Assessing multimodal emotion recognition in multiple sclerosis with a clinically accessible measure.

BACKGROUND: Multiple sclerosis (MS) negatively impacts cognition and has been associated with deficits in social cognition, including emotion recognition. There is a lack of research examining emotion recognition from multiple modalities in MS. The present study aimed to employ a clinically available measure to assess multimodal emotion recognition abilities among individuals with MS. METHOD: Thirty-one people with MS and 21 control participants completed the Advanced Clinical Solutions Social Perceptions Subtest (ACS-SP), BICAMS, and measures of premorbid functioning, mood, and fatigue. ANCOVAs examined group differences in all outcomes while controlling for education. Correlational analyses examined potential correlates of emotion recognition in both groups. RESULTS: The MS group performed significantly worse on the ACS-SP than the control group, F(1, 49) = 5.32, p = .025. Significant relationships between emotion recognition and cognitive functions were found only in the MS group, namely for information processing speed (r = 0.59, p < .001), verbal learning (r = 0.52, p = .003) and memory (r = 0.65, p < 0.001), and visuospatial learning (r = 0.62, p < 0.001) and memory (r = 0.52, p = .003). Emotion recognition did not correlate with premorbid functioning, mood, or fatigue in either group. CONCLUSIONS: This study was the first to employ the ACS-SP to assess emotion recognition in MS. The results suggest that emotion recognition is impacted in MS and is related to other cognitive processes, such as information processing speed. The results provide information for clinicians amidst calls to include social cognition measures in standard MS assessments.

Cognition and Cognitive Fatigability: Association with Employment Status in Multiple Sclerosis.

BACKGROUND: Slowed processing speed impacts employment status in people with multiple sclerosis (PwMS). Studies on the Multiple Sclerosis Functional Composite (MSFC), which includes the Paced Auditory Serial Addition Test (PASAT), have demonstrated that the combined score predicts employment status. Whether PASAT performance alone is associated with employment status is less clear. In addition, no studies have yet evaluated whether cognitive fatigability (CF), as measured with the PASAT, is associated with employment status. The aim of the current study was to examine the association between PASAT performance, CF, and employment status in PwMS. METHODS: Hundred and eighty-six PwMS completed the PASAT as part of a larger neuropsychological battery. ANOVAs and chi-squares analyzed group differences between employed and unemployed participants with respect to demographics, PASAT performance scores, and CF. Linear regression determined whether PASAT performance and/or CF scores were associated with employment status. RESULTS: After controlling for demographic influences, group differences were noted between employed vs. unemployed individuals on PASAT performance scores only. Employment status was associated with PASAT performance scores but not CF. CONCLUSIONS: The current study confirmed that PASAT performance is associated with employment status in MS. Given that CF was not associated, it seems difficulties with information processing speed (IPS) and working memory have more impact on a PwMS's ability to remain employed rather than within-task performance decline.

Development of a behavioural intervention for cognitive fatigability in multiple sclerosis: Protocol for a pilot and feasibility study.

Background: Up to 90% of people with multiple sclerosis (PwMS) subjectively report fatigue as one of their worst symptoms. Fatigability is an objectively measured component of fatigue. Cognitive fatigability (CF) is a breakdown in task performance following sustained cognitive effort. There is a paucity of interventions targeting CF in MS. The prior success of behavioural interventions at improving subjective fatigue suggests that their adaptation may yield similar results for CF. Given the relationship between CF, sleep quality, and mood, a behavioural intervention targeting these factors, such as cognitive behavioural therapy (CBT), is warranted. Given the multidimensional nature of fatigue, a multifaceted approach targeting lifestyle factors and coping (e.g., fatigue management education supplemented by CBT for insomnia and exercise) might prove efficacious. Aim: We describe a protocol for a pilot feasibility study to design and implement a multi-dimensional behavioural intervention to improve CF in PwMS. Methods: Stage 1: development of a multi-dimensional group-based videoconference-delivered behavioural intervention based on a previously successful fatigue management program for PwMS. A facilitator manual will be drafted. Course material will focus on four themes: body (sleep and physical activity), mood (impact of depression and anxiety), mind (cognitive contributions), and context (pacing and communication). Stage 2: a needs assessment survey will be completed by 100 PwMS for input on what factors are important contributors to their CF. Modifications will be made to the course material and manual. Stage 3: the facilitator-delivered intervention will include 20 PwMS. After baseline assessment, participants will attend weekly 70-min videoconference group sessions for 8 weeks, including homework assignments. Follow-up assessment will re-evaluate outcomes. Stage 4: analysis and dissemination of results. The primary outcome is improvement in CF. Additional feasibility outcomes will determine if a randomized control trial (RCT) is pursued. Stage 5: refine the intervention based on outcomes and feedback from participants. Determining which aspects participants felt were most effective will help inform RCT design. Conclusion: The long-term goal is to ensure that PwMS have access to effective interventions in real-world settings to improve quality of life and enhance their ability to participate in cognitively demanding activities that they enjoy.

