Cognitive Performance In Multiple Sclerosis Patients Research Articles

Antioxidant supplements and cognition in Multiple Sclerosis: a systematic review (P14-3.003)

<h3>Objective:</h3> We aimed to conduct a systematic review to examine whether there is an association between antioxidants supplements and cognitive performance in MS patients. <h3>Background:</h3> Cognitive dysfunction is a debilitating characteristic of multiple sclerosis (MS) that affects approximately 60% of patients. To date, the only effective treatments for cognitive decline are cognitive rehabilitation and exercise training. While previous studies reported the beneficial effect of antioxidants on MS patients, several other studies investigated the effect of antioxidant supplements on the cognitive performance of MS patients. <h3>Design/Methods:</h3> We searched PubMed, Embase, Scopus, and Web of Science for the identification of relevant studies in November 2021. We included control trials, cohort, case-control, and cross-sectional studies which showed the effect of any type of antioxidants on cognitive performance in MS patients. <h3>Results:</h3> After screening 12 papers were included in our study. Our review included three studies that examined the effect of ginkgo Biloba on cognitive performance, two examined the Mediterranean diet, and remained studies each investigated the vitamin A, Omega 5, Omega 3, estriol, epigallocatechin-3-gallate (EGCG), Boswellia papyrifera, and paleolithic diet. Overall, it seems that there were no benefits for antioxidant administration on cognitive performance in MS patients. <h3>Conclusions:</h3> It is complicated to draw a conclusion regarding the effect of an antioxidant-containing regimen and cognitive performance in MS patients. Findings from included studies failed to unequivocally support the beneficial effect of antioxidant consumption on cognitive performance in MS patients. <b>Disclosure:</b> Mr. Nabizadeh has nothing to disclose.

Antioxidant supplements and cognition in Multiple Sclerosis: a systematic review

Background: Cognitive dysfunction is a debilitating characteristic of multiple sclerosis (MS) that affects approximately 60% of patients. To date, the only effective treatments for cognitive decline are cognitive rehabilitation and exercise training. While previous studies reported the beneficial effect of antioxidants on MS patients, several other studies investigated the effect of antioxidant supplements on the cognitive performance of MS patients. We aimed to conduct a systematic review to examine whether there is an association between antioxidants supplements and cognitive performance in MS patients.Methods: We searched PubMed, Embase, Scopus, and Web of Science for the identification of relevant studies in November 2021. We included control trials, cohort, case-control, and cross-sectional studies which showed the effect of any type of antioxidants on cognitive performance in MS patients.Results: After screening 12 papers were included in our study. Our review included three studies that examined the effect of ginkgo Biloba on cognitive performance, two examined the Mediterranean diet, and remained studies each investigated the vitamin A, Omega 5, Omega 3, estriol, epigallocatechin-3-gallate (EGCG), Boswellia papyrifera, and paleolithic diet. Overall, it seems that there were no benefits of antioxidant administration on cognitive performance in MS patients.

The effectiveness of anodal tDCS and cognitive training on cognitive functions in multiple sclerosis; a randomized, double-blind, parallel-group study

BackgroundForty to 70% of patients with multiple sclerosis (MS) suffer from cognitive impairment during their illness. Only a few studies have examined the effects of anodal transcranial direct current stimulation (a-tDCS) along with cognitive training on cognitive performance in MS patients. This study aims to determine whether multi-session a-tDCS with or without cognitive training impacts cognitive performance in MS. MethodsEighty MS patients received a-tDCS, cognitive training, a-tDCS plus cognitive training, and sham for ten consecutive daily sessions. Cognitive function (including episodic memory, attention, and inhibitory control, working memory, and visuospatial skill) was measured at baseline, week 4, and week 12 after the intervention. ResultsAll cognitive functions significantly improved after the intervention compared to the sham condition. This effect also showed persistence during follow-up for some cognitive tasks in the a-tDCS and a-tDCS combined cognitive training groups. Although the cognitive training group experienced an immediate improvement in attention and inhibitory control, the difference was not significant at follow-up. Also, there were no significant differences between these three groups in cognitive scores after the intervention. Conclusiona-tDCS alone and a-tDCS paired with or without cognitive training as compared to sham appears to be a promising therapeutic option for cognitive performance in MS patients.

