Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study.

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = -.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.

Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis.

BACKGROUND: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose. OBJECTIVE: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements. METHODS: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials. RESULTS AND CONCLUSION: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Reasons for nonadherence and response to treatment in an adherence intervention trial for relapsing-remitting multiple sclerosis patients.

OBJECTIVES: To explore whether patients in an adherence trial who appeared not to take disease modifying therapy (DMT) for avoidance reasons could be reliably identified, by observational coding, for their main reason of not taking DMT. To determine whether reason groups could be distinguished by clinical and self-report psychological characteristics and intervention outcomes. METHOD: Participants were multiple sclerosis patients (N = 78, 88.5% female, mean age 45.64) demotivated to take DMT. Audio recordings of the sessions were coded for the main reason of not taking DMT. Reason groups were compared based on patient characteristics and intervention outcomes. RESULTS: Avoidance and three other reasons for not taking DMT (side effects, cost, and mild course) were reliably identified (κ = 0.88). Patient characteristics failed to distinguish participants in the Avoidance group, which also had poorer outcomes (X2 [2, n = 73] = 6.35, p = 0.036). CONCLUSIONS: Patients not taking DMT for avoidance reasons may need novel methods to identify them and encourage (re-)initiation.

Baseline predictors of DMT reinitiation among patients with multiple sclerosis following an MI-CBT intervention.

Patients with multiple sclerosis (MS) are often nonadherent to their disease modifying therapy (DMT). While recent studies demonstrate enhanced DMT adherence following intervention grounded in motivational interviewing (MI), little is known about how to address DMT reinitiation among MS patients who have prematurely discontinued DMT against medical advice and do not intend to reinitiate. We examined baseline predictors of DMT reinitiation among patients with MS who discontinued medications against medical advice following a telephone-based MI and Cognitive Behavioral Therapy (MI-CBT) intervention. Following MI-CBT intervention, 66 patients reported whether or not they opted to reinitiate DMT. Rate of disease progression (ß = 0.295) and perceived personal control (ß = - 0.131) emerged as unique significant predictors of DMT reinitiation following intervention. Clinical characteristics and health-related beliefs may be used to prospectively identify patients most likely to reinitiate DMT following MI-CBT intervention, furthering the goal of preserving brain health and preventing neurologic decline in MS via appropriate DMT utilization. Further study is warranted to delineate potential mediators and moderators of DMT reinitiation outcomes.

Randomized Controlled Trial to Improve Self-Efficacy in People With Multiple Sclerosis: The Community Reintegration for Socially Isolated Patients (CRISP) Program.

OBJECTIVE: We examined the efficacy of a 12-wk educational socialization program, Community Reintegration for Socially Isolated Patients (CRISP), in improving self-efficacy for people with multiple sclerosis (MS). We also examined whether participants in the experimental group with increased self-efficacy experienced reduced loneliness and depression. METHOD: This randomized controlled group design included 91 participants with MS (experimental group, n = 51; control group, n = 40). Participants were between ages 20 and 68 yr, and the majority experienced a relapsing-remitting MS course (86%) and mild to moderate disability. Participants completed baseline and posttreatment assessments, including questionnaires assessing self-efficacy, loneliness, and depression. RESULTS: Experimental group participants significantly improved in self-efficacy compared with control group participants. Experimental group participants who demonstrated improved self-efficacy reported reduced perceptions of loneliness but not depressive symptoms. CONCLUSION: CRISP is a promising intervention to improve self-efficacy for people with MS. However, results need to be treated with caution given the study's limitations.

Being Kind to Your Future Self: Probability Discounting of Health Decision-Making.

