Correlation between cognitive changes and neuroradiological changes over time in multiple sclerosis: a systematic review and meta-analysis.

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 (rs = 0.67, 95% CI 0.44-0.91), and verbal fluency and T2LV (rs = 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.

Diagnosis concealment behaviors and disclosure beliefs are associated with health and quality of life in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) struggle with whether, how, and how much to disclose their diagnosis. They often expend resources to conceal their diagnosis, and hold beliefs that it may negatively affect their personal relationships and/or professional opportunities. To better understand these effects, we developed a measure to quantify concealment behaviors and disclosure beliefs. Our main objective is to evaluate relationships of DISCO-MS responses to health and quality of life in a multinational cohort. METHODS: Survey responses were obtained for DISCO-MS and PROMIS-MS scales: global health, communication, social roles participation, anxiety, depression, emotional / behavioral dyscontrol, fatigue, lower extremity function, positive affect / well-being, social roles satisfaction, sleep, stigma, upper extremity function, cognitive function, bladder control, bowel control, visual function. Simple linear regression assessed associations. RESULTS: 263 pwMS were include. Higher concealment was associated with higher anxiety (beta= 0.15 [0.07, 0.23]), depression (beta = 0.13 [0.05, 0.21]), emotional dyscontrol (beta = 0.12 [0.04, 0.20]), lower affect / well-being (beta = -0.13 [-0.21, - 0.05]). Higher anticipation of negative consequences of disclosure was associated with lower self-reported physical (beta = -0.15) and mental health (beta = -0.14), lower positive affect / well-being, social roles satisfaction, higher anxiety, depression, emotional dyscontrol, sleep disturbance, and higher perceived stigma. DISCUSSION: These results reveal potential consequences of diagnosis concealment for physical and mental health and quality of life. Raising awareness and implementing interventions may mitigate negative repercussions of concealment.

Sex differences in brain resilience of individuals with multiple sclerosis.

BACKGROUND: Brain resilience allows maintenance of neurocognitive function in the face of age or disease-related neural changes. OBJECTIVE: Test the hypothesis that women and men with MS differ in brain resilience. METHODS: This cross-sectional analysis of prospective cohort data included 11,297 patients. Linear mixed effects models predicted performance outcomes on tasks of fine motor dexterity and cognitive processing speed for MRI proxies of disease burden: brain parenchymal fraction (BPF), T2 lesion volume, volumes of deep gray, thalamus, white and cortical gray matter. Covariates were age, sex, age-by-sex, current disease-modifying therapy, disease phenotype, education, total brain volume, and total brain volume-by-sex. Sex-by-MRI metric terms tested primary hypothesis of differential brain-behavior relationships between men and women. RESULTS: Final sample included 10,286 participants. Lower BPF was associated with worse performance (p's<0.001) in men and women; association was smaller for women than men for processing speed (ßetaWomen-Men=-0.044, 95 % CI=[-0.087, -0.002], p = 0.041) and manual dexterity (ßetaWomen-Men=-0.073, 95 % CI=[-0.124, -0.023], p = 0.005). For each MRI variable, women demonstrated better neurocognitive function controlling for disease burden. DISCUSSION: Sex differences in brain metric-neurofunctional performance relationships of people with MS suggest women have higher resilience than men in the face of increased disease burden. Future work exploring mechanism is warranted.

Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies.

BACKGROUND: Current treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. OBJECTIVE: Determine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. METHODS: In cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). RESULTS: Controlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). CONCLUSIONS: Women and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.

A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

Brain volumetric correlates of remotely versus in-person administered symbol digit modalities test in multiple sclerosis.

BACKGROUND: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person. METHODS: SDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3-dimensional T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure having SDMT scores as the outcome variable in each model. In addition, the correlation and average difference between In-person and Remote group associations across the MRI measures were calculated. Finally, for each MRI variable I2 score was quantified to test the heterogeneity between the groups. RESULTS: Administration modality did not affect the association of SDMT performance with MRI measures. Brain tissue volumes showing high associations with the SDMT scores in one group also showed high associations in the other (r = 0.83; 95% CI = [0.07, 0.86]). The average difference between the In-person and the Remote group associations was not significant (ßRemote - ßIn-person = 0.14, 95% CI = [-0.04, 0.34]). Across MRI measures, the average I2 value was 14%, reflecting very little heterogeneity in the relationship of SDMT performance to brain volume. CONCLUSION: We found consistent relationships to neural correlates across in-person and remote SDMT administration modalities. Hence, our study extended the findings of the previous studies demonstrating the feasibility of remote administration of the SDMT.