Targeted cognitive game training enhances cognitive performance in multiple sclerosis patients treated with interferon beta 1-a

BackgroundPrevention of cognitive decline in Multiple Sclerosis (MS) is of major importance. We explored the effect of a 6 months computerized game training program on cognitive performance in MS patients with mild cognitive impairment.MethodsThis was a single-center, randomized prospective study. We enrolled in this study 100 eligible MS patients treated with Interferon-beta-1a (Rebif). All had mild cognitive impairment in either executive function or information processing speed. Patients were randomized 1:1 to either use the cognitive games platform by HappyNeuron (HN) or receive no intervention. Executive function and information processing speed scores were measured at 3 and 6 months from baseline to evaluate the effect of game training on cognitive scores.ResultsIn both executive function and information processing speed, the game Training group showed significant improvement after 3 and 6 months. The Non-Training group showed mild deterioration in both domains at 3 months, and further deterioration that became significant at 6 months in executive function. Furthermore, at 6 months, the percent of patients in the Training group that improved or remained stable in both cognitive domains was significantly higher compared to the Non-Training group.ConclusionsOur findings suggest that cognitive game training has a beneficial effect on cognitive performance in MS patients suffering from mild cognitive impairment. While further evaluation is required to assess the longevity of that effect, we nonetheless recommend to MS patients to be engaged in cognitive gaming practice as part of a holistic approach to treating their condition.

A CSF biomarker of intrathecal B cells activation correlates with memory impairment in multiple sclerosis

Cognitive impairment (CI) is a common clinical feature of multiple sclerosis (MS), but its pathophysiology is only partially known. Cerebrospinal fluid (CSF) biomarkers, by reflecting the ongoing pathology, may help in better understanding the determinants of CI in MS. Kappa free light chain index (k-index) is a sensitive biomarker of intrathecal B cells activation. Herein, we investigated the association between k-index and cognitive performance in MS patients.

Optical Coherence Tomography Is Associated With Cognitive Impairment in Multiple Sclerosis.

Optical coherence tomography (OCT) is a sensitive method for quantifying retinal neuronal and axonal structures. Reductions in retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thicknesses have a reported association with white and grey matter atrophy in multiple sclerosis (MS). We hypothesized that the thinning of intraretinal layer measurements associates with cognitive decline in MS patients with no prior event of optic neuritis (ON). OCT and NeuroTrax computerized cognitive assessments were performed in 204 relapsing remitting MS patients with no history of ON or other conditions affecting the eye. Data were collected between 2010 and 2020 and retrospectively analyzed. Correlations were examined between cognitive performance and a lower RNFL or GCIPL thickness. A multilinear regression model was generated to assess the significance of these correlations regarding the disability score and disease duration. The 204 study participants had a mean age of 40.52 ± 11.8 years (mean ± SD) and disease duration of 9.80 ± 9.40 years. The mean RNFL thickness in this whole cohort was 82.22 ± 10.85 μm and the global cognitive score was 95.32 ± 12.32. The mean GCIPL thickness measured in a subgroup of 104 patients was 74.27 ± 10.37 μm. The RNFL and GCIPL both correlated with the global cognitive score (r = 0.174, P = 0.013 and r = 0.29, P = 0.03, respectively), and with various cognitive domains. However, the GCIPL showed stronger correlations than RNFL, particularly with executive function (r = 0.29, P = 0.003), attention (r = 0.332, P = 0.001), and the information processing speed (r = 0.25, P = 0.012). These correlations remained significant after correcting for confounders. OCT measurements correlate with cognitive performance in MS patients. OCT can thus be used to evaluate central nervous system neurodegeneration in MS, as reflected by cognitive decline.