INTRODUCTION: Nearly 50 % of patients with chronic medical illness exhibit poor treatment adherence. When making treatment decisions, these patients must balance the probability of current side effects against the probability of long-term benefits. This study examines if the behavioral economic construct of probability discounting can be used to explain treatment decisions in chronic disease. METHODS: Thirty-eight nonadherent and 39 adherent patients with multiple sclerosis (MS) completed a series of hypothetical treatment scenarios with varied risk and benefit probabilities. RESULTS: As described by a hyperbolic probability discounting model, all patients reported decreased medication initiation as the probability of treatment efficacy decreased and the probability of treatment side effects increased. When compared to adherent patients, nonadherent patients significantly devalued treatment efficacy and inflated treatment risk. DISCUSSION: The methods in this study can be used to identify optimal risk/benefit ratios for treatment development and inform the process by which patients make treatment decisions.

A pilot study to improve adherence among MS patients who discontinue treatment against medical advice.

Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690.

Factors That Moderate Activity Limitation and Participation Restriction in People With Multiple Sclerosis.

We examined the variables most associated with activity limitation (i.e., cooking) and participation restriction (i.e., employment) in 72 people with multiple sclerosis (MS). Participants underwent a comprehensive neuropsychological test battery assessing memory, executive functions, visual perception, and processing speed and completed questionnaires assessing activity, participation, fatigue, and affective symptoms. Results showed that processing speed was the only variable consistently significantly related to both activity and participation. When examining specific aspects of activity and participation in isolation, employment status was significantly associated with education level, visual memory, fatigue, and processing speed. Cooking ability was associated with performance on tasks of working memory, verbal memory, and processing speed. These findings suggest that processing speed is a primary cognitive factor in MS influencing quality of both activity and participation in everyday life.

Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing.

Unemployment is a significant concern among individuals with multiple sclerosis (MS). Determinations regarding ability to work are highly dependent on measurement tools used by neurologists and allied professionals. However, little is known of the usefulness of these tools when determining issues pertaining to employment status. The purpose of the present investigation was to examine the utility of the Multiple Sclerosis Functional Composite (MSFC) and a brief cognitive test battery when examining employment status in MS. Seventy-seven individuals with MS completed the MSFC and a brief cognitive test battery. On the MSFC, unemployed individuals demonstrated worse upper extremity functioning. There was no difference on the Paced Auditory Serial Addition Task (PASAT), the sole cognitive measure of the MSFC. On cognitive testing, unemployed individuals performed worse on measures of memory, information processing speed, and executive functioning. Through logistic regression analysis, the Symbol Digit Modalities Test (SDMT) was found to be the sole predictor of employment status among the significant disease, MSFC and cognitive variables. Consistent with previous findings, logistic regression found the SDMT to be a significant predictor of employment status. Given the lack of significant group differences on the PASAT, continued consideration of replacing the PASAT with the SDMT in the MSFC appears warranted.

Coping and psychological well-being among persons with relapsing-remitting multiple sclerosis: The role of perceived self-efficacy.

OBJECTIVE: To explore self-efficacy as a possible mediator in the relationship between adaptive coping and psychological well-being (PWB) in persons with relapsing-remitting multiple sclerosis (RRMS). METHOD: 174 persons with RRMS (91% Female) completed an online survey consisting of psychosocial questionnaires. The COPE Inventory was used to create an adaptive coping composite that accounts for the relative contributions of both active and avoidant coping. Self-efficacy was measured using the General Self-Efficacy Scale. The Ryff Psychological Well-Being Scales captured several domains of PWB: Positive relations with others, autonomy, purpose in life, environmental mastery, self-acceptance, and personal growth. The SPSS PROCESS macro was used to test whether self-efficacy mediated the association between adaptive coping and each PWB subscale, using 5,000 bootstrap samples to estimate confidence intervals. RESULTS: In each mediational model, adaptive coping was significantly associated with each PWB subscale and self-efficacy (all p's ≤ 0.001). Self-efficacy was also significantly associated with each PWB subscale (p ≤ 0.001). After controlling for self-efficacy, the associations between adaptive coping and positive relations with others (indirect effect = 0.021, 95% CI [0.011, 0.033]) and autonomy (indirect effect = 0.019, 95% CI [0.011, 0.028]) became non-significant. The separate associations between adaptive coping and purpose in life (p = .004), self-acceptance (p = .026), and personal growth (p < .001) remained significant, despite controlling for self-efficacy. CONCLUSIONS: Self-efficacy fully mediated the relationships between adaptive coping and positive relations with others and autonomy in our sample of persons with RRMS. Interventions aimed at increasing adaptive coping skills and self-efficacy may improve relations with others and autonomy among persons with MS.