Feasibility trial of a telehealth support group intervention to reduce anxiety in multiple sclerosis.

OBJECTIVE: Anxiety is common among persons with MS (PwMS), but widely accepted treatments are lacking. Group-based interventions delivered via telehealth are an accessible treatment option requiring clinical trial evidence to support feasibility and initial efficacy. We conducted a pilot feasibility trial of an online support group intervention to reduce anxiety in PwMS. METHODS: A non-randomized, parallel arm clinical trial was conducted. A total of 31 PwMS were enrolled: 20 completed a 12-week telehealth-delivered support group intervention and 11 were assigned to a survey-only control group. Primary feasibility outcomes were adherence and completion rates. Primary efficacy outcome was anxiety, secondary outcomes were depression, loneliness, distress, self-efficacy, stress, and quality of life. RESULTS: Twenty-six participants completed the study. Intervention group adherence (75%) and completion (85%) rates were acceptable. Results indicated a medium size between-group effect, suggesting a greater reduction in anxiety in the intervention group compared to the control group [U = 39.50, p = 0.045, r = 0.39]. No group differences in other outcomes were observed. CONCLUSION: A telehealth-delivered support group intervention appears feasible for further study and shows initial efficacy for the reduction of anxiety in PwMS.

Summary metrics of memory subnetwork functional connectivity alterations in multiple sclerosis.

BACKGROUND: Memory dysfunction is common in multiple sclerosis (MS); mechanistic understanding of its causes is lacking. Large-scale network resting-state functional connectivity (RSFC) is sensitive to memory dysfunction. OBJECTIVE: We derived and tested summary metrics of memory network RSFC. METHODS: Cognitive data and 3T magnetic resonance imaging (MRI) scans were collected from 235 MS patients and 35 healthy controls (HCs). Index scores were calculated as RSFC within (anteriority index, AntI) and between (integration index, IntI) dorsomedial anterior temporal and medial temporal memory subnetworks. Group differences in index expression were evaluated. Associations between index scores and memory/non-memory cognition were evaluated; relationships between T2 lesion volume (T2LV) and index scores were assessed. RESULTS: Index scores were related to memory and T2LV in MS patients, who showed marginally elevated AntI relative to HC (p = 0.06); no group differences were found for IntI. Better memory was associated with higher AntI (ß = 0.15, p = 0.018) and IntI (ß = 0.16, p = 0.014). No associations were found for non-memory cognition. Higher T2LV was associated with higher AntI and IntI; exploratory mediation analysis revealed significant inconsistent mediation, that is, higher index scores partially suppressed the negative association between T2LV and memory. CONCLUSION: Summary, within-subject metrics permit replication and circumvent challenges of traditional (incommensurate) RSFC variables to advance development of mechanistic models of memory dysfunction in MS.

Association of personality traits with physical function, cognition, and mood in multiple sclerosis.

BACKGROUND: Growing literature supports the hypothesis that personality influences health outcomes. Few studies have examined the association between personality traits and key clinical manifestations in persons with multiple sclerosis (pwMS). OBJECTIVE: To investigate whether personality traits are associated with physical function, cognition, and depression in persons with MS. METHODS: In this cross-sectional study, we analyzed data from two cohorts (UPMC, n = 365 and CUIMC, n = 129). Participants completed a personality scale (assessing neuroticism, extraversion, openness, agreeableness, and conscientiousness) and validated surveys measuring physical function, cognition, and depression. Stepwise linear regressions were used to evaluate associations between personality traits and outcome measures. RESULTS: Consistently across cohorts, higher extraversion was associated with better physical function, whereas higher neuroticism was associated with worse depression. In the first cohort, higher extraversion was associated with better cognition, while higher neuroticism was associated with greater risk for memory impairment in the second cohort. Relationships were independent of age and disease duration. CONCLUSION: Findings suggest a potentially protective role of extraversion, and a harmful role of neuroticism, in MS-specific patient-reported clinical outcomes. Increased understanding of the interplay between personality and health outcomes may inform risk models for physical decline, cognitive impairment, and depression in pwMS.

Diagnosis concealment is associated with psychosocial outcomes in persons with multiple sclerosis.

Persons with multiple sclerosis (pwMS) frequently conceal their diagnosis, fearing professional and personal repercussions of disclosing. Associations of concealment behavior and expected consequences of disclosure with psychosocial outcomes were examined in 90 pwMS who completed validated self-report measures of diagnosis concealment, loneliness, social support, and self-efficacy. More frequent concealment was related to worse loneliness (rp = 0.213, p = 0.045) and lower social support (rp = -0.211, p = 0.047), controlling for depression. Higher anticipated negative consequences of disclosure were associated with worse loneliness (rp = 0.263, p = 0.013), lower social support (rp = -0.338, p < 0.001), and lower self-efficacy (rp = -0.350, p < 0.001). Findings hold implications for the development of psychological support strategies addressing concealment/disclosure issues and their psychosocial consequences.

