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Traditional in-person neuropsychological tests remain inaccessible and not adapted to individuals in remote geographical locations and linguistically diverse populations. We aimed to make neuropsychological tests more accessible and adapted to diverse populations by leveraging the internet. We examined the feasibility, discriminability, and generalizability of the Montreal Cognitive Assessment-video conferencing version (MoCA-VC) across geographically and linguistically diverse populations. We tested 250 participants from 120+ locations in the USA and Israel, using a standardized MoCA-VC protocol in English, Hebrew, or Arabic. Performance followed expected significant trends across language-speaking cohorts: young adults (YA)>older adults (OA)>people with Parkinson’s Disease (PwP), confirming discriminative abilities. However, while the YA groups performed similarly across the three language-speaking cohorts, the OA and PwP Arabic-speaking cohorts demonstrated significantly lower scores, indicating limited generalizability. While these findings support MoCA-VC’s feasibility and discriminability, they underscore the need to adapt online cognitive assessments across geographical locations and languages, ensuring greater accessibility worldwide.

Cognitive impairment is common among persons with multiple sclerosis (MS), but some patients are able to withstand considerable disease burden (e.g. white matter lesions, cerebral atrophy) without cognitive impairment (cognitive inefficiency, memory decline). What protects these patients from cognitive impairment? We review the literature on cognitive reserve in MS, which shows that heritable (larger maximal lifetime brain growth) and environmental (greater intellectual enrichment) factors attenuate the negative effect of disease burden on cognitive status. That is, persons with larger maximal lifetime brain growth, greater vocabulary knowledge, and/or greater early life participation in cognitive leisure activities (e.g. reading, hobbies) are better able to cope with MS disease without cognitive impairment. We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.

Background While many studies have examined relationships of neuroimaging variables to cognitive measures in multiple sclerosis (MS), longitudinal studies are lacking. The relationship of cognitive changes to neuroradiological changes in MS is thus incompletely understood. The present study systematically reviews all studies reporting a relationship between MRI changes and cognitive changes after at least one year of follow-up. Method An extensive and methodical search of online databases was conducted to identify qualified studies until August 2023. Among various cognitive tests and magnetic resonance imaging (MRI) measures, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), verbal fluency, T2 lesion volume (T2LV), white matter lesion volume (WML), and grey matter volume (GMV) qualified for inclusion in a meta-analysis investigating the association of cognitive changes to neuroradiological changes. Results We identified 35 studies that explored the link between MRI changes and changes in cognitive outcomes. Of these, twenty studies (57.14%) investigated the association between SDMT/PASAT and MRI metrics. Eleven studies (31.42%) focused on the relationship between MRI metrics and verbal learning and memory, while ten studies (28.57%) reported associations with visuospatial learning and memory. Furthermore, eight studies (22.85%) analyzed the correlation between verbal fluency and MRI measures. Only 5 were eligible for inclusion in the meta-analysis. The meta-analysis evaluated correlations between SDMT/PASAT and GMV ( r s  = 0.67, 95% CI 0.44–0.91), and verbal fluency and T2LV ( r s  = 0.35, 95% CI 0.09–0.60). Conclusion In this rigorously conducted systematic review, we found a significant association of cognitive changes, specifically SDMT/PASAT and verbal fluency, to changes in T2LV and atrophy in individuals with MS. Findings should be interpreted cautiously due to the limited amount of high-quality research, small sample sizes, and variability in study methodologies.

Background Resilience is a protective factor that emerges when individuals are faced with challenges and stressors. Multiple sclerosis (MS) is a chronic neurological disease that introduces a great deal of stress for the individual and his/her support partner. We designed a telehealth resilience-building dyadic program for persons with MS (PwMS) and their support partners. Objectives To evaluate the feasibility of the resilience intervention. The secondary objective was to assess the benefits of the intervention. Methods Sixty-two participants (M = 49.5 years, 31 dyads of PwMS) and support partners) were recruited to participate. Out of the 31 dyads, 26 were spouses, 2 were cohabiting partners, and 3 were parent–child dyads. Results The feasibility goals of the intervention were met, as determined by high participant satisfaction and acceptable completion rates. Preliminary outcomes relating to resilience were positive, suggesting that this intervention had a positive impact on participants. Conclusions To the best of our knowledge, this is the first resilience-building intervention delivered via telehealth for both PwMS and their support partners. The study showed an increase in resilience-building skills for addressing the challenges faced by PwMS and their support partners. These skills can be promoted and taught, clinically supported by telehealth, an affordable, accessible healthcare solution. Trial Registration at ClinicalTrials.gov (NCT03555253).

BackgroundCognitive impairment is a debilitating symptom experienced by ~ 50% of multiple sclerosis patients, with processing speed (PS) and memory most affected. Until now, the field has considered cognition in a binary fashion: patients are designated as impaired or not impaired. This designation is typically arrived at by administering a full cognitive battery and assigning a cutoff (e.g., 4 of 11 tests failed) to distinguish impaired/non-impaired. This relatively coarse approach yields a heterogeneous group of “impaired” patients, some of whom may have isolated memory or PS deficits, others with combined deficits. The goal of this study is to determine whether predominant patterns of deficits, “cognitive phenotypes”, can be identified in a large sample of MS patients. Proportional representation of four cognitive phenotypes will be evaluated: (1) not impaired, (2) PS-impaired only, (3) memory-impaired only, (4) PS + memory impaired.MethodsCognition was measured in 128 relapsing–remitting MS patients using validated tests of verbal/visual memory, and PS. Cognitive phenotype representation was evaluated. Differences in age, education, disease duration, and IQ across cognitive phenotype groups were evaluated.ResultsFour cognitive phenotype groups were represented: 56.3% not impaired, 7.8% PS-impaired, 18.8% memory-impaired, 17.2% PS + memory impaired. Across groups, there were no differences in age, education, disease duration. IQ in non-impaired was higher than PS + memory impaired.ConclusionsAdopting a novel classification taxonomy for cognitive phenotypes will advance understanding of cognitive impairment and enable a precision medicine approach to the development of effective, targeted treatments for cognition in persons with MS.