Multiple sclerosis is associated with differences in semantic memory structure.

OBJECTIVE: Although language is often considered to be largely intact in multiple sclerosis (MS), word-finding difficulties are a common complaint. Recent work suggests that declines in language are not solely the result of motoric and cognitive slowing that is most strongly associated with MS. Network science approaches have been effectively used to examine network structure as it relates to clinical conditions, aging, and language. The present study utilizes a network science approach to investigate whether individuals with MS exhibit less interconnected and resilient semantic networks compared to age-matched neurotypical peers. METHOD: We used semantic fluency data from 89 participants with MS and 88 neurotypical participants to estimate and analyze the semantic network structure for each participant group. Additionally, we conducted a percolation analysis to examine the resilience of each network. RESULTS: Network measures showed that individuals with MS had lower local and global clustering coefficients, longer average shortest path lengths, and higher modularity values compared to neurotypical peers. Small-worldness, network portrait divergence measures, and community detection analyses were consistent with these results and indicated that macroscopic properties of the two networks differed and that the semantic network for individuals with MS was more fractured than the neurotypical peer network. Moreover, a spreading activation simulation and percolation analysis suggested that the semantic networks of individuals with MS are less flexible and activation degrades faster than those of age-matched neurotypical participants. CONCLUSIONS: These differing semantic network structures suggest that language retrieval difficulties in MS partially result from decline in language-specific factors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Associations between Social Support and Cognitive Performance among Persons with MS.

BACKGROUND: Social support is a protective factor against cognitive decline in the general population. However, the relationship between social support and cognitive functioning among persons with multiple sclerosis (MS) is not well understood. OBJECTIVE: The present study aimed to investigate the associations between different aspects of social support and cognitive performance among persons with MS. METHODS: A volunteer sample of 60 persons with MS completed the Medical Outcomes Study Support Social Survey 5-item short form (MSSS-5) and the Social Network Index (SNI). Cognitive functioning was assessed through a virtually-administered neuropsychological battery. Multiple linear regressions were conducted to examine the associations between social support measures and cognitive performance. RESULTS: In models adjusting for level of premorbid functioning, both perceived social support (i.e., to what extent one receives assistance from their social network; p = .002) and total size of social network (i.e., total number of people one regularly talks to; p = .002) were significant predictors of processing speed/executive functioning with moderate effect sizes. However, when we accounted for employment status in a post hoc analysis, the association between social network size and processing speed/executive functioning became statistically insignificant, while the relationship between perceived social support and processing speed/executive functioning remained significant (p = .002). CONCLUSIONS: Greater perceived social support is associated with better performance on processing speed/executive functioning measures among persons with MS, independent of effects from premorbid functioning and employment status. Maintaining a strong social support network may be an important factor in optimizing cognitive health in MS.

Unemployment in multiple sclerosis: the contribution of personality and disease.