The symbol digit modalities test and the paced auditory serial addition test involve more than processing speed.

BACKGROUND: Slowed processing speed is the most frequently reported cognitive deficit for people with multiple sclerosis (MS). However, measures used to assess processing speed may also recruit other cognitive abilities. The present objective was to determine the contributions of different cognitive functions to performance on two commonly used processing speed measures: the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). METHODS: Adults with relapsing-remitting MS (n = 70) and controls (n = 72) completed the SDMT, PASAT, and multiple measures assessing processing speed, working memory, and learning. Hierarchical regression analyses were used to examine the contributions of MS, processing speed, working memory, learning, and all possible interactions among factors to SDMT and PASAT scores. RESULTS: Processing speed and working memory generally contributed to performance on the SDMT and PASAT, with learning additionally contributing to SDMT performance. However, significant interactions revealed processing speed did not influence PASAT performance for individuals with high working memory ability whereas processing speed became increasingly more important as working memory declined to average and low levels. Further, processing speed was associated with SDMT performance for patients with MS but not controls. CONCLUSIONS: These findings support a multifactorial interpretation of the SDMT and PASAT, which facilitates their usefulness as screening measures for cognitive decline but prevents them from identifying which specific cognitive functions are affected.

Validity and sensitivity of Canadian normative data for the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) battery.

BACKGROUND: Canada is amongst the countries with the highest rates of multiple sclerosis (MS). Given cognitive deficits can occur in up to 70% of individuals with MS, there is a need for Canadian normative data that allows clinicians and researchers to evaluate cognitive impairment. Discrete and regression-based Canadian normative data for the Minimal Assessment of Cognitive Function in MS (MACFIMS) was recently published. The current study sought to evaluate the discriminant and predictive ability of these norms in a Canadian MS sample. METHODS: 188 individuals with a confirmed diagnosis of MS and 174 matched healthy controls completed all, or some, of the MACFIMS battery. RESULTS: Individuals with MS performed worse than healthy controls on most MACFIMS measures to a significant degree. Similarly, a greater frequency of impairment was also observed on each measure in the MS group. When defining global impairment as ≤ - 1.5 standard deviations below the mean on at least 2 or more tests, the MACFIMS battery identified cognitive impairment in 41.49% of the Canadian MS sample. Area under the curve analyses showed acceptable discriminatory ability for most of the measures. No difference in the sensitivity at detecting cognitive impairment was observed when comparing the discrete vs. the regression-based Canadian norms. CONCLUSION: The MACFIMS was able to detect cognitive impairment in a Canadian MS sample and can discriminate between individuals with MS and healthy controls when using Canadian norms. The validation of these norms will allow clinicians and researchers to evaluate cognitive impairment using more culturally-appropriate comparisons for Canadians living with MS.

Mesenchymal stem cell therapy and cognition in MS: Preliminary findings from a phase II clinical trial.

BACKGROUND: Mesenchymal stem cell (MSC) therapies are being evaluated in multiple sclerosis (MS) for possible neural repair. To date, the potential benefits on cognition have received little attention. The objective of the current study was to comprehensively evaluate cognition before and after MSC therapy in those with MS as part of a double-blind, phase II clinical trial. METHODS: Twenty-eight individuals with a confirmed diagnosis of MS were randomly assigned into two study arms. Cognition was evaluated using an expanded Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. The battery was administered at Week 0, Week 24, and Week 48 and results were analysed at the group and individual level. RESULTS: No detectable effect of MSC-mediated neural repair was noted in the short-term with respect to cognition, although some cognitive stability or improvement was observed. Decline was noted in some cognitive areas immediately following the procedure at Week 24; though these were temporary with performance returning to baseline levels at Week 48. CONCLUSIONS: While MSC therapy does not lead to improvement in cognition, at least in the short-term, neither does the procedure have lasting deleterious effects. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for individuals with MS.

