Cognitive Impairment In Multiple Sclerosis Research Articles

Teriflunomide, cognition and MRI: A longitudinal study

BackgroundAs cognitive impairment in multiple sclerosis (MS) is a frequent and disabling symptom, it is particularly important to identify treatments that have proven efficacy in this aspect of the disease. Several disease-modifying therapies for MS have been evaluated and shown to have a potential effect on cognition and its neurobiological correlates, but to date there is very little data on Teriflunomide (TRF). The aim of this study is to explore the influence of TRF on comprehensive cognitive function and its MRI correlations (global and focal brain volume) in relapsing-remitting multiple sclerosis (RRMS) after two years of therapy. MethodsTwenty-four patients with RRMS were evaluated at baseline and after two years of treatment with BCcogSEP, a French translation of the Brief Repeatable Battery (BRB-N) including 3 additional tests. We explored the performance evolution for each test and correlation with MRI data for all patients. We also differentiated MS patients with and without cognitive impairment. ResultsAfter two years of treatment, an improvement is observed at the Selective Reminding Test for mean number of words (p = 0.044), learning (p = 0.018), and delayed recall (p = 0.002) and at GoNoGo task (p = 0.022). At MRI, the corpus callosum volume variation correlates positively with SRT total recall test (p = 0,047). Intergoup analysis shows that the evolution of group performance differs only for the SRT total recall test. The comparison of patients with or without cognitive impairment showed a clear difference in white matter substance volume (p = 0,003) and in the Percentage Brain Volume Change (p = 0,016). ConclusionResults suggest that TRF treatment in RRMS has a positive effect in cognitive function, and specifically on long term verbal memory and inhibition. Neuroimaging data suggest a link between cognition and global and focal white matter volume, particularly in the corpus callosum which is involved in anatomical disconnection syndrome and therefore brain plasticity capacities.

Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = −0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.

Cognitive impairment in multiple sclerosis: from phenomenology to neurobiological mechanisms.

Multiple sclerosis (MS) is an autoimmune-mediated disease of the central nervous system characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of clinical symptoms, cognitive impairment (CI) is a common and disabling feature greatly affecting the patients' quality of life. Its prevalence is 20% up to 88% with a wide variety depending on the phenotype of MS, with highest frequency and severity in primary progressive MS. Involving different cognitive domains, CI is often associated with depression and other neuropsychiatric symptoms, but usually not correlated with motor and other deficits, suggesting different pathophysiological mechanisms. While no specific neuropathological data for CI in MS are available, modern research has provided evidence that it arises from the disease-specific brain alterations. Multimodal neuroimaging, besides structural changes of cortical and deep subcortical gray and white matter, exhibited dysfunction of fronto-parietal, thalamo-hippocampal, default mode and cognition-related networks, disruption of inter-network connections and involvement of the γ-aminobutyric acid (GABA) system. This provided a conceptual framework to explain how aberrant pathophysiological processes, including oxidative stress, mitochondrial dysfunction, autoimmune reactions and disruption of essential signaling pathways predict/cause specific disorders of cognition. CI in MS is related to multi-regional patterns of cerebral disturbances, although its complex pathogenic mechanisms await further elucidation. This article, based on systematic analysis of PubMed, Google Scholar and Cochrane Library, reviews current epidemiological, clinical, neuroimaging and pathogenetic evidence that could aid early identification of CI in MS and inform about new therapeutic targets and strategies.

The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis.

Oxidative stress markers have a distinct role in the process of demyelination in multiple sclerosis. This study investigated the potential correlation of markers of oxidative stress (glutathione [GSH], catalase) with the number of demyelinating lesions and the degree of disability, cognitive deficit, and depression in patients with relapsing-remitting multiple sclerosis (RRMS). Sixty subjects meeting the criteria for RRMS (19 men and 41 women), and 66 healthy controls (24 men, 42 women) were included. In this study, GSH significantly negatively correlated with the degree of cognitive impairment. This is the first study of subjects with RRMS that performed the mentioned research of serum GSH levels on the degree of cognitive damage examined by the Montreal Scale of Cognitive Assessment (MoCA) test. The development of cognitive changes, verified by the MoCA test, was statistically significantly influenced by the positive number of magnetic resonance lesions, degree of depression, expanded disability status scale (EDSS), age, and GSH values. Based on these results, it can be concluded that it is necessary to monitor cognitive status early in RRMS patients, especially in those with a larger number of demyelinating lesions and a higher EDSS level and in older subjects. Also, the serum level of GSH is a potential biomarker of disease progression, which could be used more widely in RRMS.