BACKGROUND: Multiple sclerosis (MS) is the leading cause of neurological disability among young and middle-aged adults. One of the most devastating consequences of MS in this relatively young population group is unemployment. Although certain demographic and disease factors have been associated with employment, few studies have examined the contribution of person-specific factors, such as personality. OBJECTIVE: The goal of this study was to determine the extent to which personality, demographics, and clinical measures contribute to unemployment in MS. METHOD: A total of 101 individuals with MS who were enrolled in a clinical trial on cognition underwent a brief neuropsychological battery and completed questionnaires related to vocation, mood, fatigue, and personality. Neurological impairment was measured with the Expanded Disability Status Scale (EDSS). RESULTS: Employment status was related with disease duration, MS subtype, level of neurological impairment, fatigue, performance on measures assessing information processing speed (Symbol Digit Modalities Test (SDMT)), learning and memory (Selective Reminding Test), and the personality characteristic of persistence. Based on a forward logistic regression analysis, EDSS, SDMT, and persistence were the strongest predictors of employment status. CONCLUSIONS: These findings underscore the importance of personality on outcomes in MS and point to the need for more clinical attention and research in this area.

Keeping it together: The role of social integration on health and psychological well-being among individuals with multiple sclerosis.

Research indicates that people with multiple sclerosis (MS) are more likely to report poorer health and well-being than their peers without MS. Fortunately, it is also known that an individual's social and lifestyle factors play a great role on maintaining and promoting one's health and overall well-being. The present study aimed to examine the role that social integration and social support, in particular have on health and psychological well-being (PWB) among individuals with MS. One hundred and eighty three individuals with MS completed measures of social and lifestyle factors, personality, physical and mental health, MS disease symptomatology and PWB. Cross sectional, regression analyses were conducted to determine the role of social and other lifestyle factors (e.g., diet/exercise) on health and PWB. A subset of this sample (108) completed a follow-up assessment. Longitudinal analyses of this sample were also conducted. Consistent with previous findings, the presence of social integration and social support were significant predictors of health and PWB even when taking into account other lifestyle factors (i.e., diet/exercise, substance use, smoking), cardiovascular risk, demographics (i.e., gender, age, education, relationship status) and personality. The role of social integration and support on health and PWB is well established. Present findings confirmed these associations among individuals with MS. These findings suggest that social integration and social support should be a crucial part of MS management and that further interventional studies aimed at improving social integration and reducing social isolation are warranted in an effort to promote and maintain overall health and well-being.

Multiple Sclerosis Performance Test (MSPT): Normative study of 428 healthy participants ages 18 to 89.

BACKGROUND: The Multiple Sclerosis Performance Test (MSPT) is a self-administered, iPad®-based, computerized system for quantifying neuroperformance (cognition, upper and lower extremity motor function, and vision) in patients with multiple sclerosis (MS). OBJECTIVE: The goal of the study is to provide regression-based norms for the four MSPT test modules to adjust for the influence of demographic variables (age, education, and sex). METHODS: The MSPT was administered to 428 cognitively intact, healthy adults (ages 18 to 89 years). Participants were recruited to achieve a demographically stratified sample from four geographically diverse United States testing sites. RESULTS: The amount of shared variance in test performance accounted for by demographic variables was 18-23% for an upper extremity motor test, 31% for a walking speed test, 32% for a low contrast visual acuity test, and 48% for a cognitive test. All four test modules were significantly influenced by age (linear and non-linear effects) and education. Additionally, sex influenced performance on the cognitive and walking speed tests. CONCLUSION: This study provides regression-based equations that can enhance the clinical interpretation of MSPT scores by adjusting for the potential influences of age, education, and sex.

A Study Protocol for a Multisite Randomized Controlled Trial of an Intervention to Improve Outcomes After Spinal Cord Injury.

Background: The consequences of spinal cord injury (SCI) can place significant demands on an individual's coping mechanisms. Interventions to promote psychological adjustment and coping are often included in inpatient rehabilitation programs; however, following discharge, many individuals with SCI do not receive ongoing counseling or education about psychological adjustment to disability. Effective postacute treatment models are needed to help individuals with SCI build skills that help them adapt to the stresses associated with a chronic physical disability, alleviate the consequences of anxiety and depression, and enhance subjective well-being. Objectives: To describe the protocol for a randomized clinical trial (RCT) of a 6-week intervention designed to improve psychosocial outcomes after SCI. Methods: To test efficacy and replicability of the intervention, we designed a three-arm, multisite RCT with assessments conducted at six time points. Our primary hypothesis is that participants in the Group arm will report greater improvements in psychosocial outcomes than participants who complete the intervention individually via video (Individual arm) or those who do not receive the intervention (Control arm). We also hypothesize that participants in the Group arm will maintain greater improvements in psychosocial outcomes longer than those in the individual or control arms. Conclusion: Results of the RCT will be presented and published to professionals and consumers, and intervention training and materials will be made available upon request.