Validation of Discrete and Regression-Based Performance and Cognitive Fatigability Normative Data for the Paced Auditory Serial Addition Test in Multiple Sclerosis.

Cognitive fatigability is an objective performance decrement that occurs over time during a task requiring sustained cognitive effort. Although cognitive fatigability is a common and debilitating symptom in multiple sclerosis (MS), there is currently no standard for its quantification. The objective of this study was to validate the Paced Auditory Serial Addition Test (PASAT) discrete and regression-based normative data for quantifying performance and cognitive fatigability in an Ontario-based sample of individuals with MS. Healthy controls and individuals with MS completed the 3″ and 2″ versions of the PASAT. PASAT performance was measured with total correct, dyad, and percent dyad scores. Cognitive fatigability scores were calculated by comparing performance on the first half (or third) of the task to the last half (or third). The results revealed that the 3″ PASAT was sufficient to detect impaired performance and cognitive fatigability in individuals with MS given the increased difficulty of the 2″ version. In addition, using halves or thirds for calculating cognitive fatigability scores were equally effective methods for detecting impairment. Finally, both the discrete and regression-based norms classified a similar proportion of individuals with MS as having impaired performance and cognitive fatigability. These newly validated discrete and regression-based PASAT norms provide a new tool for clinicians to document statistically significant cognitive fatigability in their patients.

Cognitive fatigability in multiple sclerosis: How does performance decline over time on the Paced Auditory Serial Addition Test?

BACKGROUND: Cognitive fatigability (CF) can be defined as an inability to maintain an optimal level of performance throughout a sustained cognitive task. It remains unclear, however, whether there is a specific moment during a cognitive task, such as the Paced Auditory Serial Addition Test (PASAT), when performance begins to break down. Thus, the present study aimed to evaluate how performance declines over time on the PASAT in people with multiple sclerosis (PwMS) compared to healthy controls. METHODS: 178 PwMS and 186 control participants were administered the 3" and 2" PASAT as part of a larger battery of neuropsychological tests. To examine how CF differed between the groups, repeated measures ANOVAs were used to evaluate the cumulative error rates made by each group throughout the task. In addition, how the error rate developed across the task on each trial was examined to evaluate in more detail the difference between groups with respect to how performance declined from the beginning to the end of the task. Lastly, exploratory two-way independent sample ANOVAs examined whether there was an influence of stimulus complexity (single vs. double-digit answers) on task performance. RESULTS: Compared to healthy controls, PwMS produced a greater number of errors overall on the PASAT and demonstrated more vulnerability to CF than healthy controls, as reflected by a greater number of errors made towards the end of the task. This difference was more noticeable on the 3" PASAT, given the difficulty both groups experienced on the 2" form. On the 3" PASAT, by Trial 37, PwMS had made significantly more cumulative errors than controls, however the rate of error generation was largely consistent and linear from the beginning to the end. Some of the group differences observed may be partially attributable to stimulus complexity influencing task performance. CONCLUSIONS: The 3" PASAT is more sensitive to group differences in CF and error generation than the 2" PASAT. With respect to CF, the greater vulnerability observed in the MS group is not due to a breakdown in performance or an increase in the rate of error generation at any specific point during the task; rather there is a linear decline in performance from the start. These results suggest that PwMS struggle to maintain optimal performance during sustained cognitive effort from the very beginning and demonstrate a steeper, but steady, rate of decline over time.

Increasing the Clinical Utility of the Paced Auditory Serial Addition Test: Normative Data for Standard, Dyad, and Cognitive Fatigability Scoring.