423 Innovation in MS Patient Care: Linking Cognitive Health and Myelin Integrity

OBJECTIVES/GOALS: Our objective is to develop a patient-friendly application addressing the progression of cognitive impairments in multiple sclerosis (MS) patients. This initiative aims to augment individualized care and precision management of a major MS comorbidity by generating a cognitive health brain map for each patient. METHODS/STUDY POPULATION: Using the UAMS COMS Database, featuring high-resolution multi-contrast MRIs, and a comprehensive clinical, behavioral, and demographic dataset, we are developing a hierarchical learning-based software tool to compute maps correlating brain structure-function and individual cognitive function. Our MRI analysis employs a three-compartment model (NNLS>0.96). Functional scores are defined by individualized accuracy during the modified information processing speed task (e.g., m-SDMT). We utilize a Bayesian classifier with explicit Pearson’s correlation for tissue classification (BF10>100) to compute an index of the likelihood of correlation with cognitive impairment throughout brain tissue. RESULTS/ANTICIPATED RESULTS: This approach allows us to reveal subtle cognitive changes and their potential links to myelin integrity, offering vital insights into disease progression and management. The m-SDMT strongly correlates with the standard SDMT (r=0.79, p<0.001), confirming reliability as a cognitive assessment tool in clinical and research contexts. Analysis of the COMS dataset emphasized insights into the role of fine myelin structure in MS patients' cognitive functionality. Our findings heightened the pivotal significance of myelin integrity in preserving cognitive abilities and identify disruptions in myelin synthesis and homeostasis as primary contributors to cognitive decline. This discovery stresses the critical role that specialized brain pathways, influenced by myelin integrity, play in the pathology of MS. DISCUSSION/SIGNIFICANCE: This development bridges advanced neuroimaging techniques with practical clinical applications, emphasizing the nuanced role of myelin integrity in MS-related cognitive deficits. Our findings advocate for a multidisciplinary approach to MS management, demanding collaborative workforce development and education in translational science.

Chronic Active Lesions and Larger Choroid Plexus Explain Cognition and Fatigue in Multiple Sclerosis.

Chronic inflammation may contribute to cognitive dysfunction and fatigue in patients with multiple sclerosis (MS). Paramagnetic rim lesions (PRLs) and choroid plexus (CP) enlargement have been proposed as markers of chronic inflammation in MS being associated with a more severe disease course. However, their relation with cognitive impairment and fatigue has not been fully explored yet. Here, we investigated the contribution of PRL number and volume and CP enlargement to cognitive impairment and fatigue in patients with MS. Brain 3T MRI, neurologic evaluation, and neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests and Modified Fatigue Impact Scale, were obtained from 129 patients with MS and 73 age-matched and sex-matched healthy controls (HC). PRLs were identified on phase images of susceptibility-weighted imaging, whereas CP volume was quantified using a fully automatic method on brain three-dimensional T1-weighted and fluid-attenuated inversion recovery MRI sequences. Predictors of cognitive impairment and fatigue were identified using random forest. Thirty-six (27.9%) patients with MS were cognitively impaired, and 31/113 (27.4%) patients had fatigue. Fifty-nine (45.7%) patients with MS had ≥1 PRLs (median = 0, interquartile range = 0;2). Compared with HC, patients with MS showed significantly higher T2-hyperintense white matter lesion (WM) volume; lower normalized brain, thalamic, hippocampal, caudate, cortical, and WM volumes; and higher normalized CP volume (p from <0.001 to 0.040). The predictors of cognitive impairment (relative importance) (out-of-bag area under the curve [OOB-AUC] = 0.707) were normalized brain volume (100%), normalized caudate volume (89.1%), normalized CP volume (80.3%), normalized cortical volume (70.3%), number (67.3%) and volume (66.7%) of PRLs, and T2-hyperintense WM lesion volume (64.0%). Normalized CP volume was the only predictor of the presence of fatigue (OOB-AUC = 0.563). Chronic inflammation, with higher number and volume of PRLs and enlarged CP, may contribute to cognitive impairment in MS in addition to gray matter atrophy. The contribution of enlarged CP in explaining fatigue supports the relevance of immune-related processes in determining this manifestation independently of disease severity. PRLs and CP enlargement may contribute to the pathophysiology of cognitive impairment and fatigue in MS, and they may represent clinically relevant therapeutic targets to limit the impact of these clinical manifestations in MS.

