were significantly more affected than anterior and lateral groups. Cognitive impairment related to volume loss of the anterior group.
Conclusion:
Thalamic nuclei closest to the third ventricle are more affected, with cognitive consequences.
Background:
Cognitive impairment occurs in the earliest stages of multiple sclerosis (MS) together with altered functional connectivity (FC).
Objective:
The aim of this study was to investigate the ...evolution of dynamic FC states in early MS and their role in shaping cognitive decline.
Methods:
Overall, 32 patients were enrolled after their first neurological episode suggestive of MS and underwent cognitive evaluation and resting-state functional MRI (fMRI) over 5 years. In addition, 28 healthy controls were included at baseline.
Results:
Cognitive performance was stable during the first year and declined after 5 years.
At baseline, the number of transitions between states was lower in MS compared to controls (p = 0.01). Over time, frequency of high FC states decreased in patients (p = 0.047) and increased in state with low FC (p = 0.035). Cognitive performance at Year 5 was best predicted by the mean connectivity of high FC state at Year 1.
Conclusion:
Patients with early MS showed reduced functional network dynamics at baseline. Longitudinal changes showed longer time spent in a state of low FC but less time spent and more connectivity disturbance in more integrative states with high within- and between-network FC. Disturbed FC within this more integrative state was predictive of future cognitive decline.
Cognition is frequently impaired in the early stages of multiple sclerosis (MS). The predictive value of cognitive impairment on disability is unknown. The objective of this study was to correlate ...cognitive impairment and the progression of disability over 7 years. Forty-five patients, recruited after MS diagnosis, were followed for 7 years by yearly Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) evaluations and were classified as cognitively impaired (CI) or unimpaired (CU) according to neuropsychological testing at baseline. At baseline, 47.8% of patients were CI, with deficits in mainly memory and information processing speed (IPS). The baseline EDSS correlated significantly with one IPS test. The EDSS, but not the MSFC, deteriorated significantly over the 7 years in the whole group and the CI group, but not the CU group. A multivariate analysis showed correlations between the EDSS change over 5 and 7 years and two baseline tests evaluating IPS and verbal memory. The deterioration of the EDSS after 7 years was significantly correlated with verbal memory testing at baseline after adjustment for age and baseline EDSS. In conclusion, in this sample of MS patients early in the disease, the baseline IPS and verbal memory impairments predict the EDSS score 5 and 7 years later.
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