BACKGROUND: No normative data currently exist that would allow clinicians to decide whether the degree of cognitive fatigability (CF) experienced in individuals with neurologic disease is greater than expected when compared with a healthy population. OBJECTIVE: To establish discrete and regression-based normative data for CF as defined by an objective decrement in performance over the course of a cognitive task; namely, the Paced Auditory Serial Addition Test (PASAT). In addition, to develop discrete and regression-based normative data for PASAT performance scores-dyad and percent dyad-for which data do not currently exist. METHOD: One hundred and seventy-eight healthy individuals completed the PASAT as part of a larger neuropsychological battery. PASAT performance scores including total correct responses, total dyads, and percent dyad were calculated. CF scores were calculated by comparing the individuals' performance on the first half (or third) of the test to their performance on the last half (or third) in order to capture any within-task performance decrements over time. RESULTS: Both age- and education-based discrete normative data and demographically adjusted (sex, age, and education) regression-based formulas were established for the PASAT performance scores and the CF scores. CONCLUSION: The development of these normative data will allow for greater interpretation of an individual's performance on the PASAT, beyond just the total correct score, through the use of dyad and percent dyad scores. With respect to CF, these data will allow clinicians to objectively quantify decrements in cognitive performance over time better in individuals with neurologic diseases.

The relationship between neurofilament light chain and cognition in neurological disorders: A scoping review.

Neurofilament light chain (NfL) is an emerging biomarker of neural degeneration. NfL is an integral component of axons and is released into the bloodstream and cerebrospinal fluid during neurodegeneration; hence it can be used to monitor disease progression. Given that several neurological disorders are accompanied by cognitive decline, recent literature has investigated the relationship between NfL levels and cognition. The objective of this scoping review was to determine whether a consistent relationship between NfL and cognition exists in the context of variable degrees of neurodegeneration present across several neurological disorders. Four electronic databases were searched for relevant articles and 160 articles were initially identified. After article screening, 37 studies met the final inclusion criteria. Studies were then qualitatively synthesized to determine the relationship between NfL and cognition across a variety of neurological disorders. The large majority of studies found that NfL levels are inversely correlated with cognition, such that higher NfL levels are associated with poorer cognition. This relationship was not universal, however, and this discrepancy was speculated to be due to the nature of the neurological disorder, individual differences between participants, or methodological inconsistencies. Further study is required, and associated recommendations were proposed for the design of future investigations.

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis.

OBJECTIVE: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. METHODS: Sera were collected from 22 MS patients pre- and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. RESULTS: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). INTERPRETATION: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

Imaging cognitive fatigability in multiple sclerosis: objective quantification of cerebral blood flow during a task of sustained attention using ASL perfusion fMRI.

Cognitive fatigability (CF) can be defined as an inability to maintain performance throughout a sustained cognitive task. Individuals with multiple sclerosis (MS) are more susceptible to CF than healthy controls (HCs); however, the neural correlates underlying CF are still under investigation. Arterial spin labeling (ASL) perfusion imaging provides a non-invasive method of objectively quantifying cerebral blood flow (CBF) during sustained attention tasks. To date, no study has yet evaluated CF in MS using this methodology. 10 MS and 10 HCs completed a 20-min psychomotor vigilance task (PVT). CF was evaluated by dividing the PVT into quintiles and examining performance from the 1st to the last. Mean reaction times (RTs) and number of lapses were recorded. Global and regional CBF changes were evaluated throughout the PVT as well as during pre- and post-task rest. Increased susceptibility to CF was noted in the MS group. Distinct patterns of CBF activation were observed in areas comprising fronto-parietal, cortico-striatal, cerebellar, and basal ganglia regions; however, when and how these regions were engaged differed between the MS and HC groups. In particular, dysfunction in CBF to the middle frontal gyrus may underlie the CF effects observed. In addition, individuals with MS appear to struggle with "switching off" regions of the attentional network at rest following sustained cognitive effort. Findings support the use of ASL as an appropriate methodology for evaluating CF in MS with an overall pattern of attentional network dysfunction being observed. Objectively quantifying CF in this manner can help validate patients' subjective complaints.

Cognitive Fatigability Interventions in Neurological Conditions: A Systematic Review.

INTRODUCTION: Although fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions. METHODS: In accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion. RESULTS: The search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One study utilized a procedural intervention (i.e. transcranial direct current stimulation), while the other utilized a pharmacological intervention (i.e. fampridine-SR). Studies were evaluated for risk of bias, and evidence from both eligible studies was discussed. CONCLUSION: Despite the positive results of the procedural intervention, the paucity of eligible studies and the nascent nature of the field suggests that more studies are required before firm conclusions can be drawn regarding the amenability of CF to treatment. TRIAL REGISTRATION: The review was registered with PROSPERO (CRD42019118706).

Predictive Models of Cognitive Fatigue in Multiple Sclerosis.