Resting-state functional imaging predictors of cognitive impairment in multiple sclerosis

Resting-state functional imaging predictors of cognitive impairment in multiple sclerosis

Regional GABA levels modulate abnormal resting-state network functional connectivity and cognitive impairment in multiple sclerosis.

More evidence shows that changes in functional connectivity with regard to brain networks and neurometabolite levels correlated to cognitive impairment in multiple sclerosis. However, the neurological basis underlying the relationship among neurometabolite levels, functional connectivity, and cognitive impairment remains unclear. For this purpose, we used a combination of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to study gamma-aminobutyric acid and glutamate concentrations in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus, and inter-network functional connectivity in 29 relapsing-remitting multiple sclerosis patients and 34 matched healthy controls. Neuropsychological tests were used to evaluate the cognitive function. We found that relapsing-remitting multiple sclerosis patients demonstrated significantly reduced gamma-aminobutyric acid and glutamate concentrations and aberrant functional connectivity involving cognitive-related networks compared to healthy controls, and both alterations were associated with specific cognition decline. Moreover, mediation analyses indicated that decremented hippocampus gamma-aminobutyric acid levels in relapsing-remitting multiple sclerosis patients mediated the association between inter-network functional connectivity in various components of default mode network and verbal memory deficits. In summary, our findings shed new lights on the essential function of GABAergic system abnormalities in regulating network dysconnectivity and functional connectivity in relapsing-remitting multiple sclerosis patients, suggesting potential novel approach to treatment.

Domain-specific cognitive impairment in multiple sclerosis: A systematic review and meta-analysis.

Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values. The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies." In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

Longitudinal fibre-specific white matter damage predicts cognitive decline in multiple sclerosis.

During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our understanding of cognitive impairment in multiple sclerosis may increase substantially. Accordingly, this study aimed to investigate specific patterns of white matter degeneration, the evolution over time, the manifestation across different stages of the disease and their role in cognitive impairment using a novel fixel-based approach. Neuropsychological test scores and MRI scans including 30-direction diffusion-weighted images were collected from 327 multiple sclerosis patients (mean age = 48.34 years, 221 female) and 95 healthy controls (mean age = 45.70 years, 55 female). Of those, 233 patients and 61 healthy controls had similar follow-up assessments 5 years after. Patients scoring 1.5 or 2 standard deviations below healthy controls on at least two out of seven cognitive domains (from the Brief Repeatable Battery of Neuropsychological Tests, BRB-N) were classified as mildly cognitively impaired or cognitively impaired, respectively, or otherwise cognitively preserved. Fixel-based analysis of diffusion data was used to calculate fibre-specific measures (fibre density, reflecting microstructural diffuse axonal damage; fibre cross-section, reflecting macrostructural tract atrophy) within atlas-based white matter tracts at each visit. At baseline, all fixel-based measures were significantly worse in multiple sclerosis compared with healthy controls (P < 0.05). For both fibre density and fibre cross-section, a similar pattern was observed, with secondary progressive multiple sclerosis patients having the most severe damage, followed by primary progressive and relapsing-remitting multiple sclerosis. Similarly, damage was least severe in cognitively preserved (n = 177), more severe in mildly cognitively impaired (n = 63) and worst in cognitively impaired (n = 87; P < 0.05). Microstructural damage was most pronounced in the cingulum, while macrostructural alterations were most pronounced in the corticospinal tract, cingulum and superior longitudinal fasciculus. Over time, white matter alterations worsened most severely in progressive multiple sclerosis (P < 0.05), with white matter atrophy progression mainly seen in the corticospinal tract and microstructural axonal damage worsening in cingulum and superior longitudinal fasciculus. Cognitive decline at follow-up could be predicted by baseline fixel-based measures (R2 = 0.45, P < 0.001). Fixel-based approaches are sensitive to white matter degeneration patterns in multiple sclerosis and can have strong predictive value for cognitive impairment. Longitudinal deterioration was most marked in progressive multiple sclerosis, indicating that degeneration in white matter remains important to characterize further in this phenotype.