IntroductionThe many benefits of exercise for persons with multiple sclerosis (MS) are well established, yet patients often refrain from exercise due to overheating and exhaustion. The present randomised controlled trial tests aspirin (acetylsalicylic acid (ASA)) as a convenient method to prevent overheating and improve exercise performance in persons with MS. The effects of ASA are compared with those of acetaminophen (APAP) and placebo.Methods and analysisParticipants are seen for a laboratory maximal exercise test on 3 separate days separated by at least 1 week. At each session, body temperature is measured before oral administration of a standard adult dose (650 mg) of ASA, APAP or placebo. One hour after drug administration, participants perform a maximal ramp test on a cycle ergometer. Primary outcomes are (a) time to exhaustion (that is, time spent cycling to peak exertion) and (b) body temperature change. Crossover analyses will include tests for effects of treatment, period, treatment–period interaction (carryover effect) and sequence.Ethics and disseminationEthical approval was granted by the institutional review board at Columbia University Irving Medical Center (reference: AAAS2529). Results of the trial will be published in peer-reviewed scientific journals and presented at national and international conferences. Neurologists, physiatrists, primary care physicians and physiotherapists are important stakeholders and will be targeted during dissemination. Positive trial results have the potential to promote aspirin therapy, an inexpensive and readily available treatment, to reduce overheating and allow more persons with MS to benefit from exercise.Trial registration numberNCT03824938.

Multiple sclerosis is a neurological disease that involves white matter lesions throughout the brain, and depression is a common comorbidity. In this paper, Siddiqi, Kletenik et al. propose the use of a recently developed technique known as lesion network mapping to identify a common depression network that may represent a treatment target for neuromodulatory approaches to treating depression.

Objective Sleep‐dependent memory processing occurs in animals including humans, and disturbed sleep negatively affects memory. Sleep disturbance and memory dysfunction are common in multiple sclerosis (MS), but little is known about the contributions of sleep disturbance to memory in MS. We investigated whether subjective sleep disturbance is linked to worse memory in early MS independently of potential confounders. Methods Persons with early MS (n = 185; ≤5.0 years diagnosed) and demographically matched healthy controls (n = 50) completed four memory tests to derive a memory composite, and four speeded tests to derive a cognitive efficiency composite. Z‐scores were calculated relative to healthy controls. Sleep disturbance was defined by the Insomnia Severity Index score ≥ 10. ANCOVAs examined differences in memory and cognitive efficiency between patients with and without sleep disturbance controlling for potential confounds (e.g., mood, fatigue, disability, T2 lesion volume, gray matter volume). Comparisons were made to healthy controls. Results Seventy‐four (40%) patients reported sleep disturbance. Controlling for all covariates, patients with sleep disturbance had worse memory (z = −0.617; 95% CI: −0.886, −0.348) than patients without disturbance (z = −0.171, −0.425, 0.082, P = .003). Cognitive efficiency did not differ between groups. Relative to healthy controls, memory was worse among patients with sleep disturbance, but not among patients without sleep disturbance. Interpretation Sleep disturbance contributes to MS memory dysfunction, which may help explain differential risk for memory dysfunction in persons with MS, especially since sleep disturbance is common in MS. Potential mechanisms linking sleep disturbance and memory are discussed, as well as recommendations for further mechanistic and interventional research.

Objective To report initial results of a planned multicenter year‐long prospective study examining the risk and impact of COVID‐19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). Methods In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID‐19 in persons with NID (PwNID) and change in their neurological care. Results Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID‐19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID‐19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID‐19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID‐19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID‐19 (ORadj = 1.45, 1.17–1.84). Interpretations Our study of real‐time, patient‐reported experience during the COVID‐19 pandemic complements physician‐reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID‐19 similar to the reference population.

ObjectiveTo investigate associations of social support to psychological well-being, cognition, and motor functioning in patients with multiple sclerosis (MS). Secondarily, we were interested in exploring sex differences in these relationships, based on a bioevolutionary theoretical justification.MethodsSocial support was assessed in 185 recently diagnosed patients (RADIEMS cohort), and in an independent validation sample (MEMCONNECT cohort, n = 62). Patients also completed a comprehensive neurobehavioral evaluation including measures of mental health, fatigue, quality of life, cognition, and motor function. Correlations tested links between social support and these variables, along with potential gender differences.ResultsIn both samples, higher social support was associated with better mental health, quality of life, subjective cognitive function, and less fatigue. In the RADIEMS cohort, higher social support was associated with better motor functions, particularly grip strength and gait endurance in women.ConclusionsThese findings highlight associations of social support to overall psychological health and motor functioning in persons with MS, underlining the potential opportunity of evaluating and promoting social engagement in novel treatment strategies.