OBJECTIVE: Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The present study examined the interrelatedness of disease severity, fatigue, depression, and sleep quality in order to evaluate their predictive roles of CF in MS. Four theoretical models examining these variables were assessed. METHODS: Fifty-eight individuals with a diagnosis of MS were recruited. CF was measured by examining last third versus first third performance on the Paced Auditory Serial Addition Test (PASAT). The PASAT and self-report measures of fatigue, depression, and sleep quality were administered. Path analysis was used to evaluate each of the models. RESULTS: CF was correlated only with depression (r = .362, p = .006) and sleep quality (r = .433, p = .001). Sleep quality was the greatest significant independent predictor of CF (ß = .433, t(1,55) = 3.53, p < .001), accounting for 17.3% of the total variance. The best fitting model showed sleep quality as the largest contributor to CF; however, depression played a smaller predictive role. Furthermore, depression emerged as the strongest predictor of sleep quality and fatigue. Disease severity weakly predicted depression. CONCLUSIONS: Sleep quality is the most significant predictor of CF in MS. As such, sleep quality may be a treatable cause of CF. Sleep quality itself, however, accounted for only 17.3% of the variance in CF suggesting that other variables which were not formally assessed in this sample (e.g., anxiety, etc.) may also play a predictive role. Follow-up studies should evaluate how results may differ with a larger sample size.

Longitudinal Stability of Cognition in Early-Phase Relapsing-Remitting Multiple Sclerosis: Does Cognitive Reserve Play a Role?

BACKGROUND: Up to 70% of people with multiple sclerosis (MS) experience cognitive impairment. Some remain cognitively intact despite advanced disease. Cognitive reserve (CR) theory postulates that individuals with higher levels of intellectual enrichment can tolerate more pathology than others before exhibiting cognitive impairment. METHODS: Thirty-two individuals with early-phase relapsing-remitting MS with mild physical disability and disease duration less than 10 years and 32 controls were recruited. At baseline and after 3 years, participants completed neuropsychological tests evaluating several cognitive domains. The CR was assessed via a cognitive reserve index (CRI) using educational levels and North American Adult Reading Test scores. Change in cognition was assessed using a reliable change index. RESULTS: At baseline, people with MS performed worse than controls on visual memory. There were no significant group differences on information processing speed, learning, language, and executive functions. Most cognitive domains showed no change over time, and CRI was not a significant predictor in the regression model. CONCLUSIONS: People with MS performed worse on memory tasks at baseline compared with controls. Cognitive change differed between people with MS and controls in executive functions. Although people with MS and controls improved over time, beyond practice effects, people with MS improved less than controls. Overall, no cognitive deterioration was noted over time, and CR did not predict change in cognition. Sample homogeneity in terms of disease stage and CR may explain these findings.

A Longitudinal Evaluation of Cognitive Fatigue on a Task of Sustained Attention in Early Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cognitive fatigue can be objectively measured on tasks of sustained attention and can be defined as decreased performance as a result of sustained cognitive effort. Individuals with multiple sclerosis (MS) early in their disease are vulnerable to cognitive fatigue, although this has yet to be evaluated longitudinally. We aimed to evaluate cognitive fatigue over a 3-year interval in individuals with early-phase relapsing-remitting MS (RRMS). The sensitivity of the Paced Auditory Serial Addition Test (PASAT) at detecting cognitive fatigue was evaluated, as was the impact of scoring method. METHODS: 32 people with MS and 32 controls completed the 3- and 2-second PASAT (PASAT-3″ and -2″) as a measure of sustained attention at baseline and 3-year follow-up. RESULTS: Performance on the PASAT remained stable across time, with improvement noted on the PASAT-2″ likely due to practice and the small sample size. Cognitive fatigue was noted at both times, although sensitivity varied based on scoring method. No evidence of worsening cognitive fatigue was noted over time. The MS group performed worse only when cognitive fatigue was the outcome variable. CONCLUSIONS: Although individuals with MS continue to be vulnerable to cognitive fatigue at follow-up, severity does not seem to increase with time. Cognitive fatigue may be a more sensitive marker of cognitive impairment than overall task performance in those with early-phase RRMS, which has important implications given that clinically only task performance is typically assessed.

Canadian Normative Data for Minimal Assessment of Cognitive Function in Multiple Sclerosis.