Clinical features of sleep apnea syndrome and cognitive impairment in multiple sclerosis

Background: Complications of obstructive sleep apnea (OSA) have been reported in patients with multiple sclerosis (MS). Patients with sleep apnea syndrome (SAS) due to OSA also show cognitive decline, with similar clinical characteristics to that manifested in MS. SAS due to OSA is a treatable condition, and the associated cognitive decline is expected to improve. This study investigates clinical features of SAS in people living with MS and contribute to improve cognitive dysfunction of MS.Methods: A case-control study was conducted. Cognitive functions were evaluated by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test 2 (PASAT-2) and 3 (PASAT-3). The Respiratory Event Index (REI) was measured using Out of Center Sleep Testing (OCST). We defined subjects with REI ≥ 5 as OSA and divided participants into two groups with or without SAS due to OSA. Cognitive and respiratory characteristics were statistically compared between patients with MS and healthy controls.Results: We enrolled 67 people living with MS and 31 age- and sex-matched controls. OCST detected OSA in people living with MS and controls, and the prevalence rates were 28.4 % and 25.8 %, respectively. REI values (5.2 ± 7.9 vs 3.9 ± 5.2, p = 0.509) and number of participants with REI ≥ 5 (19 vs 8, p = 0.793) were similar between the MS and control group. The SDMT, PASAT-2, and PASAT-3 scores were significantly lower in the MS group than the control group (p < 0.001, p = 0.001, and p < 0.001, respectively). The interaction effect of MS and SAS on cognitive function was not significant in the SDMT (p = 0.078), but in the PASAT-2 (p = 0.043) and PASAT-3 (p = 0.020).Conclusion: This study revealed the prevalence rates of SAS in Japanese people living with MS and the usefulness of OCST for detection of SAS. This study also revealed that concomitant SAS can facilitate cognitive decline in people living with MS. These findings suggest that an appropriate intervention for OSA can be beneficial for people living with MS with cognitive decline.

Cognitive Impairment in Multiple Sclerosis: the Role of Sleep Disorders

Cognitive Impairment in Multiple Sclerosis: the Role of Sleep Disorders

The Association of ApoE Genotype and Cognitive Impairment in Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis

The Association of ApoE Genotype and Cognitive Impairment in Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis

Thalamic Atrophy, Duration of Illness, and Years of Education are the Best Predictors of Cognitive Impairment in Multiple Sclerosis

Thalamic Atrophy, Duration of Illness, and Years of Education are the Best Predictors of Cognitive Impairment in Multiple Sclerosis

Association of the BDNF rs6265 Polymorphism with Cognitive Impairment in Multiple Sclerosis: A Case-Control Study in Mexican Patients.