The role of cognitive reserve in multiple sclerosis: A cross-sectional study in 526 patients

BackgroundCognitive impairment (CI) affects about 40–70% of multiple sclerosis (MS) patients. Brain MRI explains about 33–50% of the CI variance in MS. The cognitive reserve (CR) hypothesis has been postulated to identify other factors that can account for more variance in this outcome. The objective of this study was to explore the impact of CR on cognitive performance in MS patients. MethodsA total of 526 MS outpatients were recruited (70.9% females, 41.7 ± 11.1 years old). CR was cross-sectionally assessed by the CR Index questionnaire (CRIq). Cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tool to evaluate information processing speed, verbal memory and visuospatial memory. The role of CRIq in MS cognition was investigated by using multiple linear regression models to account for possible confounders. ResultsIn total 202 (38.4%) patients were found with CI (i.e. failure in at least one of the three cognitive tests used based on normative data from 212 healthy controls). The CRIq score of CI patients was lower than that of non-CI patients (p < 0.001). CRIq score was significantly correlated with information processing speed (rho = 0.364, p < 0.001), verbal memory (rho = 0.237, p < 0.001) and visuospatial memory (rho = 0.331, p < 0.001), having adjusted for age and sex. CRIq was also significantly associated with disability (rho = -0.188, p < 0.001) and depressive symptoms (rho = -0.220, p < 0.001). Roughly, CRIq, disability and depressive symptoms significantly explained 12.2–23.7% of cognitive performance in MS. A significant interaction between CRIq and disability was also found for information processing speed. ConclusionCR has a protective role in MS-related cognitive dysfunction. The differential effect of CR on distinct cognitive domains is supported. Interventions targeting CR to prevent cognitive impairment in MS patients are warranted by the study findings.

Cognitive function in multiple sclerosis: A long-term look on the bright side

Multiple sclerosis (MS) may lead to cognitive decline over-time. Characterize cognitive performance in MS patients with long disease duration treated with disease modifying drugs (DMD) in relation to disability and determine the prevalence of cognitive resilience. Cognitive and functional outcomes were assessed in 1010 DMD-treated MS patients at least 10 years from onset. Cognitive performance was categorized as high, moderate or low, and neurological disability was classified according to the Expanded Disability Status Scale (EDSS) as mild, moderate or severe. Relationship between cognitive performance and disability was examined. After a mean disease duration of 19.6 (SD = 7.7) years, low cognitive performance was observed in 23.7% (N = 239), moderate performance in 42.7% (N = 431), and 33.7% (N = 340) had high cognitive performance, meeting the definition of cognitively resilient patients. Within the group of patients with low cognitive performance, severe disability was observed in 50.6% (121/239), while in the group of patients with high cognitive performance, mild disability was observed in 64.4% (219/340). Differences between the group of patients with high cognitive performance and severe disability (4.5%) and the group of patients with low cognitive performance and mild disability (5.0%) were not accounted for by DMD treatment duration. The majority of DMD treated MS patients did not have cognitive decline that could impair their quality of life after disease of extended duration.

A simple measure of cognitive reserve is relevant for cognitive performance in MS patients.

Cognitive reserve (CR) contributes to preserve cognition despite brain damage. This theory has been applied to multiple sclerosis (MS) to explain the partial relationship between cognition and MRI markers of brain pathology. Our aim was to determine the relationship between two measures of CR and cognition in MS. One hundred and forty-seven MS patients were enrolled. Cognition was assessed using the Rao's Brief Repeatable Battery and the Stroop Test. CR was measured as the vocabulary subtest of the WAIS-R score (VOC) and the number of years of formal education (EDU). Regression analysis included raw score data on each neuropsychological (NP) test as dependent variables and demographic/clinical parameters, VOC, and EDU as independent predictors. A binary logistic regression analysis including clinical/CR parameters as covariates and absence/presence of cognitive deficits as dependent variables was performed too. VOC, but not EDU, was strongly correlated with performances at all ten NP tests. EDU was correlated with executive performances. The binary logistic regression showed that only the Expanded Disability Status Scale (EDSS) and VOC were independently correlated with the presence/absence of CD. The lower the VOC and/or the higher the EDSS, the higher the frequency of CD. In conclusion, our study supports the relevance of CR in subtending cognitive performances and the presence of CD in MS patients.

Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis

Objective: To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Methods: Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Results: Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Conclusion: Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior–inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

Subclinical MRI disease activity influences cognitive performance in MS patients

BackgroundThe pathological mechanisms underlying cognitive dysfunction in multiple sclerosis (MS) are not yet fully understood and, in addition to demyelinating lesions and gray-matter atrophy, subclinical disease activity may play a role. ObjectiveTo evaluate the contribution of asymptomatic gadolinium-enhancing lesions to cognitive dysfunction along with gray-matter damage and callosal atrophy in relapsing-remitting MS (RRMS) patients. MethodsForty-two treated RRMS and 30 controls were evaluated. MRI (3T) variables of interest were brain white-matter and cortical lesion load, cortical and deep gray-matter volumes, corpus callosum volume and presence of gadolinium-enhancing lesions. Outcome variables included EDSS, MS Functional Composite (MSFC) subtests and the Brief Repeatable Battery of Neuropsychological tests. Cognitive dysfunction was classified as deficits in two or more cognitive subtests. Multivariate regression analyses assessed the contribution of MRI metrics to outcomes. ResultsPatients with cognitive impairment (45.2%) had more cortical lesions and lower gray-matter and callosal volumes. Patients with subclinical MRI activity (15%) had worse cognitive performance. Clinical disability on MSFC was mainly associated with putaminal atrophy. The main independent predictors for cognitive deficits were high burden of cortical lesions and number of gadolinium-enhancing lesions. ConclusionsCognitive dysfunction was especially related to high burden of cortical lesions and subclinical disease activity. Cognitive studies in MS should look over subclinical disease activity as a potential contributor to cognitive impairment.

Impact of depression, fatigue, and global measure of cortical volume on cognitive impairment in multiple sclerosis.

Objective. To investigate the influence of demographic and clinical variables, such as depression, fatigue, and quantitative MRI marker on cognitive performances in a sample of patients affected by multiple sclerosis (MS). Methods. 60 MS patients (52 relapsing remitting and 8 primary progressive) underwent neuropsychological assessments using Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Beck Depression Inventory-second edition (BDI-II), and the Fatigue Severity Scale (FSS). We performed magnetic resonance imaging to all subjects using a 3 T scanner and obtained tissue-specific volumes (normalized brain volume and cortical brain volume). We used Student's t-test to compare depressed and nondepressed MS patients. Finally, we performed a multivariate regression analysis in order to assess possible predictors of patients' cognitive outcome among demographic and clinical variables. Results. 27.12% of the sample (16/59) was cognitively impaired, especially in tasks requiring attention and information processing speed. From between group comparison, we find that depressed patients had worse performances on BRB-N score, greater disability and disease duration, and brain volume decrease. According to multiple regression analysis, the BDI-II score was a significant predictor for most of the neuropsychological tests. Conclusions. Our findings suggest that the presence of depressive symptoms is an important determinant of cognitive performance in MS patients.

A Cohort Study of Cognitive Impairment in Patients of Multiple Sclerosis

Abstract Introduction:Multiple sclerosis (MS) is an inflammatory disease which disrupts the ability of nervous system to communicate, resulting in a wide range of signs and symptoms including physical, cognitive and psychiatric. Cognitive dysfunction is increasingly recognized as a critical factor in the quality of life of patients with MS. Remission of cognitive symptoms is uncommon, and cognitive decline may indicate progressive disease despite stable physical symptoms. Methods: A total of 30 patients of MS diagnosed by modified Mc Donald criterion 2010 had undergone MACFINS battery of Cognitive testing twice, first at the time of initial recruitement and then after a period of 6 months. Results: No significant cognitive decline was observed in patients after a mean follow up of 11 months. There was mild but not significant impairment in EDSS. There appears a strong direct correlation between all neuropsychological tests and physical disability. Most significant correlation of EDSS is seen with PASAT (P=0.002), BVMT1(P= 0.008), BVMT2(P=0.007), COWAT(P=0.0002) and Stroop B(P=0.009). Conclusion: Cognitive deterioration occurs probably insidiously and inconsistently in patients with MS. EDSS has significant direct correlation with cognitive impairment in these patients. A larger sample size study is required to conclusively establish cognitive performance in MS patients.