Relationship between sensory processing patterns, trait anxiety, and health-related quality of life in multiple sclerosis.

Sensory processing patterns may predict health-related quality of life. This study examined this relationship in persons with multiple sclerosis considering trait anxiety as a potential mediator. Participants (n = 94) completed the Adolescent/Adult Sensory Profile and other self-report measures at one time point. Sensory processing patterns were significantly associated with trait anxiety and health-related quality of life. Direct and indirect effects of sensory processing patterns were identified on physical health-related quality of life, and indirect effects were identified on mental health-related quality of life. Facilitating adaptive behavioral responses to sensory information may promote health-related quality of life in this population.

The role of language ability in verbal fluency of individuals with multiple sclerosis.

BACKGROUND: While cognitive deficits in memory and processing speed have been well-documented in individuals with multiple sclerosis (MS), language is largely considered to be intact. Verbal fluency deficits observed in MS are often attributed to impaired processing speed and executive functions rather than language ability. The current study evaluates the contribution of various cognitive factors to verbal fluency including language ability, oral-motor speed, processing speed, and executive functions. METHODS: We analyzed pre-existing data from seventy-four (74) individuals with MS who completed a battery of neuropsychological tests designed to assess individual ability for various cognitive factors. We conducted linear multiple regression analyses with letter and category verbal fluency as outcome variables and performance on other cognitive domains (e.g., processing speed, executive functioning) as predictors. RESULTS: Both vocabulary and processing speed predicted letter fluency while only vocabulary predicted category fluency. These findings suggest that the observed verbal fluency deficits in MS may reflect both impaired language ability and processing speed. CONCLUSION: We propose that further research on language ability in MS is needed to determine if comprehensive neuropsychological test batteries for persons with MS should include tests of language ability to fully understand the cognitive profile of any given patient. Given the importance of language ability, it may be necessary to conduct a more thorough assessment of language in individuals with MS who experience a deficit in this domain.

The adapted symbol digit modalities test: Examining the impact of response modality.

BACKGROUND: Information processing speed is often impaired in neurological disorders, as well as with healthy aging. Thus, being able to accurately assess information processing speed is of high importance. One of the most commonly used tests to examine information processing speed is the Symbol Digit Modalities Test (SDMT), which has been shown to have good psychometric properties. OBJECTIVES: The current study aims to examine differences between two response modalities, written and oral, on the performance of an adapted version of the Symbol Digit Modalities Test. METHODS: Ninety-nine individuals completed two alternate forms of the adapted version of the SDMT (aSDMT). Participants were instructed to complete the five lines of the task as quickly and accurately as possible. On one form participants were instructed to provide their response in writing and on the other one, orally. Form and response modality (oral vs. written) were counterbalanced to control for practice effects. RESULTS: On average, there was a significant difference between response modalities, such that participants needed more time to respond when the response modality was written. For both response modalities, time to complete each line of stimuli decreased as the task progressed. While changes in response time on the first four lines of stimuli on the oral version were not found, there was a substantial improvement in response time on the fifth line. In contrast, on the written version a gradual learning effect was observed, in which response time was the slowest on the first two lines, an intermediate response time was noted on line 3, and the fastest response time was achieved on lines four and five. CONCLUSION: The current study demonstrates that response modality, oral versus written, can significantly impact performance efficiency (the length of time it takes to complete a task), but not accuracy (total correct responses), on a new adaptation of the SDMT, the aSDMT.