It's time to talk about disclosure and concealment in MS.

Deciding when and if to disclose a diagnosis of multiple sclerosis (MS) is complicated and highly stressful for individuals who are already facing many challenges. To date, few research studies have explored specific ways in which this challenge affects people with MS. From a cognitive neuroscience standpoint, the brain is a limited capacity system whereby any allocation of resources has a consequence for overall brain efficiency. To better understand the consequences of allocating resources to concealment behaviors and disclosure decisions, we developed a measurement tool, the DISCO-MS. Here, we discuss insights gained from follow-up focus group discussions with MS patients.

Assessing diagnosis disclosure and concealment in multiple sclerosis: Development and initial validation of the DISCO-MS survey.

BACKGROUND: Individuals with multiple sclerosis (MS) regularly report making strategic decisions about whether to share their diagnosis or keep it a secret; for many, this represents a key stressor. Surprisingly, the impact of disclosure and concealment are understudied in MS and a formal measurement instrument is lacking. We developed the Diagnosis Disclosure and Concealment in MS (DISCO-MS) survey, a self-assessment tool evaluating (1) frequency of concealment behaviors and (2) expected consequences of diagnosis disclosure in persons with MS. METHODS: A systematic mixed-methods process was used for the design and initial validation of the DISCO-MS. Associations of DISCO-MS responses to demographics, clinical variables, and mood were examined in 204 participants with MS. RESULTS: The 39-item DISCO-MS shows good psychometric characteristics. Approximately 25% of respondents conceal their diagnosis, particularly in professional settings. Higher concealment behaviors were associated with younger age, shorter disease duration, and lower physical disability. Nearly 50% of respondents believed that talking openly about their diagnosis might have undesirable professional and interpersonal consequences. Younger age, higher depression, and higher anxiety were associated with greater expectations of negative consequences. CONCLUSION: Development and validation of the DISCO-MS presents the first step toward systematic study of the impact of DISCO on people with MS.

Associations of social network structure with cognition and amygdala volume in multiple sclerosis: An exploratory investigation.

BACKGROUND: Humans are inherently social, biologically programmed to connect with others. Social connections are known to impact mental and physical health. OBJECTIVE: The aim of this study was to test whether social network structure is linked to cognition, mood, fatigue, and regional brain volumes in persons with multiple sclerosis (MS). METHODS: A questionnaire quantifying individual-level social network structure (size, density, effective size, and constraint), a comprehensive battery of neuropsychological tests, and magnetic resonance imaging (MRI) was administered to 51 persons with relapsing-remitting MS. Linear regressions assessed associations of network variables to cognition, depression, fatigue, and structural brain volumes. RESULTS: Higher network density and constraint, indicating stronger connections among network members, were associated with worse language functions. Conversely, larger network effective size, a measure of non-redundant network members, was associated with better language functions. No relationships of network structure to depression or fatigue were found. Larger network size was related to larger amygdala volume. CONCLUSION: Findings suggest that social network structure is linked to language function and amygdala volume in persons with MS. Patients with close-knit networks showed worse language function than those with open networks. Longitudinal studies with larger samples are warranted to evaluate potential causal links between social network structure and MS-related cognitive impairment.

Machine learning to investigate superficial white matter integrity in early multiple sclerosis.

BACKGROUND AND PURPOSE: This study aims todetermine the sensitivity of superficial white matter (SWM) integrity as a metric to distinguish early multiple sclerosis (MS) patients from healthy controls (HC). METHODS: Fractional anisotropy and mean diffusivity (MD) values from SWM bundles across the cortex and major deep white matter (DWM) tracts were extracted from 29 early MS patients and 31 age- and sex-matched HC. Thickness of 68 cortical regions and resting-state functional-connectivity (RSFC) among them were calculated. The distribution of structural and functional metrics between groups were compared using Wilcoxon rank-sum test. Utilizing a machine learning method (adaptive boosting), 6 models were built based on: 1-SWM, 2-DWM, 3-SWM and DWM, 4-cortical thickness, or 5-RSFC measures. In model 6, all features from previous models were incorporated. The models were trained with nested 5-folds cross-validation. Area under the receiver operating characteristic curve (AUCroc ) values were calculated to evaluate classification performance of each model. Permutation tests were used to compare the AUCroc values. RESULTS: Patients had higher MD in SWM bundles including insula, inferior frontal, orbitofrontal, superior and medial temporal, and pre- and post-central cortices (p < .05). No group differences were found for any other MRI metric. The model incorporating SWM and DWM features provided the best classification (AUCroc = 0.75). The SWM model provided higher AUCroc (0.74), compared to DWM (0.63), cortical thickness (0.67), RSFC (0.63), and all-features (0.68) models (p < .001 for all). CONCLUSION: Our results reveal a non-random pattern of SWM abnormalities at early stages of MS even before pronounced structural and functional alterations emerge.