Altered functional connectivity and performance variability in relapsing–remitting multiple sclerosis

Background: Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients. Objectives: This study investigated alterations in resting-state functional connectivity associated with within-person performance variability in MS patients. Methods: Relapsing–remitting MS patients and matched healthy controls completed structural MRI and resting-state fMRI (rsfMRI) scans, as well as tests of information processing speed. Performance variability was calculated from reaction time tests of processing speed. rsfMRI connectivity was investigated within regions associated with the default mode network (DMN). Relations between performance variability and functional connectivity in the DMN within MS patients were evaluated. Results: MS patients demonstrated greater reaction time performance variability compared to healthy controls (p<0.05). For MS patients, more stable performance on a complex processing speed task was associated with greater resting-state connectivity between the ventral medial prefrontal cortex and the frontal pole. Conclusions: Among MS patients, greater functional connectivity between medial prefrontal and frontal pole regions appears to facilitate performance stability on complex speed-dependent information processing tasks.

No Effect of Cooling on Cognitive Fatigue, Vigilance and Autonomic Functioning in Multiple Sclerosis

Background: Fatigue is a common symptom in Multiple Sclerosis (MS) and body cooling may be an important non-pharmacological treatment strategy for fatigue by, for instance, reducing the loss of axonal conduction efficiency due to Uhthoff’s phenomenon. However, up to now, no studies have demonstrated such a treatment effect for mentally induced fatigue. Methods: In this single-blinded randomized placebo controlled cross-over design we studied the effects of cooling on cognitive fatigue and autonomic functioning (heart rate variability and sympathovagal balance measures) during a vigilance task in 31 MS patients and 10 controls. Results: Task performance, fatigue and sympathovagal balance did not differ between verum- and placebo condition after controlling for depressive mood. MS patients showed more omissions on the vigilance test than controls; their performance declined during the task and this correlated significantly with cognitive fatigue. Cardiac sympathetic drive remained unchanged during vigilance testing in MS patients, but it increased significantly in controls. Conclusion: Cooling has no impact on experienced cognitive fatigue and on cognitive performance in MS patients. Vigilance testing seems to be an appropriate behavioural measure of cognitive fatigue. Cardiac sympathetic drive to compensate for mental strain is reduced in MS patients, indicating an autonomic dysfunction.

Fatigue-related diurnal variations of cognitive performance in multiple sclerosis and stroke patients

Objective Cognitive impairment is a common symptom of multiple sclerosis (MS). The present study aimed to assess fatigue-related diurnal variations of cognitive performance in MS patients. Method Subjective cognitive fatigue and cognitive performance in three reaction time tasks differing in cognitive demands (alertness, Go/NoGo, divided attention) was measured at three different times of day on two consecutive days for MS patients, stroke patients, and healthy control participants. Results Objective measures of cognitive performance revealed poorer performance for both groups of patients than for controls. A diurnal decline of cognitive performance was only observed for the two groups of patients but not for healthy controls. This decline corresponded to the patients' subjective reports of increasing cognitive fatigue during the day. Conclusion Cognitive fatigue in both MS and stroke patients is not only reflected in subjective ratings but also affects objectively measured performance in cognitive tasks.

Neuropsychological testing and event-related potentials in the assessment of cognitive performance in the patients with multiple sclerosis—A pilot study

Aims The aim of the study was to evaluate cognitive impairment in multiple sclerosis (MS) patients using neuropsychological testing (NT) and auditory event-related potentials (ERPs) with reference to clinical variables, with an attempt to re-assess NT and ERP results after a year. Methods The study comprised 21 patients with MS. ERPs results were compared to age-matched controls. Correlations were searched among ERPs and NT results, duration of MS and disability. NT and ERPs were repeated after a year and their results were compared with the initial ones. Results In NT, 90–100% of patients showed impaired memory and attention. Latencies of ERPs were prolonged in patients compared with controls. NT results correlated with clinical variables and N2 parameters. Results of NT, but not ERPs, improved after a year. Conclusions MS patients present with moderate cognitive impairment and ERP abnormalities, with dysfunction of subcortical–prefrontal circuit as their possible background. NT are more useful than ERP in monitoring cognitive performance in MS patients.