Cognition is a set of brain processes that allow the individual to interact with their environment. Multiple sclerosis (MS) is a chronic inflammatory disease that affects the cerebral white matter of the brain cortex and spinal cord, leading to cognitive impairment (CI) in 40-60% of the patients. Many studies have determined that CI is linked to genetic risk factors. We aimed to evaluate the association between BDNF gene rs6265 polymorphism and cognitive impairment in Mexican patients with MS by performing a case-control study. Mestizo-Mexican patients diagnosed with MS based on McDonald's criteria were enrolled. Cases were MS patients with CI (n = 31) while controls were MS patients without CI (n = 31). To measure cognitive functioning in MS patients, a neuropsychological screening battery for MS (NSB-MS) was used. Genotyping of the rs6265 gene variant was performed using quantitative real-time PCR (qPCR) with TaqMan probes. The results showed no statistically significant differences in sociodemographic and disease variables between case and control groups. qPCR analysis showed that there were 68% Val/Val wild-type homozygotes, 29% Val/Met polymorphic heterozygotes, and 3% Met/Met polymorphic homozygotes. The presence of BDNF gene rs6265 polymorphism showed an increased probability (3.6 times) of global cognitive impairment.

Exploring the Potential of the Corpus Callosum Area as a Predictive Marker for Impaired Information Processing in Multiple Sclerosis

Early cognitive impairment (CI) detection is crucial in multiple sclerosis (MS). However, it can progress silently regardless of relapse activity and reach an advanced stage. We aimed to determine whether the corpus callosum area (CCA) is a sensitive and feasible marker for CI in MS compared to other neuroimaging markers. We assessed cognitive function in 77 MS patients using the Symbol Digit Modalities Test, Paced Auditory Serial Additions Task, Wechsler Adult Intelligence Scale-IV, and Wechsler Memory Scale-Revised. The neuroimaging markers included manually measured CCA, two diffusion tensor imaging markers, and nine volumetric measurements. Apart from volumes of the hippocampus and cerebellum, ten markers showed a significant correlation with all neuropsychological tests and significant differences between the groups. The normalized CCA demonstrated a moderate-to-strong correlation with all neuropsychological tests and successfully differentiated between the CI and cognitively normal groups with 80% sensitivity and 83% specificity. The marker had a large area under the curve and a high Youden index (0.82 and 0.63, respectively) and comparability with established cognitive markers. Therefore, the normalized CCA may serve as a reliable marker for CI in MS and can be easily implemented in clinical practice, providing a supportive diagnostic tool for CI in MS.

The sequence of regional structural disconnectivity due to multiple sclerosis lesions.

Prediction of disease progression is challenging in multiple sclerosis as the sequence of lesion development and retention of inflammation within a subset of chronic lesions is heterogeneous among patients. We investigated the sequence of lesion-related regional structural disconnectivity across the spectrum of disability and cognitive impairment in multiple sclerosis. In a full cohort of 482 multiple sclerosis patients (age: 41.83 ± 11.63 years, 71.57% females), the Expanded Disability Status Scale was used to classify patients into (i) no or mild (Expanded Disability Status Scale <3) versus (ii) moderate or severe disability groups (Expanded Disability Status Scale ≥3). In 363 out of 482 patients, quantitative susceptibility mapping was used to identify paramagnetic rim lesions, which are maintained by a rim of iron-laden innate immune cells. In 171 out of 482 patients, Brief International Cognitive Assessment was used to identify subjects as being cognitively preserved or impaired. Network Modification Tool was used to estimate the regional structural disconnectivity due to multiple sclerosis lesions. Discriminative event-based modelling was applied to investigate the sequence of regional structural disconnectivity due to (i) all representative T2 fluid-attenuated inversion recovery lesions, (ii) paramagnetic rim lesions versus non-paramagnetic rim lesions separately across disability groups ('no to mild disability' to 'moderate to severe disability'), (iii) all representative T2 fluid-attenuated inversion recovery lesions and (iv) paramagnetic rim lesions versus non-paramagnetic rim lesions separately across cognitive status ('cognitively preserved' to 'cognitively impaired'). In the full cohort, structural disconnection in the ventral attention and subcortical networks, particularly in the supramarginal and putamen regions, was an early biomarker of moderate or severe disability. The earliest biomarkers of disability progression were structural disconnections due to paramagnetic rim lesions in the motor-related regions. Subcortical structural disconnection, particularly in the ventral diencephalon and thalamus regions, was an early biomarker of cognitive impairment. Our data-driven model revealed that the structural disconnection in the subcortical regions, particularly in the thalamus, is an early biomarker for both disability and cognitive impairment in multiple sclerosis. Paramagnetic rim lesions-related structural disconnection in the motor cortex may identify the patients at risk for moderate or severe disability in multiple sclerosis. Such information might be used to identify people with multiple sclerosis who have an increased risk of disability progression or cognitive decline in order to provide personalized treatment plans.

Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis.

Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25‑hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n=41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p=0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

Managing cognitive impairment and its impact in multiple sclerosis: An Australian multidisciplinary perspective.

Cognitive impairment in multiple sclerosis (MS) affects approximately 40-70% of patients and can have varying degrees of severity. Even mild cognitive impairment can impact on quality of life and productivity. Despite this, patients are not routinely screened or monitored for cognitive impairment in Australia due to a range of issues, with time and space being the main limiting factors. This Australian multidisciplinary perspective provides recommendations on cognition management in Australia. It gives a broad overview of cognition in MS, advice on the screening and monitoring tools available to clinicians, and strategies that can be implemented in clinics to help monitor for cognitive impairment in patients with MS. We suggest a routine baseline assessment and multidomain cognitive battery in regular intervals; a change should trigger a thorough investigation of the cause.

Does multilingualism act as a protective factor (cognitive reserve) against cognitive impairment in multiple sclerosis?: A retrospective cohort study

BackgroundCognitive impairment (CI) is common in multiple sclerosis (MS), affecting half of persons with MS (PwMS). Cognitive reserve has been associated with delaying the onset and slowing the progression of CI in PwMS. Multilingualism has been demonstrated to be a protective factor against CI in Alzheimer's disease (AD) but has never been studied in PwMS. ObjectiveTo explore if multilingualism is a protective factor against CI in PwMS. MethodsThis is a retrospective cohort study of PwMS aged 18–59, with a confirmed diagnosis of relapsing MS, fluent in English, who completed the Minimal Assessment of Cognitive Function in MS (MACFIMS) at the London (ON) MS Clinic. Any PwMS with a history of dementia or developmental delay, daily marijuana use, a major psychiatric disorder, or less than grade 9 education was excluded. We focused on the Brief Visuospatial Memory Test (BVMTR), immediate recall (-IR) and delayed recall (-DR) as it would be the least affected by language, as well as the Symbol Digit Modalities Test (SDMT), as information processing speed is the most commonly affected domain in PwMS. One-way ANOVA was used to compare raw scores on the BVMTR and SDMT between groups (uni- vs. multillingual), while chi-square was used to compare impairment on BVMTR and SDMT between groups. ResultsThe cohort consisted of 678 subjects. The mean age was 39.7 (± 9.6) years with 501 (73.9 %) females (sex at birth), the mean duration of disease of 5.9 (± 6.9) years, and mean years of education was 13.9 (±2.2). The majority of subjects (563, 83 %) were unilingual and (115, 17 %) were multilingual; 102 subjects were bilingual and 13 subjects fluent in ≥ three languages. English was the first language was in most of subjects (614, 90.6 %). There was no significant difference on the BVMTR-IR scores (p = 0.189) or BVMTR-DR (p = 0.096) between groups. Similarly, there was no difference in the number of subjects impaired on the BVMTR-IR (X2 (1, N = 678) = 3.167, p = 0.057) or BVMT-DR between groups (X2 (1, N = 678) = 2.996, p = 0.083). Further, there was no significant difference on the SDMT (p = 0.506) between groups, or in number of subjects impaired on the SDMT between groups (X2 (1, N = 678) = 1.023, p = 0.312). ConclusionThis study shows that multilingualism does not have a protective effect against CI in PwMS and does not play a role in enriching the cognitive reserve, in contrast to studies in AD. This difference may be explained by a different underlying pathological mechanism in these diseases and warrants further study.