RCT of a Telehealth Group-Based Intervention to Increase Physical Activity in Multiple Sclerosis: eFIT.

OBJECTIVE: To conduct a pilot randomized controlled trial to determine whether participation in a group-based structured telehealth intervention increases physical activity in people with multiple sclerosis (MS). METHODS: In this parallel-arms trial, all study procedures were administered remotely. Adults diagnosed with MS (any subtype) were randomized to one of two 12-week (1 h/wk) active conditions: eFIT, online moderated structured groups; or eJournal, online independent journaling. For comparison, a treatment-as-usual (TAU; i.e., no eFIT/eJournal) group was enrolled. The primary outcome was feasibility (completion and adherence). The secondary efficacy outcomes included self-reported physical activity level (International Physical Activity Questionnaire, IPAQ). RESULTS: Participants were 37 adults with MS. The sample was diverse: 66.7% female; age range 23-64 years; 17.5% Hispanic, 12.5% Black; and progressive and relapsing-remitting disease subtypes. Regarding feasibility, 70.7% completed; average adherence was 74.9%. Physical activity in active groups increased by 34.2% (baseline IPAQ = 2,406.8 ± 1,959.7, follow-up = 3,229.4 ± 2,575.2) and decreased in the TAU group by 17.4% (baseline = 2,519.9 ± 1,500.1, follow-up = 2,081.2 ± 1,814.9); group × time interaction was not statistically significant [F(2,25) = 1.467, p = 0.250; partial η2 = 0.105]. CONCLUSIONS: Telehealth represents an accessible, acceptable vehicle to deliver targeted behavioral treatments to a neurologic population. eFIT may be an effective intervention for increasing physical activity, a historically intractable treatment target, in individuals with MS. In addition, these results provide evidence for feasibility of conducting fully remote clinical trial research. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with MS, participation in a group-based structured telehealth intervention compared with TAU resulted in a (non-significant) increase in self-reported physical activity level. The percentage of participants who completed follow-up questionnaires did not differ between groups. The trial was registered at ClinicalTrials.gov (NCT03829267).

Dietary factors and MRI metrics in early Multiple Sclerosis.

BACKGROUND: Despite significant interest in diet by the MS community, research on this topic is limited; there are no published studies evaluating associations between diet and neuroimaging in MS. METHODS: We utilized baseline data from the RADIEMS cohort of early MS (diagnosed <5.0 years, n=180). Participants underwent brain MRIs to derive normalized total gray and thalamic volumes, T2 lesion volume, and white matter microstructural integrity of normal appearing white matter (NAWM). Participants completed food frequency questionnaires (FFQ) from which we calculated adherence scores to pre-specified dietary patterns including the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We evaluated intake of the following pre-specified dietary components: fruits, vegetables, legumes, nuts, whole grains, dairy, fried foods, processed meats, and fat intake. We used multivariable-adjusted linear regression to evaluate MRI metrics versus dietary measures. RESULTS: MIND diet score was associated with thalamic volume; individuals in the highest quartile of MIND diet scores had greater thalamic volumes versus those in the lowest quartile (Q4 vs. Q1: 1.03mL; 95%CI: 0.26mL, 1.79mL; p<0.01). For individual food/nutrients, higher intakes of full-fat dairy were associated with lower T2 lesion volumes (Q4 vs. Q1: -0.93mL; 95%CI: -1.51mL, -0.35ml; p<0.01). Higher intakes of marine omega-3 fatty acids were associated with greater NAWM microstructural integrity (Q4 vs. Q1: 0.40; 95%CI: 0.03, 0.76; p=0.04). Other foods/nutrients were not associated with MRI outcomes. CONCLUSIONS: In this first study focused on neuroimaging and diet in MS, we note significant associations in a cross-sectional early MS cohort. Longitudinal follow-up of imaging/clinical outcomes will provide additional insights.

Sleep disturbance and memory dysfunction in early multiple sclerosis.

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.