OBJECTIVE: The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus-based collection of neuropsychological tests that evaluate cognitive functioning in individuals with multiple sclerosis (MS). The tests are typically scored using each respective published test manual, leaving the examiner to make interpretations from norms derived from different American populations. Given demographic differences, this may lead to misinterpretation of findings in Canadians. Our goal was to establish both discrete and regression-based normative data for the MACFIMS based on a largely co-normed Canadian population to allow for improved psychometric interpretation. METHODS: MACFIMS data sets were aggregated from across three different Canadian cities (Ottawa, Toronto, and London), yielding a total of 330 healthy control participants from four different studies evaluating cognition in individuals with MS. Given the variety of contributing studies, there was variability in terms of the number of participants completing each measure. RESULTS: Both age-based discrete normative data and demographically adjusted (sex, age, and education) regression-based formulae were established. The demographic variables varied in their contribution to each MACFIMS test in the regression models, predicting 0 to 18% of the variance. CONCLUSIONS: Provision of these regression-based formulae will allow for more accurate interpretation of Canadian-derived MACFIMS scores by allowing clinicians to correct for all relevant demographic variables simultaneously, leading to improved clinical decision making for individuals with multiple sclerosis.

Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS): Canadian contribution to the international validation project.

BACKGROUND: Given the high prevalence of cognitive dysfunction in people with multiple sclerosis (PWMS) and the lack of availability of specialized neuropsychological services in most MS Clinics, there is a need for a brief cognitive monitoring tool that can be easily administered by MS clinic staff. OBJECTIVE: We aimed to establish the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) as a feasible cognitive monitoring tool and provide Canadian data toward the international validation effort. Secondary considerations were to determine if BICAMS correlates with self-reported cognition and predicted vocational status. METHODS: 57 PWMS were matched to 51 healthy controls (age, sex, education). Participants completed the BICAMS battery which includes the Symbol Digit Modalities Test, and the learning trials from the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. Depression, self-reported cognition, and fatigue were assessed. Participants were re-tested 15.6 (SD 2.0) days later. RESULTS: With impairment defined as "one or more abnormal tests," 57.9% of MS sample was cognitively impaired. Participants were more likely to be impaired on the BVMT-R (43.9%). On the SDMT and CVLT-II, 28.1% and 26.3% of MS participants were impaired. Sensitivity and specificity were highest for the SDMT. The BICAMS was reliable over time (r value range from 0.69 for BVMT-R to 0.87 for SDMT) with the SDMT being most robust. There was no relationship between BICAMS and subjective cognition. The BVMT-R reliably predicted employment. CONCLUSIONS: The BICAMS detected cognitive impairment to a comparable degree to more comprehensive neuropsychological batteries and is a valid measure of cognition in MS. Reliability of components varies, suggesting care be taken when interpreting serial testing results. The BICAMS is a feasible cognitive assessment tool in Canadians and yields comparable results to other cultures.

Cognitive fatigue in individuals with multiple sclerosis undergoing immunoablative therapy and hematopoietic stem cell transplantation.

BACKGROUND: Fatigue presents as a significant problem in multiple sclerosis (MS). Cognitive fatigue (CF) can be defined as a decrease in, or inability to maintain task performance throughout the duration of a continuous cognitive task. CF was evaluated using the Paced Auditory Serial Addition Test (PASAT) both pre- and post-immunoablation and hematopoietic stem cell transplantation (IA-HSCT) over a 3-year follow-up period. The magnitude of CF was examined and the impact of scoring methodology was evaluated. METHODS: Twenty-three individuals with rapidly progressive MS and poor prognosis underwent high dose immunosuppression and subsequent HSCT. Individuals completed the 3″ and 2″ PASAT at baseline and every 6 months thereafter over a period of 36 months. As scoring methodology can impact its sensitivity to CF, the PASAT was scored according to three scoring methods. RESULTS: CF was noted across all three scoring methods at baseline and at the majority of time points post-IA-HSCT on both the 3″ and 2″ PASAT. The magnitude of CF remained consistent both pre-and post-IA-HSCT. CONCLUSIONS: While results suggest that the procedure itself does not ameliorate an individual's susceptibility to CF; neither does it seem to negatively impact levels of CF. As such, results support the notion that the IA-HSCT procedure, despite its aggressive nature, does not exacerbate CF in this particular sample.

Cognition in early relapsing-remitting multiple sclerosis: consequences may be relative to working memory.

The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed,as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages.